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ORGANIC SPECTROSCOPY

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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 30 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, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, 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 30 year tenure till date Dec 2017, 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 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 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 19 lakh plus views on New Drug Approvals Blog in 216 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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Specific Stereoisomeric Conformations Determine the Drug Potency of Cladosporin Scaffold against Malarial Parasite


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Specific Stereoisomeric Conformations Determine the Drug Potency of Cladosporin Scaffold against Malarial Parasite

https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.8b00565

Pronay Das†ab, Palak Babbar†c, Nipun Malhotra†c, Manmohan Sharmac , Goraknath R. Jachakab , Rajesh G. Gonnadebd, Dhanasekaran Shanmugambe, Karl Harlosf , Manickam Yogavelc , Amit Sharmac *, and D. Srinivasa Reddyab* †All three have contributed equally to this work.
aOrganic Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India
b Academy of Scientific and Innovative Research (AcSIR), New Delhi 110025, India
cMolecular Medicine Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi 110067, India dCenter for Material Characterization, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India
e Biochemical Sciences Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India
fDivision of Structural Biology, Welcome Trust Centre for Human Genetics, The Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK
J. Med. Chem., Just Accepted Manuscript
DOI: 10.1021/acs.jmedchem.8b00565
Publication Date (Web): May 21, 2018
Copyright © 2018 American Chemical Society
The dependence of drug potency on diastereomeric configurations is a key facet. Using a novel general divergent synthetic route for a three-chiral centre anti-malarial natural product cladosporin, we built its complete library of stereoisomers (cladologs) and assessed their inhibitory potential using parasite-, enzyme- and structure-based assays.
We show that potency is manifest via tetrahyropyran ring conformations that are housed in the ribose binding pocket of parasite lysyl tRNA synthetase (KRS). Strikingly, drug potency between top and worst enantiomers varied 500-fold, and structures of KRS-cladolog complexes reveal that alterations at C3 and C10 are detrimental to drug potency where changes at C3 are sensed by rotameric flipping of Glutamate332.
Given that scores of anti-malarial and anti-infective drugs contain chiral centers, this work provides a new foundation for focusing on inhibitor stereochemistry as a facet of anti-microbial drug development.
Cladosporin (12) displays exquisite selectivity for the parasite lysyl-tRNA synthetase over human enzyme. This species specific selectivity of cladosporin has been previously described through comprehensive sequence alignment, where the residues val329 and ser346 seem to be sterically crucial for accommodating the methyl moiety of THP ring10. The structural features of compound 12 clearly indicate the presence of three stereocenters, and therefore 2n (n=3) i.e., eight stereoisomers are possible (Fig.1). Till date, only one asymmetric total synthesis of cladosporin13 has been achieved which was followed by another report of formal syntheses14. Here, we have developed a general chemical synthesis route to synthetically access all the eight possible stereoisomers of compound 12.
cladosporin (compound 12) (0.052 g) as a white solid with a yield of 54 %. Melting point: 171-173 °C; [α]25 D = -15.75 (c = 0.6, EtOH); IR υmax(film): cm-1 3416, 3022, 1656, 1218; 1H NMR (400 MHz, CDCl3): δ 11.06 (s, 1H), 7.47 (br. s., 1H), 6.29 (s, 1H), 6.16 (s, 1H), 4.68 (t, J = 9.8 Hz, 1H), 4.12 (s, 1H), 4.01 (s, 1H), 2.89 – 2.75 (m, 2H), 2.00 – 1.94 (m, 1H), 1.87 – 1.81 (m, 1H), 1.70 – 1.63 (m, 4H), 1.35 (d, J = 6.1 Hz, 2H), 1.23 (d, J = 6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 169.9, 164.3, 163.1, 141.8, 106.7, 102.0, 101.5, 76.3, 68.0, 66.6, 39.3, 33.6, 30.9, 18.9, 18.1; HRMS calculated for C16H21O5 [M + H]+ 293.1384, observed 293.1379.
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Dr. D. Srinivasa Reddy has been appointed as an editor of Bioorganic & Medicinl Chemistry Letters, Elsevier Publications. Congratulation Sir !

Click here for details. https://www.journals.elsevier.com/bioorganic-and-medicinal-chemistry-letters

The research interests of his group lie in issues related to application of oriented organic synthesis, in particular total synthesis of biologically active natural products, medicinal chemistry and crop protection. This team has been credited with having accomplished total synthesis of more than 25 natural products with impressive biological activities. “Some of our recent achievements include identification of potential leads, like antibiotic compound based on hunanamycin natural product for treating food infections, anti-diabetic molecule in collaboration with an industry partner and  anti-TB compound using a strategy called ‘re-purposing of a drug scaffold’,” said Reddy.

A total of two awardees out of four were from CSIR institutes. In addition to Reddy, Rajan Shankarnarayanan, CSIR – CCMB, Hyderabad (basic sciences), also was conferred with the award. Vikram Mathews, CMC, Vellore (medical research) and Prof Ashish Suri, AIIMS, New Delhi (clinical research), were the others to receive the awards.

With more than 80 scientific publications and 35 patents, Reddy is one of the most prominent scientists in the city and has already been honoured with the Shanti Swarup Bhatnagar prize in chemical sciences. Reddy is also a nominated member of the scientific body of Indian Pharmacopoeia, government of India and was  elected as a fellow of the Telangana and Maharashtra Academies of Sciences in addition to the National Academy of Sciences, India (NASI).

//////////CLADOSPORIN, NCL, CSIR, SRINIVASA REDDY, PUNE, MALARIA
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Breaking and Making of Olefins Simultaneously Using Ozonolysis: Application to the Synthesis of Useful Building Blocks and Macrocyclic Core of Solomonamides


Abstract Image

A simple and practical one-pot, two-directional approach to access olefinic esters through simultaneous breaking and making of olefins using ozonolysis of alkenyl aryl selenides is disclosed. The scope of the method with a variety of examples is demonstrated, and the end products obtained here are useful building blocks. As a direct application of the present method, the macrocyclic core of potent anti-inflammatory natural cyclic peptides, solomonamides, is synthesized.

Breaking and Making of Olefins Simultaneously Using Ozonolysis: Application to the Synthesis of Useful Building Blocks and Macrocyclic Core of Solomonamides

CSIR-National Chemical Laboratory, Division of Organic Chemistry, Dr. Homi Bhabha Road, Pune 411008, India
Org. Lett., 2015, 17 (9), pp 2090–2093
DOI: 10.1021/acs.orglett.5b00637
Publication Date (Web): April 14, 2015
Copyright © 2015 American Chemical Society
Figure
GENERAL METHOD
 

Dr. D. Srinivasa Reddy

New route for Expensive drug Ivacaftor synthesis from CSIR-NCL, Pune, India


Cover image for Vol. 2015 Issue 32

Ivacaftor.svg

IVACAFTOR

 

Breaking and Making of Rings: A Method for the Preparation of 4-Quinolone-3-carb­oxylic Acid Amides and the Expensive Drug Ivacaftor

  1. N. Vasudevan,
  2. Gorakhnath R. Jachak and
  3. D. Srinivasa Reddy*

Article first published online: 3 NOV 2015

DOI: 10.1002/ejoc.201501048

http://onlinelibrary.wiley.com/doi/10.1002/ejoc.201501048/abstract

SUPPORTING INFO……….http://onlinelibrary.wiley.com/store/10.1002/ejoc.201501048/asset/supinfo/ejoc_201501048_sm_miscellaneous_information.pdf?v=1&s=2b5b6ac6456ec88f478c07a692e49254e7239f80

 

Abstract

A simple and convenient method to access 4-quinolone-3-carboxylic acid amides from indole-3-acetic acid amides through one-pot oxidative cleavage of the indole ring followed by condensation (Witkop–Winterfeldt type oxidation) was explored. The scope of the method was confirmed with more than 20 examples and was successfully applied to the synthesis of the drug Ivacaftor, the most expensive drug on the market.

 

 

 

REFERENCES

N. Vasudevan, Gorakhnath R. Jachak And D. Srinivasa Reddy, Breaking and Making of Rings: A Method for the Preparation of 4-Quinolone-3-carb­oxylic Acid Amides and the Expensive Drug Ivacaftor, Eur. J. Org. Chem., , 0000 (2015), DOI:10.1002/ejoc.201501048.

http://academic.ncl.res.in/publications/index/select-faculty/2015/ocd

Breaking and Making of Rings: A Method for the Preparation …

onlinelibrary.wiley.com › … › Early View

6 days ago – European Journal of Organic Chemistry … 20 examples and was successfully applied to the synthesis of the drug Ivacaftor, the most expensive …

European Journal of Organic Chemistry – Wiley Online Library

onlinelibrary.wiley.com › … › European Journal of Organic Chemistry

European Journal of Organic Chemistry ….. examples and is successfully applied to the synthesis of the drug Ivacaftor, the most expensive drug on the market.

Breaking and making – Wiley Online Library

onlinelibrary.wiley.com › … › Early View › Abstract

6 days ago – … for the Preparation of 4-Quinolone-3-carboxylic Acid Amides and the Expensive Drug IvacaftorEuropean Journal of Organic Chemistry.

READ ABOUT DR SRINIVASA REDDY at…………

ONE ORGANIC CHEMIST ONE DAY BLOG……..LINK

Dr. Srinivasa Reddy of CSIR-NCL bags the

prestigious Shanti Swarup Bhatnagar Prize

The award comprises a citation, a plaque, a cash prize of Rs 5 lakh

dr

The Shanti Swarup Bhatnagar Prize for the year 2015 in chemical sciences has been awarded to Dr. D. Srinivasa Reddy of CSIR-National Chemical Laboratory (CSIR-NCL), Pune for his outstanding contributions to the area of total synthesis of natural products and medicinal chemistry.
This is a most prestigious award given to the scientists under 45 years of age and who have demonstrated exceptional potential in Science and Technology. The award derives its value from its rich legacy of those who won this award before and added enormous value to Indian Science.
Dr. Reddy will be bestowed with the award at a formal function, which shall be presided over by the honourable Prime Minister. The award, named after the founder director general of Council of Scientific & Industrial Research (CSIR), Dr. Shanti Swarup Bhatnagar, comprises a citation, a plaque, a cash prize of Rs 5 lakh.
Dr. Reddy’s research group current interests are in the field of total synthesis and drug discovery by applying medicinal chemistry. He has also been involved in the synthesis of the agrochemicals like small molecules for crop protection. The total synthesis of more than twenty natural products has been achieved in his lab including a sex pheromone that attracts the mealy bugs and has potential use in the crop protection. On the medicinal chemistry front significant progress has been made by his group using a new concept called “Silicon-switch approach” towards central nervous system drugs. Identification of New Chemical Entities for the potential treatment of diabetes and infectious diseases is being done in collaboration with industry partners.
His efforts are evidenced by 65 publications and 30 patents. He has recently received the NASI-Reliance industries platinum jubilee award-2015 for application oriented innovations and the CRSI bronze medal. In addition, he is also the recipient of Central Drug Research Institute award for excellence in the drug research in chemical sciences and scientist of the year award by the NCL Research Foundation in the year 2013. Dr. Reddy had worked with pharmaceutical companies for seven years before joining CSIR-NCL in 2010.

AN INTRODUCTION

Ph.D., University of Hyderabad, 2000 (Advisor: Professor Goverdhan Mehta).

Post-doctoral with Profs. Sergey A. Kozmin(University of Chicago, USA) and Prof.

Jeffrey Aubé (University of Kansas, USA)

Experienced in leading drug discovery programs (Dr. Reddy’s & TATA Advinus – 7

years of pharma experience)

Acquired skills in designing novel small molecules and lead optimization

Experienced in planning and execution of total synthesis of biologically active

molecules with moderate complexity

One of the molecules is currently in human clinical trials.

MYSELF WITH HIM
s reddy ncl
DEC2014 NCL PUNE INDIA
DR ANTHONY MELVIN WITH DR SRINIVASA REDDY

SILICO LINEZOLID, SILINEZOLID, NDS 10024


Therapeutic options for brain infections caused by pathogens with a reduced sensitivity to drugs are limited. Recent reports on the potential use of linezolid in treating brain infections prompted us to design novel compounds around this scaffold. Herein, we describe the design and synthesis of various oxazolidinone antibiotics with the incorporation of silicon.

Our findings in preclinical species suggest that silicon incorporation is highly useful in improving brain exposures. Interestingly, three compounds from this series demonstrated up to a 30-fold higher brain/plasma ratio when compared to linezolid thereby indicating their therapeutic potential in brain associated disorders

Design, Synthesis, and Identification of Silicon Incorporated Oxazolidinone Antibiotics with Improved Brain Exposure

CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India
Daiichi Sankyo India Pharma Pvt. Ltd., Gurgaon, Haryana 122015, India
§ Incozen Therapeutics Pvt. Ltd., Alexandria Knowledge Park, Turkapally, Rangareddy 500078, India
ACS Med. Chem. Lett., Article ASAP
DOI: 10.1021/acsmedchemlett.5b00213
Publication Date (Web): October 26, 2015
Copyright © 2015 American Chemical Society
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SILINEZOLID, NDS 10024
CAS 1430321-45-1
C18 H26 F N3 O3 Si, 379.50
Acetamide, N-​[[(5S)​-​3-​[4-​(4,​4-​dimethyl-​1-​aza-​4-​silacyclohex-​1-​yl)​-​3-​fluorophenyl]​-​2-​oxo-​5-​oxazolidinyl]​methyl]​-
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Examples from patent

Figure US20140296133A1-20141002-C00027
    (S)—N((3-(4-(4,4-dimethyl-1,4-azasilinan-1-yl)-3-fluorophenyl)-2 oxooxazolidin-5-yl)methyl)acetamide
    NDS 10024
Patent   US20140296133
SEE
AUTHORS
    Preparation of (S)—N((3-(4-(4,4-dimethyl-1,4-azasilinan-1-yl)-3-fluorophenyl)-2 oxooxazolidin-5-yl)methyl)acetamide (12)

  • Figure US20140296133A1-20141002-C00027
  • To a solution of 8 (50 mg, 0.135 mmol) in dimethylformamide (DMF), lithium-t-butoxide (LiOtBu) (32.3 mg, 0.4 mmol) is added. The mixture is stirred at 25° C. for 15 min, followed by the addition of MeOH (0.01 mL, 0.27 mmol). 6 (52 mg, 0.27 mmol) is then added and the reaction mixture is allowed to stir at 25° C. for 24 h. Glacial acetic acid is then added and the organic phase is extracted with EtOAc and washed with brine solution. The crude material is purified by column chromatography on silica gel using hexane-EtOAC mixtures to furnish the pure product 12. The analogous procedure for the corresponding morpholine analogue was adapted from Lu, C. V.; Chen, J. J.; Perrault, W. R.; Conway, B. G.; Maloney, M. T.; Wang, Y. Org. Pro. Res. and Development. 2006, 10, 272-277.
  • 1H NMR (200 MHz, CDCl3): δ 7.33 (d, J=13.8 Hz, 1H), 7.02-6.94 (m, 2H), 6.52 (t, J=5.8 Hz, 1H), 4.77-4.73 (m, 1H), 3.99 (t, J=9.04 Hz, 1H), 3.72 (dd, J=9.0 Hz, 6.8 Hz, 1H), 3.69-3.58 (m, 2H), 3.31 (t, J=5.5 Hz, 4H), 2.01 (s, 3H), 0.89 (t, J=5.5 Hz, 4H), 0.10 (s, 6H). 13C NMR (100 MHz, CDCl3): δ171.2, 155.0 (d, J=244.3 Hz), 154.5, 138.2 (d, J=9.3 Hz), 131.5, 119.9, 114.0 (d, J=3.4 Hz), 107.6 (d, J=27.1 Hz), 71.9, 50.9, 47.7, 41.9, 23.0, 14.3, −2.9.
    Preparation of Bis(bromomethyl)dimethylsilane (2) (as per scheme 2)

  • Figure US20140296133A1-20141002-C00028
  • HBr gas is bubbled to a solution of dimethyl divinylsilane 1 (10.0 g, 89.28 mmols), and dibenzoylperoxide (DBP, 100 mg), in heptane (100 mL) at 0° C. for 30 min. The Reaction mixture (RM) is allowed to stir at room temperature (25° C.) for 18 h, water (200 mL) is added to the reaction mixture and the organic layer is separated. The heptane layer is washed with 2N NaOH (2 100 mL), dried and concentrated to obtain the product 2 as a colourless liquid (24.5 g) in 100% yield.
  • 1H NMR (200 MHz, CDCl3): δ 3.58-3.49 (m, 4H), 1.45-1.40 (m, 4H), 0.09 (s, 6H).
      Preparation of 1-benzyl-4,4-dimethyl-1,4-azasilinane (3)

    • Figure US20140296133A1-20141002-C00029
    • Benzylamine (20 mL, 182 mmol) and Et3N (15.2 mL, 109 mmol) are added to a solution of bis-(bromomethyl) dimethylsilane 2 (10 g, 36.5 mmol) in chloroform (100 mL). The mixture is then refluxed for 16 h. 5% sodiumhydroxide solution (150 mL) is then added and the aqueous layer is extracted with dichloromethane (DCM, 2×100 mL). It is then washed with brine (200 mL), dried and concentrated. The product is purified by column chromatography on silica gel using hexane-EtOAc mixtures to obtain the product 3 as a light yellow liquid (4.3 g) in 54% yield.
    • 1H NMR (200 MHz, CDCl3): δ 7.23-7.35 (m, 5H), 3.66 (s, 2H), 2.68 (t, J=6.3 Hz, 4H), 0.75 (t, J=6.3 Hz, 4H), 0.04 (s, 6H).

Preparation of 4,4-dimethyl-1,4-azasilinane hydrochloride (4)

    • Figure US20140296133A1-20141002-C00030
    • To a solution of 4,4-dimethyl-1,4-azasilinane 3 (2.3 g, 10.5 mmol) in EtOH (20 mL), 6N hydrochloricacid (1.75 mL, 10.5 mmol) is added and the solvent is removed under reduced pressure. The reaction mixture is co-evaporated with EtOH (2×10 mL) and recrystallized from EtOH-diethyl ether. To a slurry of Pd/C (50 mg) in EtOH (15 mL) an ethanolic solution of above prepared HCl salt is added drop wise and stirred at 25° C. under hydrogen atmosphere for 20 h. The reaction mixture is filtered through celite and washed with 2×20 mL of MeOH. The filtrate is then concentrated under reduced pressure to give viscous oil which was triturated with diethyl ether to obtain the product 4 as a white solid (950 mg) in 70% yield.

Preparation of 1-(2-fluoro-4-nitrophenyl)-4,4-dimethyl-1,4-azasilinane (9)

    • Figure US20140296133A1-20141002-C00031
    • To a solution of 4,4-dimethyl-1,4-azasilinane hydrochloride 4 (500 mg, 3.85 mmol) in EtOAc (15 mL), triethylamine (1.3 mL, 9.63 mmol) is added and stirred at 25° C. for 10 min. The reaction mixture is cooled to 0° C. and 3,4-difluoronitrobenzene (612 mg, 3.85 mmol) is added drop wise and allowed to stir at 25° C. for 6 h. Water is then added and the organic layer is separated. The aqueous layer is extracted with EtOAc (2×10 mL) and the solvent is removed under reduced pressure. The product is purified by column chromatography using hexane-EtOAc mixtures and a crystalline yellow solid 9 (721 mg) is obtained in 70% yield.
    • 1H NMR (200 MHz, CDCl3): δ 7.93-7.84 (m, 2H), 6.86 (t, J=4 Hz, 1H), 3.70-3.67 (m, 4H), 0.91-0.85 (m, 4H), 0.12 (s, 6H). 13C NMR (50 MHz, CDCl3): δ 151.1 (d, J=246.71 Hz), 144.4 (d, J=7.13 Hz), 137.8 (d, J=8.59 Hz), 121.4, 115.9 (d, J=4.61 Hz), 113.2 (J=27.78 Hz), 49.4, 13.8, −2.8. IR (CHCl3): ν 2948, 2894, 1603, 1523, 1492, 1400, 1342, 1223, 983, 832, 742 cm−1′. M.P: 70-72° C.

Preparation of benzyl 4-(4,4-dimethyl-1,4-azasilinan-1-yl)-3-fluorophenylcarbamate (10)

    • Figure US20140296133A1-20141002-C00032
    • To a solution of compound 9 (610 mg, 2.28 mmol) in THF (25 mL), Pd/C (30 mg) is added and hydrogenated under a pressure of 35 psi in a par hydrogenator for 8 h. The reaction mixture is filtered through celite. Celite pad is washed with THF (2×20 mL). To the filtrate, saturated NaHCO3 (420 mg, 5.01 mmol) and CBzCl (427 mg, 2.5 mmol) are added at 0° C. and stirred at 25° C. for 5 h. 10 mL water is added to reaction mixture and the aqueous layer is extracted with EtOAc (2×20 mL). The crude mixture is then subjected to column chromatography on silica gel using hexane-EtOAc mixtures to afford the product as a viscous liquid 10 (690 mg) in 82% yield.
    • 1H NMR (200 MHz, CDCl3): δ 7.41-7.37 (m, 5H), 6.94-6.93 (m, 2H), 6.68 (s, 1H), 5.21 (s, 1H), 3.3 (t, J=6.38 Hz, 4H), 0.93 (t, J=6.08 Hz, 4H), −0.13 (s, 6H). 13C NMR (50 MHz, CDCl3): 155.4 (d, 244.4 Hz), 153.6, 136.1, 135.9, 128.6, 128.5, 128.3, 120.4, 117.2 (d, 18.7 Hz), 114.7, 108.3 (20.5 Hz), 67.1, 51.4, 14.4, −3.0. IR (CHCl3): ν 3317, 2953, 2803, 1706, 1594, 1521, 1271, 1221, 1058, 869, 759 cm−1. M.P: 80-82° C.

Preparation of (S)-5-(aminomethyl)-3-(4-(4,4-dimethyl-1,4-azasilinan-1-yl)-3-fluorophenyl)oxazolidin-2-one (11) (NDS-10057)

    • Figure US20140296133A1-20141002-C00033
    • To a solution of 10 (1.20 g, 3.23 mmol) and (S)-tert-butyl 3-chloro-2-hydroxypropylcarbamate (1.35 g, 6.47 mmol) in DMF (10 mL), LiOtBu (1.03 g, 12.94 mmol) is added at 0° C. The mixture is stirred at 25° C. for 45 h. The starting material 10 is not consumed completely. Saturated NH4Cl is then added; the organic phase is extracted with EtOAc (2×20 mL), washed with brine solution, dried and concentrated. The crude residue is dissolved in 20 mL of DCM-TFA mixture (8:2) and stirred at 25° C. for 3 h. RM is concentrated and dissolved in water (10 mL), the aqueous layer is washed with diethyl ether (2×50 mL), basified with saturated NaHCO3 and extracted with DCM (2×50 mL). The DCM layer is dried and concentrated. The crude is purified by column chromatography on silica gel using hexane-EtOAc mixtures to obtain the product as an off-white solid (500 mg) in 45% (based on recovery of starting material) over 2 steps.
    • 1H NMR (400 MHz, CDCl3): δ 7.36 (dd, J=14.2 Hz, 2.3 Hz, 1H), 7.09 (dd, J=8.8 Hz, 1.7 Hz, 1H), 6.96 (t, J=9.5 Hz, 1H), 4.72-4.59 (m, 1H), 4.00 (t, J=8.3 Hz, 1H), 3.79 (dd, J=8.7 Hz, 6.8 Hz, 1H), 3.30 (t, J=6.2 Hz, 4H), 3.03 (dq, J=13.6 Hz, 4.2 Hz, 2H), 0.90 (t, J=6.2 Hz, 4H), 0.10 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 155.1 (d, J=244.3 Hz), 154.7, 137.9 (d, J=9.0 Hz), 132.1 (d, J=10.3 Hz), 112.0 (d, J=4.3 Hz), 113.8 (d, J=3.2 Hz), 107.4 (d, J=26.9 Hz), 73.8, 51.0, 47.8, 45.01, 14.4, −2.9. IR (CHCl3): ν 3685, 3021, 2955, 2809, 2401, 1747, 1515, 1416, 1219, 1029, 991, 870, 771, 667 cm−1. M.P: 94-96° C. ESI-MS: 360.11 (M+Na).

Preparation of (S)—N-((3-(4-(4,4-dimethyl-1,4-azasilinan-1-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methy)acetamide (12) (NDS 10024)

  • Figure US20140296133A1-20141002-C00034
  • To solution of amine 11 (300 mg, 0.9 mmol) and DIPEA (0.3 mL, 1.78 mmol) in dry THF (4.0 mL), acetylchloride (0.08 mL, 1.07 mmol) is added at 0° C., and stirred at 25° C. for 3 h. Further, saturated NaHCO3 (5.0 mL) is added to the reaction mixture and extracted with EtOAc (2×5 mL). The organic layer is washed with brine, dried and concentrated. The product is purified by column chromatography on silica gel using hexane-EtOAc mixtures to obtain the product as an off-white solid (170 mg) in 50% yield.
  • 1HNMR (400 MHz, CDCl3): δ 7.33 (d, J=13.8 Hz, 1H), 7.02-6.94 (m, 2H), 6.52 (t, J=5.8 Hz, 1H), 4.77-4.73 (m, 1H), 3.99 (t, J=9.04 Hz, 1H), 3.72 (dd, J=9.0 Hz, 6.8 Hz, 1H), 3.69-3.58 (m, 2H), 3.31 (t, J=5.5 Hz, 4H), 2.01 (s, 3H), 0.89 (t, J=5.5 Hz, 4H), 0.10 (s, 6H). 13C NMR (100 MHz, CDCl3): δ171.2, 155.0 (d, J=244.3 Hz), 154.5, 138.2 (d, J=9.3 Hz), 131.5, 119.9, 114.0 (d, J=3.4 Hz), 107.6 (d, J=27.1 Hz), 71.9, 50.9, 47.7, 41.9, 23.0, 14.3, −2.9. IR (CHCl3): ν 2401, 1759, 1675, 1519, 1216, 759, 669 cm−1 M.P: 123-126° C. ESI-MS: 380.10 (M+H).
SCHEME 1
  • Figure US20140296133A1-20141002-C00015
    Figure US20140296133A1-20141002-C00016

SCHEME2

  • Figure US20140296133A1-20141002-C00018
    Figure US20140296133A1-20141002-C00019

SCHEME 3

  • Figure US20140296133A1-20141002-C00020

SCHEME 4

  • Figure US20140296133A1-20141002-C00021

str1

str1

Dr. D. Srinivasa Reddy of NCL winner Shanti Swarup Bhatnagar Award 2015

see

http://oneorganichemistoneday.blogspot.in/2015/02/dr-d-srinivasa-reddy.html

Dr. Srinivasa Reddy of CSIR-NCL bags the

prestigious Shanti Swarup Bhatnagar Prize

The award comprises a citation, a plaque, a cash prize of Rs 5 lakh

dr

The Shanti Swarup Bhatnagar Prize for the year 2015 in chemical sciences has been awarded to Dr. D. Srinivasa Reddy of CSIR-National Chemical Laboratory (CSIR-NCL), Pune for his outstanding contributions to the area of total synthesis of natural products and medicinal chemistry.
This is a most prestigious award given to the scientists under 45 years of age and who have demonstrated exceptional potential in Science and Technology. The award derives its value from its rich legacy of those who won this award before and added enormous value to Indian Science.
Dr. Reddy will be bestowed with the award at a formal function, which shall be presided over by the honourable Prime Minister. The award, named after the founder director general of Council of Scientific & Industrial Research (CSIR), Dr. Shanti Swarup Bhatnagar, comprises a citation, a plaque, a cash prize of Rs 5 lakh.
Dr. Reddy’s research group current interests are in the field of total synthesis and drug discovery by applying medicinal chemistry. He has also been involved in the synthesis of the agrochemicals like small molecules for crop protection. The total synthesis of more than twenty natural products has been achieved in his lab including a sex pheromone that attracts the mealy bugs and has potential use in the crop protection. On the medicinal chemistry front significant progress has been made by his group using a new concept called “Silicon-switch approach” towards central nervous system drugs. Identification of New Chemical Entities for the potential treatment of diabetes and infectious diseases is being done in collaboration with industry partners.
His efforts are evidenced by 65 publications and 30 patents. He has recently received the NASI-Reliance industries platinum jubilee award-2015 for application oriented innovations and the CRSI bronze medal. In addition, he is also the recipient of Central Drug Research Institute award for excellence in the drug research in chemical sciences and scientist of the year award by the NCL Research Foundation in the year 2013. Dr. Reddy had worked with pharmaceutical companies for seven years before joining CSIR-NCL in 2010.

AN INTRODUCTION

Ph.D., University of Hyderabad, 2000 (Advisor: Professor Goverdhan Mehta).

Post-doctoral with Profs. Sergey A. Kozmin(University of Chicago, USA) and Prof.

Jeffrey Aubé (University of Kansas, USA)

Experienced in leading drug discovery programs (Dr. Reddy’s & TATA Advinus – 7

years of pharma experience)

Acquired skills in designing novel small molecules and lead optimization

Experienced in planning and execution of total synthesis of biologically active

molecules with moderate complexity

One of the molecules is currently in human clinical trials.

MYSELF WITH HIM

s reddy ncl
DEC2014 NCL PUNE INDIA
DR ANTHONY WITH DR REDDY

OTHER AUTHORS

Remya Ramesh

Remya Ramesh

M.Sc Applied Chemistry
Senior Researcher
Seetharamsingh Balamkundu
Pankaj Khairnar
Srikant Viswanadha

Srikant Viswanadha

Ph.D.
Vice President
Incozen Therapeutics Pvt. Ltd. · Drug Discovery

////////

C[Si]1(C)CCN(CC1)c2ccc(cc2F)N3C[C@H](CNC(C)=O)OC3=O

At Scientific Update Organic Process Research and Development Conference, NCL, PUNE, INDIA, 5 TH DEC 2014


WP_000231

I am seated left with DR PAUL MURRAY, DR JOHN KNIGHT, DR WILL WATSON, At Scientific Update Organic Process Research and Dev Conference, NCL, PUNE ,INDIA, 5 TH DEC 2014

WP_000228

DR WILL AND DR JOHN IN A DISCUSSION

WP_000235

A SLIDE

PROCESS CHEMISTRY CONFERENCES SCHEDULE

EVENT

Organic Process Research & Development - India

Title:
Organic Process Research & Development – India
Subtitle:
The 32nd International Conference and Exhibition
When:
04.12.2014 – 05.12.2014
Where:
National Chemical Laboratory – Pune
Brochure:
View Brochure

http://scientificupdate.co.uk/conferences/conferences-and-workshops/details/224-organic-process-research-and-development-conference-india.html

WP_000230

poster by DR PRAVIN KENDREKAR

PUNE CITY

NCL

MUMBAI PUNE EXPRESSWAY

PUNE FC

 

Volkswagen India Plant and offices in Pune

From top: Fergusson College, Mahatma Gandhi Road(left), Shaniwarwada (right), the HSBC Global Technology India Headquarters, and the National War Memorial Southern Command

From top: Fergusson College, Mahatma Gandhi Road (left), Shaniwarwada (right), the HSBC Global Technology India Headquarters, and the National War Memorial Southern Command

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