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The α-tocopherol form of vitamin E

Vitamin E refers to a group of eight fat-soluble compounds that include both tocopherolsand tocotrienols.[1] There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet.[2] γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings.[3][4] In the North American diet, α-Tocopherol, the most biologically active form of vitamin E, is the second most common form of vitamin E. This variant of vitamin E can be found most abundantly in wheat germ oil, sunflower, and safflower oils.[4][5] It is a fat-soluble antioxidant that stops the production of reactive oxygen species formed when fat undergoes oxidation.[6][7][8]

  • Synthesis of Vitamin E

Vitamin E (CAS NO.: 59-02-9), with other names as 2(R),5,7,8-Tetramethyl-2-[4(R),8(R),12-trimethyltridecyl]-3,4-dihydro-2H-1-benzopyran-6-ol, could be produced through the following synthetic routes.Dictionary,

 Synthesis of Vitamin E
           Synthesis of Vitamin E
The chlorination of myrcene (I) with Cl2 in refluxing pentane gives the choromyrcene (II), and the hydrochlorination of (I) catalyzed by CuCl yields a mixture of geranyl/neryl chloride (III). The reductive coupling of (II) and (III) by means of Mg and CuCl affords beta-springene (IV), which is condensed with 2,3,6-trimethylhydroquinone (V) by means of cyclooctadienyl rhodium chloride dimer [RhCl(COD)]2 and K2CO3 in refluxing toluene to provide the adduct (VI). The cyclization of (VI) by means of MeAlCl2 of Ts-OH in refluxing hexane furnishes the tocotrienol (VII), which is finally hydrogenated with H2 over Pd/C in ethanol to give the target (rac)-vitamin E.

 LinksReferences

  1. Brigelius-Flohe, B; Traber (1999). “Vitamin E: function and metabolism”. FASEB 13: 1145–1155.
  2. Traber, MG (1998). “The biological activity of vitamin E”. The Linus Pauling Institute. Retrieved 6 March 2011.
  3. Bieri, JG; Evarts (1974). “γ-Tocopherol: metabolism, biological activity and significance in human vitamin E nutrition”. American Journal of Clinical Nutrition 27 (9): 980–986. PMID 4472121.
  4. Brigelius-Flohé R, Traber MG (1 July 1999). “Vitamin E: function and metabolism”. FASEB J. 13 (10): 1145–55. PMID 10385606.
  5. Reboul E, Richelle M, Perrot E, Desmoulins-Malezet C, Pirisi V, Borel P (15 November 2006). “Bioaccessibility of carotenoids and vitamin E from their main dietary sources”. Journal of Agricultural and Food Chemistry 54 (23): 8749–8755. doi:10.1021/jf061818s.PMID 17090117.
  6. National Institute of Health (4 May 2009). “Vitamin E fact sheet”.
  7. Herrera; Barbas, C (2001). “Vitamin E: action, metabolism and perspectives”. Journal of Physiology and Biochemistry 57 (2): 43–56.doi:10.1007/BF03179812PMID 11579997.
  8. Packer L, Weber SU, Rimbach G (2001). “Molecular aspects of α-tocotrienol antioxidant action and cell signalling”Journal of Nutrition 131 (2): 369S–73S. PMID 11160563.

DR ANTHONY MELVIN CRASTO Ph.D

ANTHONY MELVIN CRASTO

amcrasto@gmail.com

MOBILE-+91 9323115463
GLENMARK SCIENTIST , NAVIMUMBAI, INDIA

DR ANTHONY CRASTO, PhD, ICT Organic chemistry, Currently working with GLENMARK GENERICS LTD research centre as Principal Scientist, process research (bulk actives) at Mahape, Navi Mumbai, India, helping millions, million hits on google on all organic chemistry websites, Hands on experience in developing novel routes for drug molecules and implementation on commercial scale. several international patents published.pushing boundaries, one lakh connections on all networking sites

Jan. 18, 2013
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Donepezil, marketed under the trade name Aricept by its developer Eisai and partner Pfizer, is a centrally acting reversible acetylcholinesterase inhibitor.[1]Its main therapeutic use is in the palliative treatment of mild to moderateAlzheimer’s disease.[2] Common side effects include gastrointestinal upset. It has an oral bioavailability of 100% and easily crosses the blood–brain barrier. Because it has a half-life of about 70 hours, it can be taken once a day.

(RS)-2-[(1-benzyl-4-piperidyl)methyl]- 5,6-dimethoxy-2,3-dihydroinden-1-one

Donepezil

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Synthesis

The condensation of 5,6-dimethoxy-1-indanone (I) with 1-benzylpiperidine-4-carboxaldehyde (II) by means of butyl lithium and diisopropylamine in THF gives 1-benzyl-4-(5,6-dimethoxy-1-oxoindan-2-ylidenemethyl)piperidine (III), which is reduced with H2 over Pd/C in THF and treated with HCl in dichloromethane – ethyl acetate (1,2).

Manufacturer Eisai Co., Ltd. (Japan).

References

1. Sugimoto, H., Tsuchiya, Y., Higurashi, K. et al. (Eisai Co., Ltd.) Cyclic amine cpd., its use and pharmaceutical compsns. comprising it. AU 8818216, EP 296560, JP 89079151, US 4895841.

2. Iimura, Y., Mishima, M., Sugimoto, H. Synthesis of 1-benzyl-4-[(5,6-dimethoxy[2-14C]-1-indanon)-2-yl]methylpiperidine hydrochloride (E-2020-14C). J Label Compound Radiopharm 1989, 27(7): 835-9.

  1. 1        Birks J, Harvey RJ (2006). Birks, Jacqueline. ed. “Donepezil for dementia due to Alzheimer’s disease”. Cochrane Database Syst Rev (1): CD001190.doi:10.1002/14651858.CD001190.pub2PMID 16437430.
  2. 2       “aricept”The American Society of Health-System Pharmacists. Retrieved 3 April 2011.

OTHER1

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OTHER 2

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OTHER3

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OTHER4

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SPECTROSCOPY

MASS

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13C NMR

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DEPT 90 C13 NMR

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DEPT135

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IR

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1H NMR

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COSY 1H NMR

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HSQC NMR

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HMBC NMR

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DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai) , INDIA 25Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK GENERICS at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.Million hits on google NO ADVERTISEMENTS , ACADEMIC , NON COMMERCIAL SITE, world acclamation from industry, academia, drug authorities for websites, blogs and educational contribution,email or call now for sure success formula, amcrasto@gmail.com, 9323115463. you can swim to the shore even if you are drowned in a storm.

Jan. 18, 2013
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Sertraline hydrochloride (trade names Zoloft and Lustral, among others) is anantidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It was discovered byPfizer. Sertraline is primarily used to treat major depression in adult outpatients as well asobsessive–compulsivepanic, and social anxiety disorders in both adults and children

Sertraline

Schematic Representation for Synthesis of Sertraline

Conditions:-

i. Benzene, anhydrous aluminum chloride, dichloromethane,

ii. Diethyl succinate, potassium-t-butoxide, t-butyl alcohol, reflux, 16 h,

iii. 48% aqueous HBr, acetic acid, reflux, 36 h,

iv. Hydrogen gas (1 atm), 5% Pd/c catalyst, ethyl acetate, room temperature, 24 h,

v. a) Thionyl chloride, toluene, reflux, 75 min b) anhydrous aluminum chloride, carbon disulfide, room temperature, 16 h,

vi. Methylamine, tetrahydrofuran, titanium tetrachloride, room temperature, 17 h,

vii. a) Hydrogen gas (1 atm), 10% Pd/c catalyst, tetrahydrofuran, room temperature, 2 h b) Gaseous hydrogen chloride,

viii. Crystallization from methanol and ether,

ix) a) 20% sodium hydroxide, ethyl acetate b) D (-) Mandelic acid, ethanol, resolution

Sertraline

CAS No:- [79617-96-2]

IUPAC Name:- (1S,4S)-4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine

MW: 306.23

Drug information:- Sertraline is an anti-depressant drug.

DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai) , INDIA 25Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK GENERICS at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.Million hits on google NO ADVERTISEMENTS , ACADEMIC , NON COMMERCIAL SITE, world acclamation from industry, academia, drug authorities for websites, blogs and educational contribution,email or call now for sure success formula, amcrasto@gmail.com, 9323115463. you can swim to the shore even if you are drowned in a storm.

Jan. 18, 2013
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2-acetoxybenzoic acid

Aspirin (USAN), also known as acetylsalicylic acid is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatorymedication. Aspirin was first isolated by Felix Hoffmann, a chemist with the German company Bayer in 1897.[1][2]

Salicylic acid, the main metabolite of aspirin, is an integral part of human and animal metabolism. While in humans much of it is attributable to diet, a substantial part is synthesized endogenously.[3]

Aspirin also has an antiplatelet effect by inhibiting the production of thromboxane, which under normal circumstances binds platelet molecules together to create a patch over damaged walls of blood vessels. Because the platelet patch can become too large and also block blood flow, locally and downstream, aspirin is also used long-term, at low doses, to help prevent heart attacksstrokes, and blood clot formation in people at high risk of developing blood clots.[4] It has also been established that low doses of aspirin may be given immediately after a heart attack to reduce the risk of another heart attack or of the death of cardiac tissue.[5][6] Aspirin may be effective at preventing certain types of cancer, particularly colorectal cancer.[7][7][8][9]

The main undesirable side effects of aspirin taken by mouth are gastrointestinal ulcers, stomach bleeding, and tinnitus, especially in higher doses. In children and adolescents, aspirin is no longer indicated to control flu-like symptoms or the symptoms of chickenpoxor other viral illnesses, because of the risk of Reye’s syndrome.[10]

Advertisement for Aspirin,

Aspirin is part of a group of medications called nonsteroidal anti-inflammatory drugs(NSAIDs), but differs from most other NSAIDs in the mechanism of action. Though it, and others in its group called the salicylates, have similar effects (antipyretic, anti-inflammatory, analgesic) to the other NSAIDs and inhibit the same enzymecyclooxygenase, aspirin (but not the other salicylates) does so in an irreversible manner and, unlike others, affects more the COX-1 variant than the COX-2 variant of the enzyme.[11]

Today, aspirin is one of the most widely used medications in the world, with an estimated 40,000 tonnes of it being consumed each year.[12] In countries where Aspirin is a registered trademark owned by Bayer, the generic term is acetylsalicylic acid (ASA).[13]

1923 advertisement

Synthesis

The synthesis of aspirin is classified as an esterification reaction. Salicylic acid is treated with acetic anhydride, an acid derivative, causing a chemical reaction that turns salicylic acid’s hydroxyl group into an ester group (R-OH → R-OCOCH3). This process yields aspirin and acetic acid, which is considered a byproduct of this reaction. Small amounts of sulfuric acid (and occasionally phosphoric acid) are almost always used as a catalyst. This method is commonly employed in undergraduate teaching labs.[104]

Aspirin synthesis.png
Reaction Mechanism
Acetylation of salicylic acid, mechanism
  1. Sneader, W. (2000). “The discovery of aspirin: A reappraisal”BMJ (Clinical research ed.) 321 (7276): 1591–1594. doi:10.1136/bmj.321.7276.1591PMC 1119266.PMID 11124191edit
  2. Karsten Schrör (2009). Acetylsalicylic acidISBN 978-3-527-32109-4.
  3. Paterson, John R.; Baxter, Gwendoline; Dreyer, Jacob S.; Halket, John M.; Flynn, Robert; Lawrence, James R. (2008).“Salicylic Acid sans Aspirin in Animals and Man: Persistence in Fasting and Biosynthesis from Benzoic Acid”Journal of Agricultural and Food Chemistry 56 (24): 11648–11652.doi:10.1021/jf800974zPMC 2800778.PMID 19053387edit
  4. Lewis, H D; J W Davis, D G Archibald, W E Steinke, T C Smitherman, J E Doherty, H W Schnaper, M M LeWinter, E Linares, J M Pouget, S C Sabharwal, E Chesler, H DeMots (18 August 1983). “Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study”. The New England Journal of Medicine 309 (7): 396–403.doi:10.1056/NEJM198308183090703ISSN 00284793.PMID 6135989.
  5. Julian, D G; D A Chamberlain, S J Pocock (24 September 1996). “A comparison of aspirin and anticoagulation following thrombolysis for myocardial infarction (the AFTER study): a multicentre unblinded randomised clinical trial”BMJ (British Medical Journal) 313 (7070): 1429–1431.doi:10.1136/bmj.313.7070.1429PMC 2353012.PMID 8973228.
  6. Krumholz, Harlan M.; Martha J. Radford, Edward F. Ellerbeck, John Hennen, Thomas P. Meehan, Marcia Petrillo, Yun Wang, Timothy F. Kresowik, Stephen F. Jencks (1995). “Aspirin in the Treatment of Acute Myocardial Infarction in Elderly Medicare Beneficiaries : Patterns of Use and Outcomes”. Circulation 92(10): 2841–2847. PMID 7586250.
  7. Algra, Annemijn M; Rothwell, Peter M (2012). “Effects of regular aspirin on long-term cancer incidence and metastasis: A systematic comparison of evidence from observational studies versus randomised trials”The Lancet Oncology.doi:10.1016/S1470-2045(12)70112-2.
  8. Rothwell, Peter M; Price, Jacqueline F; Fowkes, F Gerald R; Zanchetti, Alberto; Roncaglioni, Maria Carla; Tognoni, Gianni; Lee, Robert; Belch, Jill FF et al. (2012). “Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: Analysis of the time course of risks and benefits in 51 randomised controlled trials”. The Lancetdoi:10.1016/S0140-6736(11)61720-0. Rothwell, Peter M; Wilson, Michelle; Price, Jacqueline F; Belch, Jill FF; Meade, Tom W; Mehta, Ziyah (2012). “Effect of daily aspirin on risk of cancer metastasis: A study of incident cancers during randomised controlled trials”. The Lancet.doi:10.1016/S0140-6736(12)60209-8.
  9. Macdonald S (2002). “Aspirin use to be banned in under 16 year olds”BMJ 325 (7371): 988.doi:10.1136/bmj.325.7371.988/cPMC 1169585.PMID 12411346.
  10. Burke, Anne; Smyth, Emer; FitzGerald, Garret A. (2006). “26: Analgesic Antipyretic and Antiinflammatory Agents”.Goodman and Gilman’s the pharmacological basis of therapeutics (11 ed.). New York: McGraw-Hill. pp. 671–716.ISBN 978-0-07-142280-2.
  11. Warner, T. D.; Warner TD, Mitchell JA (2002).“Cyclooxygenase-3 (COX-3): filling in the gaps toward a COX continuum?”Proc Natl Acad Sci USA 99 (21): 13371–3.doi:10.1073/pnas.222543099PMC 129677.PMID 12374850.
  12.  “The use of aspirin”. Wordconstructions.com. Retrieved 11 May 2011.

     

    1. DR ANTHONY MELVIN CRASTO Ph.DANTHONY MELVIN CRASTOamcrasto@gmail.com
      MOBILE-+91 9323115463
      GLENMARK SCIENTIST , NAVIMUMBAI, INDIA
    2. DR ANTHONY MELVIN CRASTO Ph.D , Born in Mumbai in 1964 and graduated from Mumbai University, Completed his  PhD from ICT ,1991,  Mumbai, India in Organic chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues,

      Currently he is working with GLENMARK- GENERICS LTD, Research centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India.

      Prior to joining Glenmark, he worked with major multinationals like Hoechst Marion Roussel, now Sanofi Aventis,  & Searle India ltd, now Rpg lifesciences, etc. He has worked in Basic research, Neutraceuticals, Natural products, Flavors, Fragrances, Pheromones, Vet Drugs, Drugs, formulation, GMP etc. He has total 25 yrs exp in this field, he is now helping millions, has million hits on google on all organic chemistry websites.

      His New Drug Approvals ,  Green Chemistry International,  Eurekamoments in Organic Chemistry ,  Organic Chemistry by Dr AnthonyWIX BLOG , are some most read chemistry blogs

      He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 25 year tenure, good knowledge of IPM, GMP, Regulatory aspects, he has  several international drug patents published worldwide .

      He has good proficiency in Technology Transfer, Spectroscopy , Stereochemistry , Synthesis, Reactions in Org Chem , Polymorphism,  Pharmaceuticals , Medicinal chemistry , Organic chemistry literature , Patent related site , Green chemistry , Reagents , R & D , Molecules , Heterocyclic chem , Sourcing   etc

      He suffered a paralytic stroke in dec 2006 and is bound to a wheelchair, this seems to have injected feul in him to help chemists around the world, he is more active than before and is pushing boundaries, he has one lakh connections on all networking sites, He makes himself available to all, contact him on  +91 9323115463, amcrasto@gmail.com

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1 Comment

  1. Hey would you mind sharing which blog platform you’re using? I’m
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    P.S My apologies for getting off-topic but I had to ask!

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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

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 GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 29 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 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 29 year tenure till date Aug 2016, Around 30 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 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 25 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 13 lakh plus views on New Drug Approvals Blog in 212 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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