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DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with AFRICURE PHARMA, ROW2TECH, NIPER-G, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India as ADVISOR, earlier assignment was with GLENMARK LIFE SCIENCES LTD, as CONSUlTANT, Retired from GLENMARK in Jan2022 Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 32 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 32 PLUS year tenure till date Feb 2023, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 100 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 100 Lakh plus views on dozen plus blogs, 227 countries, 7 continents, He makes himself available to all, contact him on +91 9323115463, email, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 38 lakh plus views on New Drug Approvals Blog in 227 countries...... , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc He has total of 32 International and Indian awards

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THIAMINE, Vitamin B1



  • Molecular FormulaC12H17N4OS
  • Average mass265.354 Da
  • Thiazolium, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-5-(2-hydroxyethyl)-4-methyl-, chloride, hydrochloride (1:1:1), Thiamine CL  hcl, 67-03-8, (Component: 70-16-6) 1;1;1,
  • C12 H17 N4 O S . Cl H . Cl

3595616 [Beilstein]


thiamin hydrochloride
Vitamin B1 hydrochloride
thiamine hydrochloride
aneurin hydrochloride
3-(4-amino-2-methyl-5-pyrimidinyl)methyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride hydrochlorideThiamineCAS Registry Number: 59-43-8CAS Name: 3-[(4-Amino-2-methyl-5-pyrimidinyl)methyl]-5-(2-hydroxyethyl)-4-methylthiazolium chlorideAdditional Names: vitamin B1; aneurin; thiamine monochloride; thiaminium chlorideMolecular Formula: C12H17ClN4OSMolecular Weight: 300.81Percent Composition: C 47.91%, H 5.70%, Cl 11.79%, N 18.63%, O 5.32%, S 10.66%Literature References: Essential nutrient required for carbohydrate metabolism; also involved in nerve function. Biosynthesized by microorganisms and plants. Dietary sources include whole grains, meat products, vegetables, milk, legumes and fruit. Also present in rice husks and yeast. Converted in vivo to thiamine diphosphate, a coenzyme in the decarboxylation of a-keto acids. Chronic deficiency may lead to neurological impairment, beriberi, Wernicke-Korsakoff syndrome. Isoln from rice bran: B. C. P. Jansen, W. F. Donath, Chem. Weekbl.23, 201 (1926). 
Structure: R. R. Williams, J. Am. Chem. Soc.58, 1063 (1936); R. R. Williams, J. K. Cline, ibid. 1504; R. R. Williams et al.,ibid.59, 526 (1937). Review of syntheses: Knobloch in H. Vogel, Chemie und Technik der Vitaminevol. II (Stuttgart, 1953) pp 1-128. Toxicity data: D. Winter et al.,Int. Z. Vitaminforsch.37, 82 (1967). HPLC determn in foods, pharmaceuticals, body tissues: T. Kawaski, Methods Enzymol.122, 15 (1986); in plasma and pharmacokinetics: H. Mascher, C. Kikuta, J. Pharm. Sci.82, 56 (1993). 
Review of bioavailability, absorption, and role in nutrition: F. L. Iber et al.,Am. J. Clin. Nutr.36, 1067-1082 (1982). Reviews: “Thiamin: Twenty Years of Progress”, Ann. N.Y. Acad. Sci.378, H. Z. Sable, C. J. Grubier, Eds. (1982) 470 pp; “Thiamin, Vitamin B1, Aneurin” in Vitamins, W. Friedrich, Ed. (de Gruyter, Berlin, 1988) pp 339-401. 
Derivative Type: HydrochlorideCAS Registry Number: 67-03-8Additional Names: Thiamine chloride hydrochloride; thiamine dichlorideTrademarks: Benerva (Roche); Betabion (Merck KGaA); Betalin S (Lilly); Betaxin (Sterling Winthrop); Bewon (Wyeth); Metabolin (Takeda); Vitaneurin (Mepha)Molecular Formula: C12H17ClN4OS.HClMolecular Weight: 337.27Percent Composition: C 42.73%, H 5.38%, Cl 21.02%, N 16.61%, O 4.74%, S 9.51%Literature References: Comprehensive description: K. A. M. Al-Rashood et al.,Anal. Profiles Drug Subs.18, 413-458 (1989).Properties: Monoclinic plates in rosette-like clusters. Slight thiazole odor. Bitter taste. dec 248°. One gram dissolves in ~1 ml water, 18 ml glycerol, 100 ml 95% alcohol, 315 ml abs alcohol; more sol in methanol. Sol in propylene glycol. Practically insol in ether, benzene, hexane, chloroform. pH of a 1% w/v soln in water 3.13; pH of a 0.1% w/v soln in water 3.58. 
On exposure to air of average humidity, the vitamin absorbs an amount of water corresponding to nearly one mol, forming a hydrate. LD50 in mice (mg/kg): 89.2 i.v.; 8224 orally (Winter).Toxicity data: LD50 in mice (mg/kg): 89.2 i.v.; 8224 orally (Winter) 
Derivative Type: MononitrateCAS Registry Number: 532-43-4Molecular Formula: C12H17N5O4SMolecular Weight: 327.36Percent Composition: C 44.03%, H 5.23%, N 21.39%, O 19.55%, S 9.80%Literature References: Prepn: R. J. Turner, G. J. Schmitt, US2844579 (1958 to Am. Cyanamid).Properties: Crystals, mp 196-200° (dec). Practically nonhygroscopic. pKa 4.8. Soly in water (g/100 ml): 2.7 (25°); ~30 (100°). pH of 2% aq soln 6.5 to 7.1. More stable than the hydrochloride; suitable for enrichment of flours and feeds, multivitamin prepns.Melting point: mp 196-200° (dec)pKa: pKa 4.8 
Therap-Cat: Vitamin (enzyme cofactor).Therap-Cat-Vet: Vitamin (enzyme cofactor).Keywords: Enzyme Cofactor; Vitamin/Vitamin Source; Vitamin B1.

Vitamin B1 (Thiamine)

Deficiency of this causes beriberi

Vitamin B1 - spacefill model

Some symptoms of ‘dry’ beriberi
Some symptoms of ‘dry’ beriberi. There is also a ‘wet’ version of beriberi which mainly affects the heart and circulatory system,
with shortness of breath, swelling of the lower legs, and increased heart rate. 
According to the global “Vitamin B1 (Thiamine Mononitrate) Market 2020” research report, the global vitamin B1 market revenue was USD 648.8 million in 2020 and will be projected to reach USD 854.7 million by 2026.Global Vitamin B1 (Thiamine Mononitrate) Sales Market Report 2020, 2020. Fully Continuous Flow Synthesis of 3-Chloro-4-oxopentyl Acetate: An Important Intermediate for Vitamin B1
M Jiang, M Liu, C Yu, D Cheng… – … Process Research & …, 2021 – ACS Publications
… Journal Logo. Fully Continuous Flow Synthesis of 3-Chloro-4-oxopentyl Acetate:
An Important Intermediate for Vitamin B1. Meifen Jiang* Meifen Jiang. Shanghai
Engineering Center of Industrial Asymmetric Catalysis for Chiral … 

Compound Name:
Thiamin hydrochlorideMolecular Formula: C12H17ClN4OSMolecular Weight: 300.8CAS Registry No.:
67-03-8 MASS

13C NMR D2O 

1H NMR : 400 MHz in DMSO-d6


 The production device for the treatment drug thiamine hydrochloride for neuritis. The production process is as follows: add acetamidine hydrochloride and α-dimethoxymethyl-β-methoxymethylpropionitrile into the reactor D101, and condense in an alkaline medium Is 3,6-dimethyl 1,2-dihydro-2,4,5,7-tetrazine (Ⅱ), which is then hydrolyzed to obtain the intermediate product (Ⅲ), which is then closed to form 2-methyl in alkaline 4-amino-5-aminomethyl pyrimidine (IV), introduced into D102, continue to react with carbon disulfide and ammonia to obtain (Ⅴ), then condense with acetic acid-γ-chloro-γ propyl acetate, and then in hydrochloric acid After hydrolysis and cyclization, thiothiamine hydrochloride is obtained, which is pumped into D103, neutralized with ammonia water, oxidized by hydrogen peroxide, and then converted into ammonium nitrate thiamine with nitric acid, and finally hydrochloric acid is added to obtain the product. The invention has the advantages of reducing the intermediate links of the reaction, reducing the reaction temperature and the reaction time, and improving the reaction yield.

front page image

SYN Journal of Organic Chemistry, 54(16), 3941-5; 1989 





SYN fully continuous flow synthesis of 3-chloro-4-oxopentyl acetate (2), an important intermediate for vitamin B1 (1), was developed. This continuous flow manufacturing included two chemical transformations and an inline extraction step without intermediate purification and solvent exchange. In this work, the traditional synthetic route for batch operation was efficiently simplified via a series of separated screening tests in flows under various conditions. We found that the chlorination reaction can be carried out in only 30 s at room temperature by flow. We also simplified the decarboxylation/acylation step by using a cross-mixer, so that acetic anhydride was no longer required in the acylation reaction. A computational fluid dynamics simulation was carried out to study the improved micromixing of liquid–liquid two-phase streams. Finally, 3-chloro-4-oxopentyl acetate (2) was obtained in a 90% isolated yield with a product purity of 96% and a total residence time of approximately 32 min. This fully continuous process was operated smoothly for 12 h, and approximately 19.1 g of the desired product was generated with a production rate of 1.79 g h–1.

Abstract Image

Batch operation for the decarboxylation/acylation reaction Procedure: 1) Mix acetic acid (3.2 eq.), water (1.1 eq.), and 35 % hydrochloric acid (0.1eq.); 2) Add 1 eq. of 3-acetyl-3-chlorodihydrofuran-2(3H)-one (3) into the mixture at room temperature; 3) Increase the reaction temperature to 120 ℃ to reflux for about 2 hours; 4) Add 2 eq. of acetic anhydride to the mixture; 5) Keep reluxing for another 3 hours; 6) After reaction (analysed by GC-MS), add saturated sodium bicarbonate solution for neutralization to make the pH to be around 7; 7) Add DCM solvent to extract the product for 3 times; 8) Concentrate the DCM solution and distill under vacuum distillation to collect the highly pure product of 3-chloro-4-oxopentyl acetate (2). Distillation condition: 90 ℃, 3-7 mmHg. After 6 hours reaction,the yield of crude product is obtained as 63 % and the purity is around 92 %. After distillation, the purity increases to 95% with an isolation yield of 60%.The production rate for batch is about 1.47 g/h, which is less than the continuous process(1.79g/h). 




 Bulletin of the Chemical Society of Japan, 45(7), 2010-15; 1972

The reaction of 2-dimethoxymethyl-3-methoxypropionitrile (1) with acetamidine produces pyrimidopyrimidine (8via the consecutive process of 1→an intermediate→8. The intermediate was not isolated, but two structures have been proposed for it. We have now succeeded in the isolation of the intermediate and determined it to be 2-methyl-4-amino-5-dimethoxymethyl-5,6-dihydropyrimidine (4). Several key intermediates were also successfully isolated. The novel reaction pathway for the title reaction was concluded to be as follows: the elimination of methanol from 1, followed by the addition of acetamidine affords 3-acetamidinopropionitrile (3), the subsequent quick cyclization of which produces the intermediate, 4; the further elimination of methanol from 4, followed by a replacement reaction with acetamidine, gives an acetamidinomethylene compound (6), which is converted into the final product, 8via an intermediate (7). Some minor pathways will also be presented.




Synthesis of thiamine, method by Williams and Cline [90].

90 Williams, R.R. and Cline, J.K. (1936) Synthesis of vitamin B1. J. Am. Chem. Soc. 58, 1504–1505,

Thiaminpyrophosphate (11) (Figure 1) is an essential cofactor in all forms of life and it plays a key role in carbohydrate and amino acid metabolism by stabilizing acyl carbanion biosynthons. The mechanistic enzymology of thiamin pyrophosphate-dependent enzymes is described in detail in the chapter by Frank Jordan.1 Here, we will review recent progress on the biosynthesis of thiamin pyrophosphate in bacteria and Saccharomyces cerevisiae with an emphasis on some of the novel organic chemistry that has emerged from these studies. Recent reviews describing the regulation of the pathway,2,3 the identification of biosynthetic precursors,4 and the structural biology of the pathway5–7 have been published.


Vitamin B1 338 Commercial production involves a six-step synthetic procedure (Williams & Cline, 1936). Beginning with 339 ethyl 3-ethoxypropionate as the feedstock for vitamin B1 production, the synthetic reactions include (1) 340 formylation using ethyl formate, (2) reaction with acetamidine hydrochloride leading to aminopyrimidine 341 ring formation, (3) replacement of aminopyrimidine hydroxyl group with a chlorine atom (chlorination) 342 using phosphorus(V) oxychloride, (4) replacement of the labile chlorine atom with an amino group using 343 alcoholic ammonia, (5) ammonium salt formation using hydrobromic acid, (6) introduction of the thiazole 344 ring using 4-methyl 5-hydroxyethyl thiazole.

A search of the patent literature revealed two methods for vitamin B1 (thiamine) production by 349 fermentative methods. The first patent describes the development of mutants of the genus Saccharomyces 350 Meyen emend Reess (yeast) for synthesizing vitamin B1 from sugars and inorganic salts (Silhankova, 1980). A 351 more recent invention provides a method for producing thiamine products using a microorganism of the 352 genus Bacillus containing a mutation (i.e., gene deletions or other mutations) that causes it to overproduce 353 and release thiamine products into the medium (Goese, 2012).



The invention relates to the field of vitamin B1 synthesis, and particularly relates to a purification method of formyl pyrimidine and a synthetic method of vitamin B1. The purification method of formyl pyrimidine comprises the following steps: washing formyl pyrimidine with alcohol; washing formyl pyrimidine with water; dissolving formyl pyrimidine with alcohol, and decoloring formyl pyrimidine with activated carbon to obtain a formyl pyrimidine solution; and separating out formyl pyrimidine in the formyl pyrimidine solution and separating the formyl pyrimidine from the solution to obtain purified formyl pyrimidine. According to the purification method of formyl pyrimidine, by washing the formyl pyrimidine with alcohol and water, decoloring the formyl pyrimidine with activated carbon in an alcohol solution and separation the purification method of formyl pyrimidine by water, impurities in the formyl pyrimidine are removed, the content of the formyl pyrimidine reaches 99.5% over, and agood basis is provided for further synthesizing vitamin B1.

Example 1
        A method for purifying formyl pyrimidine, the steps are:
        a. Wash formyl pyrimidine with methanol to remove impurities dissolved in methanol in formyl pyrimidine. The weight ratio of formyl pyrimidine to methanol is 1:2.
        b. Add water to wash formyl pyrimidine to remove impurities dissolved in water in formyl pyrimidine. The weight ratio of formyl pyrimidine to water is 1:2.
        c. Dry the washed formylpyrimidine, add methanol at a weight ratio of 1:1, reflux and heat to 40-50°C to completely dissolve.
        d. Add activated carbon while hot for decolorization, the weight ratio of formylpyrimidine solution to activated carbon is 1:0.01, quickly stir and decolorize for 15min, and filter out formylpyrimidine solution while hot.
        e. Cool down to 0-10°C and formyl pyrimidine precipitates out, filter and dry to obtain formyl pyrimidine solid.
        The obtained formylpyrimidine solid was tested, as shown in Figure 1.
        The information in Figure 1 is shown in Table 1.
        Table 1 Detection peak information
        The formula for calculating the content of formyl pyrimidine in solid formyl pyrimidine is as follows:
        A—formylpyrimidine content;
        S 1 —Sample peak area;
        S 2 —Standard peak area;
        M 1 —Standard quality;
        M2—sample quality;
        W 1 —The concentration of the standard.
        According to calculation, the content of formyl pyrimidine purified by this method can reach 99.7%, and the content of formyl pyrimidine in the unpurified formyl pyrimidine is 91%.
        After testing, the yield was 94% based on the mass of the formyl pyrimidine before purification.
        The formyl pyrimidine obtained by the above purification method is reacted to obtain vitamin B1. Subsequent detection shows that the quality of vitamin B1 is higher, and the content of impurities in the detection data such as related substances and chromatographic purity is lower. The chromatographic purity of the impurity before purification was 0.8, and the chromatographic purity after purification was about 0.1. The content of each impurity in related substances decreased year-on-year. The average compliance rate of the final vitamin B1 is 100%.



1. 3-Mercapto-4-oxopentyl Acetate (5a). Anh. KSH (7.22 g, 0.1 mol) was suspended in 50 ml of abs. MeOH. The mixture was cooled to 0″ in an ice-bath and 3-chloro-4-oxopentyl acetate (3; 17.9 g, 0.1 mol), previously dissolved in 50 ml of abs. MeOH, was added dropwise in order to maintain the temp. in the mixture between 0 and 5″. After complete addition, stirring was continued at r.t. for 1 h, while a slow stream of N, was passed through the mixture to remove residual H2S. The precipitated KC1 was filtered off and the solvent evaporated under reduced pressure. The residue was taken up in 50 ml of CH,C12 and the insoluble material removed by filtration. Evaporation of the solvent in uamo at 30″ gave 14.9 g of slightly yellow liquid. Bulb-to-bulb distillation of the crude mixture at 120″/0.3 mm yielded 12.95 g (0.07 mol, 73.5%) of 5a as a colourless liquid7). IR (film): 2960w, 2550~. 1740s, 17153, 1370m, 1245s, 1050m. ‘H-NMR (CDCI,): 1.74 (d, J= 12, SH); 1.95-2.25 (m, CH,); 2.05 (s, AcO); 2.35(s,Me);3.42(td,J= 12,5.7,SCH);4.2(t,J=5.7,CH20).EI-MS: 134(2), 116(36),74(21),73(58),43(100). Anal. calc. for C7HI2O,S (176.23): C 47.71, H 6.86, S 18.19; found: C 47.94, H 6.95, S 17.24.

2. 3,4-Dihydro-7-methylpyrimido[4,5-d]pyrimidine (4). From 4-amino-2-methyl-5-(aminomethyl)pyrimidine (Za) and DMF-DMA. In a flask equipped with a Vigreux column and a Liebig condenser, Zag) (69 g, 0.5 mol) was suspended in dimethylformamide dimethyl acetal(59.6 g, 0.5 mol). The stirred suspension was slowly heated to ca. 8&85″, until the temp. at the head of the Vigreux column reached 60°9). The MeOH/Me,NH mixture was then distilled off, until the mixture in the flask became a thick mass. The temp. was increased to 90″ for 30 min, 250 ml of toluene were added, and the obtained suspension was further stirred for 1 h at 90°. It was then allowed to cool to r.t., filtered, and washed twice with 100 ml of hexane. The crude material was dried at SOo under reduced pressure: 69.6 g of a tan solid was obtained, which was then sublimated at 1 SOo (oil-bath temp.) under high vacuum (0.2 mm) togive65.5g(0.44mol,88.5%)of4asawhitesolid. M.p. 173″(dec.).UV:202(4),298(3,7).1R(KBr): 3430m(br.), 2860m, 2840s, 16703, 1620s, 15803, 15303, 1450s. 1210s. ‘H-NMR ((D,)DMSO): 2.4 (s, Me); 4.5 (s, CH,); 7.2 (br. s, vinyl. CH); 8.03 (s, arom. H); 9.9 (br. s, NH). EI-MS: 148 (50, M’), 147 (loo), 106 (12), 53 (17), 42 (20). Anal. calc. for C7H,N, (148.169): C 56.74, H 5.44, N 37.81; found: C 56.79, H 5.44, N 37.75.

From 2a and Triethyl Orthoformate. In a flask equipped with a 20-cm Vigreux column and a Liebig condenser, Zag) (69 g, 0.5 mol), triethyl orthoformate (148.2 g, 1 rnol), and TsOH (2.5 g)”) were introduced. The stirred suspension was slowly heated to ca. 110″ so that the temp. at the head of the Vigreux column reached 80-85″. The EtOH was then distilled off, until the mixture in the flask became a thick mass. The temp. was maintained at 100-1 10″ for 30 min, then 250 ml of toluene were added, and theobtained suspension was further stirred for 1 h at90°. It was cooled to r.t. and placed overnight in the refrigerator. The light-brown precipitate was filtered and washed twice with 50 ml of toluene. The crude material was dried at 50″ under reduced pressure to give 59.3 g of a beige solid which was sublimated at 150″ (oil-bath temp.) under high vacuuni (0.2 mm) to yield 52.5 g (0.35 mol, 71 %) of 4 as a white solid. M.p. 182O (dec.).

3. 3-1 (4-Amino-2-methylpyrimidin-5-yl)methyl]-5-(2-hydroxyethyl)-4-methylthiazolium Chloride Hydrochloride (Thiamine Hydrochloride, la). Compound 4 (7.4 g, 0.05 mol) was dissolved in 100 ml of HCOOH. To this slightly yellow soh, 5a (9.25 g, 0.052 mol) was immediately added at such a rate so that the temp. did not exceed 3540″. The mixture was further stirred for 30 min at r.t. and then 25 ml of a freshly prepared sat. soh. of HCI in abs. EtOH was added dropwise. The temp. rose to 35-36O, and the mixture was further stirred for 30 min at r.t.”), The crude mixture was then poured into a 500-ml flask and evaporated at 50″ under reduced pressure to give 26.07 g of a green-yellow solid residue, which was taken up in 100 ml of ahs. EtOH. Aq. HCI soh. (25%, 30 ml) was then added and the crude mixture heated on a steam-bath, until a clear soln. was obtained. The soln. was cooled to r.t. and placed overnight in the refrigerator. The resulting white crystals were collected and dried in vucuo to yield 14.56 g (86.3%) of la. M.p. 245-246′ (dec.). The mother-liquor was then evaporated at 50O under reduced pressure and the residue taken up in 50 ml of H,O. The aq. phase was then washed twice with 25 ml of CH2C1, and evaporated under reduced pressure to give 3.29 g of a still slightly greenish residue, which was again taken up in 20 ml of abs. EtOH. Aq. HCI soln. (25%, 5 ml) was added and the mixture heated on a steam-bath, until a clear soln. was obtained. It was then cooled to r.t. and kept overnight in the refrigerator. The white crystals were filtered to give 1.42 g (8.4%) of la. M.p. 244-24So(dec.) (combined yieldI2) of la: 94.7% based on 4).

Recrystallization. The two crops of la were combined and dissolved in 100 ml of warm abs. EtOH. Aq. HCI soh (25 %, 40 ml) was added. The soln. was then allowed to cool slowly to r.t. and kept at Oo overnight. The white crystals were filtered and dried in vucuo at 50″ to give 13.6 g (0.04 mol, 80.6 %) of la.

M.p. 243-244″ (dec.). UV: 234 (4.1), 266 (3.9).

IR (KBr): 3500m, 3430m. 3340m. 3240m. 3065s. 2615m. 1660s, 1607m, 1380m.

‘H-NMR (D,O): 2.54(s,Me);2.62(s,Me);3.19(t,J= 5.8,CH2);3.88(t,J= 5.8,CH20);5.56(s,1H,CH2N);8.02(s,1arom.H); proton of thiazole ring is exchanged with deuterium of D,O.

FAB-MS: 265 (100, M+), 181 (18), 144 (30), 123 (65), 122 (65), 91 (78).

Anal. calc. for C,2H18C1,N40S (337.27): C 42.74, H 5.38, N 16.61, S 9.51, CI 21.02; found: C 42.93, H 5.28, N 16.70, S 9.61, C121.17.


Thiamine, also known as thiamin or vitamin B1, is a vitamin found in food and manufactured as a dietary supplement and medication.[1][4] Food sources of thiamine include whole grainslegumes, and some meats and fish.[1] Grain processing removes much of the thiamine content, so in many countries cereals and flours are enriched with thiamine.[1][5] Supplements and medications are available to treat and prevent thiamine deficiency and disorders that result from it, including beriberi and Wernicke encephalopathy.[3] Other uses include the treatment of maple syrup urine disease and Leigh syndrome.[3] They are typically taken by mouth, but may also be given by intravenous or intramuscular injection.[3][6]

Thiamine supplements are generally well tolerated.[3][7] Allergic reactions, including anaphylaxis, may occur when repeated doses are given by injection.[3][7] Thiamine is in the B complex family.[3] It is an essential micronutrient, which cannot be made in the body.[8] Thiamine is required for metabolism including that of glucoseamino acids, and lipids.[1]

Thiamine was discovered in 1897, was the first B vitamin to be isolated in 1926, and was first made in 1936.[9] It is on the World Health Organization’s List of Essential Medicines.[10] Thiamine is available as a generic medication, and as an over-the-counter drug.[3]

Medical uses

Thiamine deficiency

Main article: Thiamine deficiency

Thiamine is used to treat thiamine deficiency which when severe can prove fatal.[11] In less severe cases, non-specific signs include malaise, weight loss, irritability and confusion.[12] Well-known disorders caused by thiamine deficiency include beriberiWernicke–Korsakoff syndromeoptic neuropathyLeigh’s diseaseAfrican seasonal ataxia (or Nigerian seasonal ataxia), and central pontine myelinolysis.[13]

In Western countries, thiamine deficiency is seen mainly in chronic alcoholism.[14] Thiamine deficiency is often present in alcohol misuse disorder. Also at risk are older adults, persons with HIV/AIDS or diabetes, and persons who have had bariatric surgery.[1] Varying degrees of thiamine deficiency have been associated with the long-term use of high doses of diuretics, particularly furosemide in the treatment of heart failure.[15]

Prenatal supplementation

See also: Prenatal vitamins

Women who are pregnant or lactating require more thiamine. For pregnant and lactating women, the consequences of thiamine deficiency are the same as those of the general population but the risk is greater due to their temporarily increased need for this nutrient. In pregnancy, this is likely due to thiamine being preferentially sent to the fetus and placenta, especially during the third trimester. For lactating women, thiamine is delivered in breast milk even if it results in thiamine deficiency in the mother.[16] Pregnant women with hyperemesis gravidarum are also at an increased risk for thiamine deficiency due to losses when vomiting.[17]

Thiamine is important for not only mitochondrial membrane development, but also synaptosomal membrane function.[18] It has also been suggested that thiamine deficiency plays a role in the poor development of the infant brain that can lead to sudden infant death syndrome (SIDS).[19]

Other uses

Thiamine is a treatment for some types of maple syrup urine disease and Leigh disease.[3]

Adverse effects

Thiamine is generally well tolerated and non-toxic when administered orally.[3] Rarely, adverse side effects have been reported when thiamine is given intravenously including allergic reactions, nausealethargy, and impaired coordination.[20][21]


Thiamine is a colorless organosulfur compound with an unpleasant sulfur odor and the chemical formula C12H17N4O S. Its structure consists of an aminopyrimidine and a thiazolium ring linked by a methylene bridge. The thiazole is substituted with methyl and hydroxyethyl side chains. Thiamine is soluble in watermethanol, and glycerol and practically insoluble in less polar organic solvents. As a base it can form salts with acids, such as hydrochloride. It is stable at acidic pH, but is unstable in alkaline solutions.[11][22] Thiamine, which is a persistent carbene, is used by enzymes to catalyze benzoin condensations in vivo.[23] Thiamine is unstable to heat, but stable during frozen storage.[24] It is unstable when exposed to ultraviolet light[22] and gamma irradiation.[25][26] Thiamine reacts strongly in Maillard-type reactions.[11]


A 3D representation of the TPP riboswitch with thiamine bound

Complex thiamine biosynthesis occurs in bacteria, some protozoans, plants, and fungi.[27][28] The thiazole and pyrimidine moieties are biosynthesized separately and then combined to form thiamine monophosphate (ThMP) by the action of thiamine-phosphate synthase (EC The biosynthetic pathways may differ among organisms. In E. coli and other enterobacteriaceae, ThMP may be phosphorylated to the cofactor thiamine diphospate (ThDP) by a thiamine-phosphate kinase (ThMP + ATP → ThDP + ADP, EC In most bacteria and in eukaryotes, ThMP is hydrolyzed to thiamine, which may then be pyrophosphorylated to ThDP by thiamine diphosphokinase (thiamine + ATP → ThDP + AMP, EC

The biosynthetic pathways are regulated by riboswitches.[21] If there is sufficient thiamine present in the cell then the thiamine binds to the mRNAs for the enzymes that are required in the pathway and prevents their translation. If there is no thiamine present then there is no inhibition, and the enzymes required for the biosynthesis are produced. The specific riboswitch, the TPP riboswitch (or ThDP), is the only riboswitch identified in both eukaryotic and prokaryotic organisms.[29]


Occurrence in foods

Thiamine is found in a wide variety of processed and whole foods. Whole grainslegumesporkfruits, and yeast are rich sources.[30][31]

The salt thiamine mononitrate, rather than thiamine hydrochloride, is used for food fortification, as the mononitrate is more stable, and does not absorb water from natural humidity (is non-hygroscopic), whereas thiamine hydrochloride is hygroscopic.[citation needed] When thiamine mononitrate dissolves in water, it releases nitrate (about 19% of its weight) and is thereafter absorbed as the thiamine cation.

Dietary recommendations

In the U.S. the Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for thiamine were updated in 1998, by the Institute of Medicine now known as the National Academy of Medicine (NAM).[32]

The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL defined the same as in United States. For women (including those pregnant or lactating), men and children the PRI is 0.1 mg thiamine per megajoule (MJ) of energy consumed. As the conversion is 1 MJ = 239 kcal, an adult consuming 2390 kilocalories should be consuming 1.0 mg thiamine. This is slightly lower than the U.S. RDA.[33] The EFSA reviewed the same safety question and also reached the conclusion that there was not sufficient evidence to set a UL for thiamine.[20]

United States
Age groupRDA (mg/day)Tolerable upper intake level[32]
Infants 0–6 months0.2*ND
Infants 6–12 months0.3*
1–3 years0.5
4–8 years0.6
9–13 years0.9
Females 14–18 years1.0
Males 14+ years1.2
Females 19+ years1.1
Pregnant/lactating females 14–501.4
* Adequate intake for infants, as an RDA has yet to be established[32]
European Food Safety Authority
Age groupAdequate Intake (mg/MJ)[20]Tolerable upper limit[20]
All persons 7 months+0.1ND

To aid with adequate micronutrient intake, pregnant women are often advised to take a daily prenatal multivitamin. While micronutrient compositions vary among different vitamins, a typical prenatal vitamin contains around 1.5 mg of thiamine.[34]

For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percentage of Daily Value (%DV). For thiamine labeling purposes 100% of the Daily Value was 1.5 mg, but as of 27 May 2016 it was revised to 1.2 mg to bring it into agreement with the RDA.[35][36] Compliance with the updated labeling regulations was required by 1 January 2020 for manufacturers with US$10 million or more in annual food sales, and by 1 January 2021 for manufacturers with lower volume food sales.[37][38] A table of the old and new adult daily values is provided at Reference Daily Intake.


Thiamine in foods can be degraded in a variety of ways. Sulfites, which are added to foods usually as a preservative,[39] will attack thiamine at the methylene bridge in the structure, cleaving the pyrimidine ring from the thiazole ring.[12] The rate of this reaction is increased under acidic conditions. Thiamine is degraded by thermolabile thiaminases (present in raw fish and shellfish).[11] Some thiaminases are produced by bacteria. Bacterial thiaminases are cell surface enzymes that must dissociate from the membrane before being activated; the dissociation can occur in ruminants under acidotic conditions. Rumen bacteria also reduce sulfate to sulfite, therefore high dietary intakes of sulfate can have thiamine-antagonistic activities.

Plant thiamine antagonists are heat-stable and occur as both the ortho- and para-hydroxyphenols. Some examples of these antagonists are caffeic acidchlorogenic acid, and tannic acid. These compounds interact with the thiamine to oxidize the thiazole ring, thus rendering it unable to be absorbed. Two flavonoids, quercetin and rutin, have also been implicated as thiamine antagonists.[12]

Food fortification

Main article: Food fortification

Refining grain removes its bran and germ, and thus subtracts its naturally occurring vitamins and minerals. In the United States, B-vitamin deficiencies became common in the first half of the 20th century due to white flour consumption. The American Medical Association successfully lobbied for restoring these vitamins by enrichment of grain, which began in the US in 1939. The UK followed in 1940 and Denmark in 1953. As of 2016, about 85 countries had passed legislation mandating fortification of wheat flour with at least some nutrients, and 28% of industrially milled flour was fortified, often with thiamine and other B vitamins.[40]

Absorption and transport


Thiamine is released by the action of phosphatase and pyrophosphatase in the upper small intestine. At low concentrations, the process is carrier-mediated. At higher concentrations, absorption also occurs via passive diffusion. Active transport is greatest in the jejunum and ileum, but it can be inhibited by alcohol consumption or by folate deficiency.[11] Decline in thiamine absorption occurs at intakes above 5 mg/day.[41] On the serosal side of the intestine, discharge of the vitamin by those cells is dependent on Na+-dependent ATPase.[12]

Bound to serum proteins

The majority of thiamine in serum is bound to proteins, mainly albumin. Approximately 90% of total thiamine in blood is in erythrocytes. A specific binding protein called thiamine-binding protein (TBP) has been identified in rat serum and is believed to be a hormone-regulated carrier protein important for tissue distribution of thiamine.[12]

Cellular uptake

Uptake of thiamine by cells of the blood and other tissues occurs via active transport and passive diffusion.[11] About 80% of intracellular thiamine is phosphorylated and most is bound to proteins. Two members of the SLC gene family of transporter proteins, SLC19A2 and SLC19A3, are capable of the thiamine transport.[19] In some tissues, thiamine uptake and secretion appears to be mediated by a soluble thiamine transporter that is dependent on Na+ and a transcellular proton gradient.[12]

Tissue distribution

Human storage of thiamine is about 25 to 30 mg, with the greatest concentrations in skeletal muscle, heart, brain, liver, and kidneys. ThMP and free (unphosphorylated) thiamine is present in plasma, milk, cerebrospinal fluid, and, it is presumed, all extracellular fluid. Unlike the highly phosphorylated forms of thiamine, ThMP and free thiamine are capable of crossing cell membranes. Calcium and magnesium have been shown to affect the distribution of thiamine in the body and magnesium deficiency has been shown to aggravate thiamine deficiency.[19] Thiamine contents in human tissues are less than those of other species.[12][42]


Thiamine and its acid metabolites (2-methyl-4-amino-5-pyrimidine carboxylic acid, 4-methyl-thiazole-5-acetic acid, and thiamine acetic acid) are excreted principally in the urine.[22]


Its phosphate derivatives are involved in many cellular processes. The best-characterized form is thiamine pyrophosphate (TPP), a coenzyme in the catabolism of sugars and amino acids. In yeast, TPP is also required in the first step of alcoholic fermentation. All organisms use thiamine, but it is made only in bacteria, fungi, and plants. Animals must obtain it from their diet, and thus, for humans, it is an essential nutrient. Insufficient intake in birds produces a characteristic polyneuritis.

Thiamine is usually considered as the transport form of the vitamin. Five natural thiamine phosphate derivatives are known: thiamine monophosphate (ThMP), thiamine diphosphate (ThDP), also sometimes called thiamine pyrophosphate (TPP), thiamine triphosphate (ThTP), the most recently discovered adenosine thiamine triphosphate (AThTP), and adenosine thiamine diphosphate (AThDP). While the coenzyme role of thiamine diphosphate is well-known and extensively characterized, the non-coenzyme action of thiamine and derivatives may be realized through binding to a number of recently identified proteins which do not use the catalytic action of thiamine diphosphate.[43]

Thiamine diphosphate

No physiological role is known for thiamine monophosphate (ThMP); however, the diphosphate is physiologically relevant. The synthesis of thiamine diphosphate (ThDP), also known as thiamine pyrophosphate (TPP) or cocarboxylase, is catalyzed by an enzyme called thiamine diphosphokinase according to the reaction thiamine + ATP → ThDP + AMP (EC ThDP is a coenzyme for several enzymes that catalyze the transfer of two-carbon units and in particular the dehydrogenation (decarboxylation and subsequent conjugation with coenzyme A) of 2-oxoacids (alpha-keto acids). Examples include:

The enzymes transketolasepyruvate dehydrogenase (PDH), and 2-oxoglutarate dehydrogenase (OGDH) are all important in carbohydrate metabolism. The cytosolic enzyme transketolase is a key player in the pentose phosphate pathway, a major route for the biosynthesis of the pentose sugars deoxyribose and ribose. The mitochondrial PDH and OGDH are part of biochemical pathways that result in the generation of adenosine triphosphate (ATP), which is a major form of energy for the cell. PDH links glycolysis to the citric acid cycle, while the reaction catalyzed by OGDH is a rate-limiting step in the citric acid cycle. In the nervous system, PDH is also involved in the production of acetylcholine, a neurotransmitter, and for myelin synthesis.[44]

Thiamine triphosphate

Thiamine triphosphate (ThTP) was long considered a specific neuroactive form of thiamine, playing a role in chloride channels in the neurons of mammals and other animals, although this is not completely understood.[19] However, recently it was shown that ThTP exists in bacteriafungiplants and animals suggesting a much more general cellular role.[45] In particular in E. coli, it seems to play a role in response to amino acid starvation.[46]

Adenosine thiamine triphosphate

Adenosine thiamine triphosphate (AThTP) or thiaminylated adenosine triphosphate has recently been discovered in Escherichia coli, where it accumulates as a result of carbon starvation.[47] In E. coli, AThTP may account for up to 20% of total thiamine. It also exists in lesser amounts in yeast, roots of higher plants and animal tissue.[48]

Adenosine thiamine diphosphate

Adenosine thiamine diphosphate (AThDP) or thiaminylated adenosine diphosphate exists in small amounts in vertebrate liver, but its role remains unknown.[48]


Further information: Vitamin § History

Thiamine was the first of the water-soluble vitamins to be described,[11] leading to the discovery of more essential nutrients and to the notion of vitamin.

In 1884, Takaki Kanehiro (1849–1920), a surgeon general in the Japanese navy, rejected the previous germ theory for beriberi and hypothesized that the disease was due to insufficiencies in the diet instead.[49] Switching diets on a navy ship, he discovered that replacing a diet of white rice only with one also containing barley, meat, milk, bread, and vegetables, nearly eliminated beriberi on a nine-month sea voyage. However, Takaki had added many foods to the successful diet and he incorrectly attributed the benefit to increased protein intake, as vitamins were unknown substances at the time. The Navy was not convinced of the need for so expensive a program of dietary improvement, and many men continued to die of beriberi, even during the Russo-Japanese war of 1904–5. Not until 1905, after the anti-beriberi factor had been discovered in rice bran (removed by polishing into white rice) and in barley bran, was Takaki’s experiment rewarded by making him a baron in the Japanese peerage system, after which he was affectionately called “Barley Baron”.

The specific connection to grain was made in 1897 by Christiaan Eijkman (1858–1930), a military doctor in the Dutch Indies, who discovered that fowl fed on a diet of cooked, polished rice developed paralysis, which could be reversed by discontinuing rice polishing.[50] He attributed beriberi to the high levels of starch in rice being toxic. He believed that the toxicity was countered in a compound present in the rice polishings.[51] An associate, Gerrit Grijns (1865–1944), correctly interpreted the connection between excessive consumption of polished rice and beriberi in 1901: He concluded that rice contains an essential nutrient in the outer layers of the grain that is removed by polishing.[52] Eijkman was eventually awarded the Nobel Prize in Physiology and Medicine in 1929, because his observations led to the discovery of vitamins.

In 1910, a Japanese agricultural chemist of Tokyo Imperial UniversityUmetaro Suzuki (1874-1943), first isolated a water-soluble thiamine compound from rice bran and named it as aberic acid (He renamed it as Orizanin later). He described the compound is not only anti beri-beri factor but also essential nutrition to human in the paper, however, this finding failed to gain publicity outside of Japan, because a claim that the compound is a new finding was omitted in translation from Japanese to German.[53] In 1911 a Polish biochemist Casimir Funk isolated the antineuritic substance from rice bran (the modern thiamine) that he called a “vitamine” (on account of its containing an amino group).[54][55] However, Funk did not completely characterize its chemical structure. Dutch chemists, Barend Coenraad Petrus Jansen (1884–1962) and his closest collaborator Willem Frederik Donath (1889–1957), went on to isolate and crystallize the active agent in 1926,[56] whose structure was determined by Robert Runnels Williams (1886–1965), a US chemist, in 1934. Thiamine was named by the Williams team as “thio” or “sulfur-containing vitamin”, with the term “vitamin” coming indirectly, by way of Funk, from the amine group of thiamine itself (by this time in 1936, vitamins were known to not always be amines, for example, vitamin C). Thiamine was synthesized in 1936 by the Williams group.[57]

Thiamine was first named “aneurin” (for anti-neuritic vitamin).[58] Sir Rudolph Peters, in Oxford, introduced thiamine-deprived pigeons as a model for understanding how thiamine deficiency can lead to the pathological-physiological symptoms of beriberi. Indeed, feeding the pigeons upon polished rice leads to an easily recognizable behavior of head retraction, a condition called opisthotonos. If not treated, the animals died after a few days. Administration of thiamine at the stage of opisthotonos led to a complete cure within 30 minutes. As no morphological modifications were observed in the brain of the pigeons before and after treatment with thiamine, Peters introduced the concept of a biochemical lesion.[59]

When Lohman and Schuster (1937) showed that the diphosphorylated thiamine derivative (thiamine diphosphate, ThDP) was a cofactor required for the oxydative decarboxylation of pyruvate,[60] a reaction now known to be catalyzed by pyruvate dehydrogenase, the mechanism of action of thiamine in the cellular metabolism seemed to be elucidated. At present, this view seems to be oversimplified: pyruvate dehydrogenase is only one of several enzymes requiring thiamine diphosphate as a cofactor; moreover, other thiamine phosphate derivatives have been discovered since then, and they may also contribute to the symptoms observed during thiamine deficiency. Lastly, the mechanism by which the thiamine moiety of ThDP exerts its coenzyme function by proton substitution on position 2 of the thiazole ring was elucidated by Ronald Breslow in 1958.[61]

See also


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  53. ^ Suzuki U, Shimamura T (1911). “Active constituent of rice grits preventing bird polyneuritis”Tokyo Kagaku Kaishi32: 4–7, 144–146, 335–358. doi:10.1246/nikkashi1880.32.4.
  54. ^ Funk, Casimir (1911). “On the chemical nature of the substance which cures polyneuritis in birds induced by a diet of polished rice”The Journal of Physiology43 (5): 395–400. doi:10.1113/jphysiol.1911.sp001481PMC 1512869PMID 16993097.
  55. ^ Funk, Casimir (1912). “The etiology of the deficiency diseases. Beri-beri, polyneuritis in birds, epidemic dropsy, scurvy, experimental scurvy in animals, infantile scurvy, ship beri-beri, pellagra”Journal of State Medicine20: 341–368. The word “vitamine” is coined on p. 342: “It is now known that all these diseases, with the exception of pellagra, can be prevented and cured by the addition of certain preventative substances; the deficient substances, which are of the nature of organic bases, we will call “vitamines”; and we will speak of a beri-beri or scurvy vitamine, which means a substance preventing the special disease.”
  56. ^ Jansen BC, Donath WF (1926). “On the isolation of antiberiberi vitamin”. Proc. Kon. Ned. Akad. Wet29: 1390–1400.
  57. ^ Williams RR, Cline JK (1936). “Synthesis of vitamin B1“. J. Am. Chem. Soc58 (8): 1504–1505. doi:10.1021/ja01299a505.
  58. ^ Carpenter KJ (2000). “Beriberi, white rice, and vitamin B: a disease, a cause, and a cure”. Berkeley, CA: University of California Press.
  59. ^ Peters RA (1936). “The biochemical lesion in vitamin B1deficiency. Application of modern biochemical analysis in its diagnosis”. Lancet230 (5882): 1161–1164. doi:10.1016/S0140-6736(01)28025-8.
  60. ^ Lohmann K, Schuster P (1937). “Untersuchungen über die Cocarboxylase”. Biochem. Z294: 188–214.
  61. ^ Breslow R (1958). “On the mechanism of thiamine action. IV.1 Evidence from studies on model systems”. J Am Chem Soc80(14): 3719–3726. doi:10.1021/ja01547a064.

External links

  • “Thiamine”Drug Information Portal. U.S. National Library of Medicine.
Skeletal formula and ball-and-stick model of the cation in thiamine
Clinical data
Pronunciation/ˈθaɪ.əmɪn/ THY-ə-min
Other namesVitamin B1, aneurine, thiamin
License dataUS DailyMedThiamineUS FDAThiamine
Routes of
by mouth, IV, IM[1]
Drug classvitamin
ATC codeA11DA01 (WHO)
Legal status
Legal statusUS: OTC
Pharmacokinetic data
Bioavailability3.7% to 5.3%[medical citation needed]
Elimination half-life1.8d[2][better source needed]
showIUPAC name
CAS Number59-43-8  59-43-8 HCl: 67-03-8  
PubChem CID1130
UNIIX66NSO3N35HCl: M572600E5P 
CompTox Dashboard (EPA)DTXSID50220251 
Chemical and physical data
Molar mass265.35 g·mol−1
3D model (JSmol)Interactive image


  • Wikipedia: BeriberiChristiaan EijkmanAdolphe_VordermanCasimir_FunkRice PolishingWhite riceThiamineThiamine_pyrophosphateCitric Acid Cycle
  • A. Bay, “Beriberi in Modern Japan: The Making of a National Disease”, University of Rochester Press (2012).
  • K.J. Carpenter. Beriberi, White Rice and Vitamin B. University of California Press, 2000
  • M.C. Latham, . “Chapter 16. Beriberi and thiamine deficiency” in Human nutrition in the developing world29 [Rome, Food and Agriculture Organization of the United Nations, 1997].
  • D.-T. Nguyen-Khoa, Beriberi (Thiamine Deficiency) Treatment & Management
  • M. Golden, Mike . “Diagnosing Beriberi in Emergency Situations”. Field Exchange 1 (1997) 18.
  • Y. Itokawa, . “Kanehiro Takaki (1849–1920): A Biographical Sketch”. J. Nutrit106 (1976) 581–8.
  • R. Breslow. “On the mechanism of thiamine action. IV.1 Evidence from studies on model systems”. J. Am. Chem. Soc. 80 (1958) 3719–3726.
  • R.R. Williams, J.K. Cline,. “Synthesis of vitamin B1“. J. Am. Chem. Soc. 58 (1936) 1504–1505.
  • T.P. Begley, A.Chatterjee, J.W. Hanes, A. Hazra, S.E. Ealick,. “Cofactor biosynthesis—still yielding fascinating new biological chemistry”. Curr. Opin. in Chem. Biol. 12 (2008) 118–125.
  • L. Bettendorff, F. Mastrogiacomo, S.J. Kish, T. Grisar, “Thiamine, thiamine phosphates and their metabolizing enzymes in human brain”. J. Neurochem66 (1996) 250–258.
  • B.C.P. Jansen, W.F. Donath, “On the isolation of antiberiberi vitamin”. Proc. Kon. Ned. Akad. Wet29 (1926) 1390–1400.
  • C. Nordqvist, “What is Thiamin, or Vitamin B1?“, Medical News Today, (2016)
  • Thiamin, NIH Fact Sheet for Health Professionals.
  • Thiamine, Oregon State University

//////////THIAMINE, aneurin hydrochloride, vitamin b1



A vitamin (US /ˈvtəmɪn/ or UK /ˈvɪtəmɪn/) is an organic compound required by an organism as a vital nutrient in limited amounts. An organic chemical compound (or related set of compounds) is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on the circumstances and on the particular organism. For example, ascorbic acid (vitamin C) is a vitamin for humans, but not for most other animals, and biotin (vitamin H) and vitamin D are required in the human diet only in certain circumstances.






What it does:

  • helps convert the food we eat to the energy we need

Foods that have thiamin:

  • spinach, tomato juice, watermelon, sunflower seeds, ham

Deficiency problems:

  • weakness, tingling in feet and hands, poor coordination

Riboflavin – named for its yellow color (flavus means yellow in Latin)

What it does:

  • helps convert the food we eat to the energy we need

Foods that have riboflavin:

  • milk, cheese, liver, broccoli, asparagus, spinach

Deficiency problems:

  • eye disorders, cracks at corners of mouth, swollen tongue


What it does:

  • helps our body use the fat and sugar we eat for energy
  • helps keep our skin healthy

Foods that have niacin:

  • mushrooms, tuna, green beans, broccoli, spinach, breakfast cereals

Deficiency problems:

  • diarrhea, skin problems, mental disorientation

Vitamin B6

What it does:

  • helps make red blood cells
  • helps our body use the fat and protein we eat for energy

Foods that have vitamin B6:

  • spinach, broccoli, tomato juice, banana, watermelon, chicken breast

Deficiency problems:

  • headache, convulsions, vomiting, flaky skin, sore tongue


What it does:

  • helps to make new cells
  • helps prevent heart disease

Foods that have folate:

  • asparagus, broccoli, corn flakes, green beans, tomato juice, beans

Deficiency problems:

  • diarrhea, mental disorders, poor growth

Vitamin B12

What it does:

  • helps to make new cells

Foods that have vitamin B12:

  • meat, fish, poultry, milk, cheese, eggs

Deficiency problems:

  • anemia, poor nerve function

Vitamin C– almost all animals make vitamin C in their bodies (only humans, guinea pigs, some bats, and some fish don’t)vitamin c

What it does:

  • protects cells from damage
  • helps keep bones and skin healthy
  • may help prevent cancer and heart disease

Foods that have vitamin C:

  • oranges, strawberries, peppers, kiwi, brussel sprouts, broccoli, spinach

Deficiency problems:

  • bleeding gums, tiredness, weakness, sore muscle









Vitamin A – discovered in 1913

What it does:

  • helps with eyesight
  • keeps skin healthy
  • helps with growth of body organs (like bones)

Foods that have vitamin A:

  • liver, fish, milk, butter, eggs, carrots

Deficiency problems:

  • night blindness, poor growth, dry skin
vitamin a

Vitamin D – made in the skin by the sun

What it does:

  • helps bones grow strong

Foods that have vitamin D:

  • egg yolks, liver, butter, milk

Deficiency problems:

  • rickets (deformed bones), weak bones
vitamin d

Vitamin E – called the antiaging vitamin

What it does:

  • protects lungs against pollution damage
  • helps keep heart healthy
  • may help protect against cancer

Foods that have vitamin E:

  • sweet potatoes, peanut butter, sunflower seeds, spinach, nuts

Deficiency problems:

  • nerve destruction, red blood cell destruction
vitamin e

Vitamin K – made by bacteria in our intestines

What it does:

  • helps make blood clot
  • helps keep bones healthy

Foods that have vitamin K:

  • liver, cabbage, lettuce, spinach, milk, meat, eggs

Deficiency problems:

  • hemorrhage
vitamin k


By convention, the term vitamin includes neither other essential nutrients, such as dietary mineralsessential fatty acids, or essential amino acids (which are needed in larger amounts than vitamins) nor the large number of other nutrients that promote health but are otherwise required less often. Thirteen vitamins are universally recognized at present.

Vitamins are classified by their biological and chemical activity, not their structure. Thus, each “vitamin” refers to a number of vitamer compounds that all show the biological activity associated with a particular vitamin. Such a set of chemicals is grouped under an alphabetized vitamin “generic descriptor” title, such as “vitamin A“, which includes the compounds retinalretinol, and four known carotenoids. Vitamers by definition are convertible to the active form of the vitamin in the body, and are sometimes inter-convertible to one another, as well.

itamins have diverse biochemical functions. Some, such as vitamin D, have hormone-like functions as regulators of mineral metabolism, or regulators of cell and tissue growth and differentiation (such as some forms of vitamin A). Others function as antioxidants (e.g., vitamin E and sometimesvitamin C). The largest number of vitamins, the B complex vitamins, function as precursors for enzyme cofactors, that help enzymes in their work as catalysts in metabolism. In this role, vitamins may be tightly bound to enzymes as part of prosthetic groups: For example, biotin is part of enzymes involved in making fatty acids. They may also be less tightly bound to enzyme catalysts as coenzymes, detachable molecules that function to carry chemical groups or electrons between molecules. For example, folic acid may carry methylformyl, and methylene groups in the cell. Although these roles in assisting enzyme-substrate reactions are vitamins’ best-known function, the other vitamin functions are equally important.


Until the mid-1930s, when the first commercial yeast-extract vitamin B complex and semi-synthetic vitamin C supplement tablets were sold, vitamins were obtained solely through food intake, and changes in diet (which, for example, could occur during a particular growing season) usually greatly altered the types and amounts of vitamins ingested. However, vitamins have been produced as commodity chemicals and made widely available as inexpensive semisynthetic and synthetic-source multivitamin dietary and food supplements and additives, since the middle of the 20th century.,,,,,,,


List of vitamins

Each vitamin is typically used in multiple reactions, and, therefore, most have multiple functions.

Vitamin generic

descriptor name

Vitamerchemical name(s) (list not complete) Solubility Recommended dietary allowances

(male, age 19–70)[6]

Deficiency disease Upper Intake Level


Overdose disease Food sources
Vitamin A Retinolretinal, and

four carotenoids

including beta carotene

Fat 900 µg Night-blindness,Hyperkeratosis, andKeratomalacia[7] 3,000 µg Hypervitaminosis A Orange, ripe yellow fruits, leafy vegetables, carrots, pumpkin, squash, spinach, liver, soy milk, milk
Vitamin B1 Thiamine Water 1.2 mg BeriberiWernicke-Korsakoff syndrome N/D[8] Drowsiness or muscle relaxation with large doses.[9] Pork, oatmeal, brown rice, vegetables, potatoes, liver, eggs
Vitamin B2 Riboflavin Water 1.3 mg Ariboflavinosis N/D Dairy products, bananas, popcorn, green beans, asparagus
Vitamin B3 Niacinniacinamide Water 16.0 mg Pellagra 35.0 mg Liver damage (doses > 2g/day)[10] and other problems Meat, fish, eggs, many vegetables, mushrooms, tree nuts
Vitamin B5 Pantothenic acid Water 5.0 mg[11] Paresthesia N/D Diarrhea; possibly nausea and heartburn.[12] Meat, broccoli, avocados
Vitamin B6 Pyridoxine,pyridoxamine,pyridoxal Water 1.3–1.7 mg Anemia[13] peripheral neuropathy. 100 mg Impairment ofproprioception, nerve damage (doses > 100 mg/day) Meat, vegetables, tree nuts, bananas
Vitamin B7 Biotin Water 30.0 µg Dermatitisenteritis N/D Raw egg yolk, liver, peanuts, certain vegetables
Vitamin B9 Folic acidfolinic acid Water 400 µg Megaloblastic anemiaand Deficiency during pregnancy is associated with birth defects, such as neural tube defects 1,000 µg May mask symptoms of vitamin B12 deficiency;other effects. Leafy vegetables, pasta, bread, cereal, liver
Vitamin B12 Cyanocobalamin,hydroxycobalamin,methylcobalamin Water 2.4 µg Megaloblastic anemia[14] N/D Acne-like rash [causality is not conclusively established]. Meat and other animal products
Vitamin C Ascorbic acid Water 90.0 mg Scurvy 2,000 mg Vitamin C megadosage Many fruits and vegetables, liver
Vitamin D Cholecalciferol Fat 10 µg[15] Rickets andOsteomalacia 50 µg Hypervitaminosis D Fish, eggs, liver, mushrooms
Vitamin E Tocopherols,tocotrienols Fat 15.0 mg Deficiency is very rare; mild hemolytic anemiain newborn infants.[16] 1,000 mg Increased congestive heart failure seen in one large randomized study.[17] Many fruits and vegetables, nuts and seeds
Vitamin K phylloquinone,menaquinones Fat 120 µg Bleeding diathesis N/D Increases coagulation in patients taking warfarin.[18] Leafy green vegetables such as spinach, egg yolks, liver



File:L-Ascorbic acid.svg

Vitamin C


(R)-3,4-dihydroxy-5-((S)- 1,2-dihydroxyethyl)furan-2(5H)-one

James Lind, a British Royal Navy surgeon who, in 1747, identified that a quality in fruit prevented the disease of scurvy in what was the first recorded controlled experiment.

The need to include fresh plant food or raw animal flesh in the diet to prevent disease was known from ancient times. Native people living in marginal areas incorporated this into their medicinal lore. For example, spruce needles were used in temperate zones in infusions, or the leaves from species of drought-resistant trees in desert areas. In 1536, the French explorers Jacques Cartier and Daniel Knezevic, exploring the St. Lawrence River, used the local natives’ knowledge to save his men who were dying of scurvy. He boiled the needles of the arbor vitae tree to make a tea that was later shown to contain 50 mg of vitamin C per 100 grams

Citrus fruits were one of the first sources of vitamin C available to ships’ surgeons.

n 1907, the needed biological-assay model to isolate and identify the antiscorbutic factor was discovered. Axel Holst and Theodor Frølich, two Norwegian physicians studying shipboard beriberi in the Norwegian fishing fleet, wanted a small test mammal to substitute for the pigeons then used in beriberi research. They fed guinea pigs their test diet of grains and flour, which had earlier produced beriberi in their pigeons, and were surprised when classic scurvy resulted instead. This was a serendipitous choice of model. Until that time, scurvy had not been observed in any organism apart from humans, and had been considered an exclusively human disease. (Pigeons, as seed-eating birds, were also later found to make their own vitamin C.) Holst and Frølich found they could cure the disease in guinea pigs with the addition of various fresh foods and extracts. This discovery of a clean animal experimental model for scurvy, made even before the essential idea of vitamins in foods had even been put forward, has been called the single most important piece of vitamin C research

Vitamin C

 or L-ascorbic acid, or simply ascorbate (the anion of ascorbic acid), is anessential nutrient for humans and certain other animal species. Vitamin C refers to a number of vitamers that have vitamin C activity in animals, including ascorbic acid and its salts, and some oxidized forms of the molecule like dehydroascorbic acid. Ascorbate and ascorbic acid are both naturally present in the body when either of these is introduced into cells, since the forms interconvert according to pH.

Vitamin C is a cofactor in at least eight enzymatic reactions including several collagensynthesis reactions that, when dysfunctional, cause the most severe symptoms ofscurvy. In animals, these reactions are especially important in wound-healing and in preventing bleeding from capillaries. Ascorbate may also act as an antioxidant againstoxidative stress.However, the fact that the enantiomer D-ascorbate (not found in nature) has identical antioxidant activity to L-ascorbate, yet far less vitamin activity,underscores the fact that most of the function of L-ascorbate as a vitamin relies not on its antioxidant properties, but upon enzymic reactions that are stereospecific. “Ascorbate” without the letter for the enantiomeric form is always presumed to be the chemical L-ascorbate.

Ascorbate (the anion of ascorbic acid) is required for a range of essential metabolic reactions in all animals and plants. It is made internally by almost all organisms; the main exceptions are bats, guinea pigs, capybaras, and the Anthropoidea (i.e., Haplorrhini, one of the two major primate suborders, consisting of tarsiers, monkeys, humans and otherapes). Ascorbate is also not synthesized by some species of birds and fish. All species that do not synthesize ascorbate require it in the diet. Deficiency in this vitamin causes the disease scurvy in humans.

Ascorbic acid is also widely used as a food additive, to prevent oxidation.

ascorbic acid
(reduced form)
dehydroascorbic acid
(oxidized form)

The name vitamin C always refers to the L-enantiomer of ascorbic acid and its oxidized forms. The opposite D-enantiomer called D-ascorbate has equal antioxidant power, but is not found in nature, and has no physiological significance. When D-ascorbate is synthesized and given to animals that require vitamin C in the diet, it has been found to have far less vitamin activity than the L-enantiomer.Therefore, unless written otherwise, “ascorbate” and “ascorbic acid” refer in the nutritional literature to L-ascorbate and L-ascorbic acid respectively. This notation will be followed in this article. Similarly, their oxidized derivatives (dehydroascorbate, etc., see below) are all L-enantiomers, and also need not be written with full sterochemical notation here.

Ascorbic acid is a weak sugar acid structurally related to glucose. In biological systems, ascorbic acid can be found only at low pH, but in neutral solutions above pH 5 is predominantly found in the ionizedform, ascorbate. All of these molecules have vitamin C activity, therefore, and are used synonymously with vitamin C, unless otherwise specified

Rose hips are a particularly rich source of vitamin C

Goats, like almost all animals, make their own vitamin C. An adult goat, weighing approx. 70 kg, will manufacture more than 13,000 mg of vitamin C per day in normal health, and levels manyfold higher when faced with stress.\


Terminalia ferdinandiana, also called the gubingebillygoat plumKakadu plum ormurunga is a flowering plant in the family Combretaceae, native to Australia, widespread throughout the tropical woodlands from northwestern Australia to eastern Arnhem Land.

Its vitamin C concentration may be as high as 1000–5300 mg/100g  (compared with 50 mg/100g for oranges), possibly the highest known of any fruit.

Phyllanthus emblica (syn. Emblica officinalis), the Indian gooseberry, or aamla from Sanskrit amalika, is a deciduous tree of the family Phyllanthaceae. It is known for its ediblefruit of the same name.




Ascorbic Acid

Structure of ascorbic acid

Ascorbic acid is more commonly known as vitamin C. Ascorbic acid is derived from glucose via the uronic acid pathway. The enzyme L-gulonolactone oxidase responsible for the conversion of gulonolactone to ascorbic acid is absent in primates making ascorbic acid required in the diet.

The active form of vitamin C is ascorbic acid itself. The main function of ascorbate is as a reducing agent in a number of different reactions. Ascorbate is the cofactor for Cu+–dependent monooxygenases and Fe2+–dependent dioxygenases. Ascorbate has the potential to reduce cytochromes a and c of the respiratory chain as well as molecular oxygen. The most important reaction requiring ascorbate as a cofactor is the hydroxylation of proline residues in collagen. Vitamin C is, therefore, required for the maintenance of normal connective tissue as well as for wound healing since synthesis of connective tissue is the first event in wound tissue remodeling. Vitamin C also is necessary for bone remodeling due to the presence of collagen in the organic matrix of bones.

Ascorbic acid also serves as a reducing agent and an antioxidant. When functioning as an antioxidant ascorbic acid itself becomes oxidized to semidehydroascorbate and then dehydroascorbate. Semidehydroascorbate is reconverted to ascorbate in the cytosol by cytochrome b5 reductase and thioredoxin reductase in reactions involving NADH and NADPH, respectively. Dehydroascorbate, the fully oxidized form of vitamin C, is reduced spontaneously by glutathione, as well as enzymatically in reactions using glutathione or NADPH.

Several other metabolic reactions require vitamin C as a cofactor. These include the catabolism of tyrosine and the synthesis of epinephrine from tyrosine and the synthesis of the bile acids. It is also believed that vitamin C is involved in the process of steroidogenesis since the adrenal cortex contains high levels of vitamin C which are depleted upon adrenocorticotropic hormone (ACTH) stimulation of the gland.

Deficiency in vitamin C leads to the disease scurvy due to the role of the vitamin in the post-translational modification of collagens. Scurvy is characterized by easily bruised skin, muscle fatigue, soft swollen gums, decreased wound healing and hemorrhaging, osteoporosis, and anemia. Vitamin C is readily absorbed and so the primary cause of vitamin C deficiency is poor diet and/or an increased requirement. The primary physiological state leading to an increased requirement for vitamin C is severe stress (or trauma). This is due to a rapid depletion in the adrenal stores of the vitamin. The reason for the decrease in adrenal vitamin C levels is unclear but may be due either to redistribution of the vitamin to areas that need it or an overall increased utilization.

Inefficient intake of vitamin C has also been associated with a number of conditions, such as high blood pressure, gallbladder disease, stroke, some cancers, and atherosclerosis (plaque in blood vessels that can lead to heart attack and stroke). Sufficient vitamin C in the diet may help reduce the risk of developing some of these conditions, however, the evidence that taking vitamin C supplements will help or prevent any of these conditions is still lacking.

The amount of vitamin C that is recommended to consume each day (the RDA) depends upon the age and sex of the individual. Infants less than 1 year old should get 50 milligrams (mg) per day. children 1–3 years old need 15mg, 4–8 years old need 25mg, and 9–13 years old need 45mg. Adolescent girls should get 65mg per day and adolescent boys should get 75mg per day. Adult males need 90mg per day and adult women should get 75mg per day. Women who are breastfeeding should increase their intake to at least 120mg per day. Individuals who smoke should increase their daily intake by at least 35mg since smoking depletes vitamin C levels. The recommended daily intake of vitamin C to prevent conditions such as the cardiovascular disorders indicated above is reported to be between 500mg and 1000mg.

Excellent sources of vitamin C are fruits and vegetables such as oranges, watermelon, papaya, grapefruit, cantaloupe, strawberries, raspberries, blueberries, cranberries, pineapple, kiwi, mango, green peppers, broccoli, turnip greens, spinach, red and green peppers, canned and fresh tomatoes, potatoes, Brussels sprouts, cauliflower, and cabbage. Citrus juices or juices fortified with vitamin C are also excellent sources of the vitamin.

Vitamin C is sensitive to light, air, and heat, so the most vitamin C is available in fruits and vegetables that are eaten raw or lightly cooked. Natural or synthetic vitamin C can be found in a variety of forms. Tablets, capsules, and chewables are probably the most popular forms, but vitamin C also comes in powdered crystalline, effervescent, and liquid forms. An esterified form of vitamin C is also available, which may be easier on the stomach for those who are prone to heartburn. The best way to take vitamin C supplements is 2–3 times per day, with meals, depending on the dosage.

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