APURBA BHATTACHARYA

 

HOME                                                                      LABORATORY
301 Cape Aron                                                         Department of Chemistry
Corpus Christi, Texas 78412                                     Tx A&M University
(361) 994-9057                                                        MSC 161, Kingsville, Texas 78363
                                                                                 (361) 593-2664 [kfab002@tamuk.edu]

EDUCATION

Ph.D. Organic Chemistry, University of Texas at Austin: 1982
M.S. Chemistry, Indian Institute of Technology. Kanpur, India: 1976
B.S. Chemistry, Calcutta University, India: 1974

EMPLOYMENT

1999- present          Assistant Professor, Texas A&M University, Kingsville.
1997-1999              Group Leader, Bristol Myers Squibb, Central Process Research
1995-1997              Lead Chemist; Innovator Group, Hoechst.
1994-1995:             Staff Chemist, Hoechst-Celanese.
1990-1994:             Senior Research Chemist, Hoechst-Celanese.
1988-1990:             Research Fellow, Process Research and Development, Merck &          Co., Inc.
1983-1988              Senior Research Chemist, Process Research and Development,             Merck & Co., Inc.

CONSULTANT: Scientific Process Advisor: PHARM-ECO A Johnson Matthey Company. 2001- Present.

ACADEMIC EXPERIENCE

      Graduate Research Assistant, (1977-1982), Professor James K. Whitesell. Department of Chemistry, University of
      Texas at Austin. Asymmetric induction in carbon-carbon bond forming reaction was studied.
      Very high asymmetric induction (92-99%) were achieved in the nucleophilic addition of chiral glyoxylate and pyruvate
      esters as well as concerted "-ene" and cycloaddition reactions.
      Kinetic resolutions of simple olefins were accomplished via asymmetric "-ene" reactions.
      Intramolecular Diels-Alder reactions were exploited for asymmetric synthesis of a natural product , antibiotic
      "X-14547A"

       Teaching Assistant     Undergraduate organic chemistry laboratory.

 INDUSTRIAL EXPERIENCE

Discovered and developed novel silicon mediated quinone oxidation of aza-steroids successfully implemented for the production of PROSCARTM / PROPECIATM and other benign prostatic hypertrophy (BPH)-candidates.

Process Research and Development designing novel, practical and cost-effective synthesis of drug candidates from bench scale to commercialization.
Introduced efficient chiral phase-transfer technology to prepare either enantiomer of the drug candidate L-644, 711.

Devised and devoloped a unique amphoteric copolymer derived from vinylpyridine and acetoxystyrene.

Discovered and developed a waste-free synthesis of chiral ibuprofen via unprecedented diastereoreversal.

Discovered and developed a synthesis of D-p-hydroxyphenylglycine via a novel crystallization induced asymmetric transformation.

Identified and developed a new synthesis of 2-alkyl indanones.

Devised and developed a synthesis of cromolyn sodiumTM

Identified and developed a novel synthesis of 4-quinazolinones as pharmaceutical intermediates.

 Involved in the development from bench scale to commercialization of a 20-step synthesis of Gd/Lu Texaphyrin, agent for MRI imaging, photosensitizer and photodynamic therapy of cancer.

 AWARDS

        Robert A.Welch Fellowship
        Phi Kappa Phi Fellowship for academic excellence.
        Outstanding teaching assistant award (1980)
        National Scholarship (India)  

PROFESSIONAL ACTIVITIES

American Chemical Society
Merck and Hoechst ambassador in University of Texas at Austin , Houston and
Texas A & M University.

 PUBLICATIONS

 
      1.   "Asymmetric Induction, Nucleophilic Addition to a Chiral Glyoxylate Ester", Whitesell, J. K.; Bhattacharya, A. ; and
       Henke, K., J. Chem. Soc. Chem. Commun., 988-89 (1982).

2.   "Asymmetric Induction. Ene Reactions of a Chiral Glyoxylate Ester", Whitesell, J. K.; Bhattacharya, A.; Aguilar, D. A.; and Henke, K., J. Chem. Soc. Chem. Commun., 17, 989-90 (1982)

3.   "A Glimpse Towards Asymmetric Induction", Bhattacharya, A., Diss. Abstr. Int. B, 43 (12, pt. 1), 3980 (1983)

4.   "Asymmetric Induction. Reduction, Nucleophilic Addition to and Ene Reaction of Chiral Alpha-Keto Esters", Whitesell, J. K.; Bhattacharya, A.; and Deyo, D., J  Chem. Soc. Chem. Commun., 15, 802 (1983)

5.   "Efficient Catalytic Asymmetric Alkylations. 2. Chiral Robinson Annulations via Phase-Transfer Catalysis", Bhattacharya, A.; Dolling, U.-H.; Grabowski, E. J. J.; Karady.; Ryan, K. M.; Weinstock, L. M., Angew. Chem., 98, 442-443 (1986)

6.   "Asymmetric Induction in the Ene Reaction of a Glyoxylate Ester of S-Phenyl Menthol", Whitesell, J. K.; Bhattacharya, A.; Chen, H. H.; Deyo, D.; James, D.; and Liu, C. L., Tetrahedron, 42 (11), 2993-3001 (1986).

7.   "Efficient Asymmetric Alkylations via Chiral Phase-Transfer Catalysis: Applications and Mechanism", Dolling, U.-H.; Hughes, D. L.; Bhattacharya, A.; Ryan, K. M.; Karady, S.; Weinstock, L. M.; and Grabowski, E. J. J., In: Starks, C. M., Editor, "Phase Transfer Catalysis; New Chemistry, Catalysts, and Applications, Chapter 7", ACS  Symp. Ser., 326, 67-81 (1987).

8.   "Efficient Asymmetric Alkylations via Chiral Phase-Transfer Catalysis. A Novel Dual Catalysis." Dolling, U.-H.; Hughes, D. L.; Bhattacharya, A.; Ryan, K. M.; Karady, S.; Weinstock. L. M.; Grenda, V. J.; and Grabowski, E. J. J., Catalysis of Organic Reactions, [edited by Paul N. Rylander, Hatedd Greenfield and Robert L. Augustine], 33, 65-86 (1988).

9.   "Silylation-Mediated Oxidation of 4-Aza-3-Ketosteroids with DDQ Proceeds via DDQ-Substrate Adducts", Bhattacharya, A.; DiMichele, L. M.; Dolling, U.-H.; Douglas, A. W.; and Grabowski, E. J. J.,  J. Am. Chem. Soc., 110, 3318-19 (1988).

10."DDQ Oxidation of Silyl Enol Ethers to Enones Proceeds via DDQ-Substrate Adducts", Bhattacharya, A.; DiMichele, L. M.; Dolling, U.-H.; Grabowski, E. J. J.; Grenda, V. J., J. Org. Chem., 54,6118-6120 (1989).

11."Silicon Assisted Quinone Oxidations Proceeds via Quinone-Substrate Adducts". Merck Speakers Program Brochure 1989-1990.

12. "Proscar ®" Merck Index, eleventh edition, 7888, 1989.

13. "Oxidation of 4-Aza-3-Ketosteroids". Bhattacharya, A., Centennial Year Edition, MSDRL Selected Publications.

14. "Acylimidazolides as Versatile Synthetic Intermediates for the Preparation of Sterically Congested Amides and Ketones: A Practical Synthesis of Proscar" Bhattacharya, A.; Williams, J. M.; Amato, J. S.; Dolling, U.-H.; and Grabowski, E. J. J., Synthetic Communications 30(17), 2683-2690, 1990.

15. "Crystallization Induced Asymmetric Transformation: Synthesis of D-p-Hydroxyphenylglycine" Bhattacharya, A.; Aruallo-Mcadams, C.; and Meier, M. B., Synthetic Communications, 24(17), 2449-2459, 1994.

16. "Methyl Glyoxylate" Encyclopedia of Reagents for Organic Synthesis (EROS), Bhattacharya, A.1994.

17. "Phenmenthyl Glyoxylate" Encyclopedia of Reagents for Organic Synthesis (EROS),  Bhattacharya, A. 1994.

 

PRESENTATIONS

 

1.   "Efficient Asymmetric Alkylations via Chiral Phase-Transfer Catalysis". For presentation at : American Chemical Society 190th National Meeting, Chicago, Illinois,9/8/85-9/13/85.

2.   "Quarternary Ammonium Ions Derived From Cinchona Alkaloids as Chiral Phase-Transfer Alkylation Catalysts: Appilations and mechanisms".: Hetrocyclic Chemistry 10th International Congress, Waterloo, Ontario, Canada, 8/11/85-8/16/85.

3.   "Efficient Asymmetric Alkylations via Chiral Phase-Transfer Catalysis. A Novel Dual Catalysis".: Organic Reactions Catalysis Society Eleventh Meeting, Savannah, Georgia, 4/6/86-4/8/86.

4.   "Recent  Mechanistic Studies on The Mitsunobo reaction and DDQ-Mediated double bond introduction".: Gordon Research Conference on Organic Reactions and Processes, New Hampshire, 7/13/87-7/18/87.

5.   "Quinone Oxidation in Synthesis;Fascination New Mechanistic Aspects".: U.of Texas at Austin, Austin, Texas, November 5, 1987.

6.   "Silicon Assisted Quinone Oxidation: Mechanisms and application to aza-steroid synthesis".: U. of Houston, Houston, Texas, November 6, 1987.

7.   "Quinone Oxidation: Mechanism and application in steroid synthesis".: Texas A&M Univ. College Station, Texas, November 9, 1987.

8.   "Silylation Mediated Quinone oxidation".: Merck-Bucknell Symposium, March 16, 1988.

9.   "Oxidation of Lactum Derived TMS-Imidates With Quinones Proceeds Via Unprecedented Quinone-Substrate Adducts".: Heterocyclic Chemistry 12th International Congress, Jerusalem, Israel, 8/13/89-8/17/89.

10. "Synthesis of D1-4-Aza Steroids via Silylation Mediated Quinone Oxidation".: Lakeland Heterocyclic symposium, Grasmere.Royal Society of Chemistry: Perkin Division May 4-8 1989.

11."Quinone Oxidation of TMS Imidates and Enolethers Proceeds via Single Electron Tranlfer".:32nd IUPAC Congress Stockholm,2-7 August 1989.

12. “Development of Finastride”.: 20001 4th Annual Howard Radwin Urology Conference San Antonio Texas October 19-20, 2001

13. “Environmentally Friendly Solvent-Free Processes: Preparation of Nitro Alcohols, A Class of Valuable Drug Intermediates by Henry Reaction”.: American Chemical Society 57th Southwest Regional Meeting October 17-20, 2001.

 

PATENTS

 

1.   "An Enantiomer of a Substituted Fluorenyloxy Acetic Acid": U.S.4606760.

2.   "Enantiomers of a Substituted Fluorenyloxy Acetic Acid": EP-176947.

3.   "Preparation of Enantiomers of a Substituted Fluorenyloxy Acetic Acid": U.S. 45857357.

4.   "Steroid Dehydrogenation Process Intermediates" : U.S. 5116983.

5.   "Dehydrogenation of Azasteroids" : U.S. 5084574.

6.   "Preparation of 4-Azo-chol-1-ene-3, 20-dione derivatives as testosterone reductase inhibitors" EP-367502.

7.   "Process for the dehydrogenation of 3-oxo steroids (and especially 3-oxo-4aza steroids) in the 1,2-position using quinones and silylating agents, and quinone-steroid adduct intermediates" EP-298652.

8.   "Amphoteric Copolymer Derived from Vinylpyridine and Acetoxystyrene" U. S. 5210149.

9.   "Amphoteric Copolymer Derived from Vinylpyridine and Acetoxystyrene" U. S. 5304610.

10."Precipitation-Induced Asymmetric Transformation of Chiral Alpha-Amino Acids and salts thereof" EP-499376.

11."Racemization of an Enantiomerically Enriched a-Aryl Carboxylic Acid" U.S. 5332834.

12."Selective Precipitation of alpha arylcarboxylic acid salts" U.S. 5380867.

13."Process for the Productton of Calcium Salts of Hydantoic Acid. U.S.5338859.

14."Selective Precipitation of a arylcarboxylic acid salts" U.S. 5399707.

15."Process for preparing cyclic ketones" U.S. 5489712.

16. “Process for the preparation of dialkali metal cromoglycates” U.S. 5,508,451

17. “Preparation of 4-quinazolinones from N-acyl-b-aminoacids” U.S. 96-596794.

18. “Preparation of 5,6-dihydro-3H-pyrimidin-4-one derivatives” U.S. 96-595885.

19. “Three step process for preparing anthranilic acids from aniline” U.S. 96-593536.

20. “Process for azole antifungal intermediates” U.S. 6,326,509, Dec.4, 2001.

 

RESEARCH INTERESTS:

Organic Chemistry and Environmental Chemistry.

Pharmaceutical Process Research and Development.

 

Process chemistry, the practice of scaling up chemical production from gram and kilograms to thousands of gallons while always of vital importance, has lately become a highly visible enterprise in the pharmaceutical sector. In the pharmaceutical industry, once the medicinal chemist defines the target molecule, the process chemist finds the most efficient, economical and safe route to make the molecule and its analogues. We have established collaborative programs with several leading pharmaceutical companies (e.g. Bristol-Myers Squibb Pharmaceuticals Research Institute, and Dannier Chemical, Inc) whereby the research students will be involved in identifying and solving process related problems and issues of potential mutual interest. This involves synthesizing initial quantities of drug candidates using the existing-route as well as improving the existing synthesis, possibly following a completely different strategy from the medicinal route so that it can be scaled up for commercial production.

 Environmentally Benign Processes in Organic Synthesis.

 Over the past few years significant amount of research activities in the chemical community have been directed towards the development of new technologies and methodologies for environmentally benign processes. This area of chemistry has received extensive attention and is often referred to as "green chemistry". "Green chemistry" focuses on the design, manufacture, and use of chemicals and processes that have little or no pollution potential or environmental risk and are both economically and technologically feasible. The principle of green chemistry can be applied to broad areas of chemistry including synthesis, catalysis, reaction conditions, separations, analysis and monitoring. Green Chemistry differs from conventional chemistry in several different categories including nature of starting materials, reagents, reaction conditions and target molecule. The scope of Research and Development in this area is enormous. We intend to concentrate on the following specific areas of chemistry.

1. Solvent Minimization. Most organic reactions are performed in presence of organic solvents. A reaction, which is performed without addition of any solvent, has several advantages. The cost of processing (adding the solvent and its subsequent removal), handling and disposal of the solvent is completely eliminated. Performing the reaction neat without any solvent also results in significant improvement in throughput or process efficiency.

2. Reactions on Solid Support; Waste-free Catalytic Technology. A number of chemical processes use either stoichiometric
    acidic or basic conditions resulting in the production of stoichiometric amount of waste salt. Importantly, inorganic salts
    account for the bulk of industrial chemical waste. Besides polluting soil and ground water, salts can lower the pH of
    atmospheric moisture and have been implicated in the formation of acid-dew. Designing chemical processes which utilizes
    only catalytic amount of acid/base (via regeneration of the catalyst) or enables separation of the catalyst by simple filtration
    and reuse would minimize waste formation.

3. Organic Reactions in Water. Recently there has been increasing interest in the use of water as a medium for organic
    applications. Utilizing of water as reaction medium for organic substrate would minimize the formation of enormous amounts
    of organic waste. Even simple organic reactions (e.g. Diels Alder reactions, Claisen rearrangements and nucleophilic
    additions) in water solutions can show hydrophobic effects on rates and selectivity’s if nonpolar segments of the reactants are
    brought together in the TS.

4. Atom Economy. This concept was elucidated and demonstrated by Trost. The improvement of synthetic efficiency requires
    the development of more reactions wherein the product is the sum of the reactants with anything else being required only
    catalytically, namely, atom economic processes.

5. Energy Conservation: Application of Microwave and Sonication in Organic Synthesis. Significant acceleration of organic
    reactions can be achieved by the use of both microwave as well as ultlasonication technology. In order for these processes to
    be practical the reaction units have to be engineered to operate reliably and safely on a routine basis preferably in a
    continuous or semi-continuous mode.

6. Chiral Phase-Transfer Catalysis. Catalytic asymmetric synthesis with high enantioselectivity and nearly quantitative chemical
    yield via chiral phase-transfer catalysis (PTC) will be applied to the synthesis of pharmaceuticals. The chiral PTC technology
    offers potential as a pseudo-enzymic process in organic synthesis in terms of simplicity, ease of operation, and
    enantiospecificity.