Steven John Cianciosi

US Patent:

6482952, Nov 19, 2002

Filed:

Jun 18, 2001

Appl. No.:

09/883417

Inventors:

Steven J. Cianciosi - Leesburg GA
Gregory L. Tewalt - Lansdale PA
Eric T. Pisk - Harrisonburg VA
Ilia A. Zavialov - East Windsor NJ
Glenn A. Hulvey - Harrisonburg VA

Assignee:

Merck Co., Inc. - Rahway NJ

International Classification:

C07D26352

US Classification:

548217

Abstract:

Acetonides are obtained in a one-step reaction of a carboxylic acid halide, a 1,2-aminoalcohol, and 2-alkoxypropene or 2,2-dialkoxypropane in an ether solvent and in the presence of an inorganic base. Acetonides are also obtained in a two-step reaction scheme in which an acid halide and 1,2-aminoalcohol are reacted in an ether solvent in the presence of LiOH to form a hydroxyamide, which is then reacted with 2-alkoxypropene or 2,2-dialkoxypropane in the presence of acid to form the acetonide. The acetonides resulting from the one-step and two-step protocols can be further reacted with an allylating agent such as an allyl halide in the presence of a strong base to provide the corresponding allyl acetonide. The acetonides and allyl acetonides can serve as intermediates in the production of certain HIV protease inhibitors which are useful for treating HIV infection and AIDS.

US Patent:

52234150, Jun 29, 1993

Filed:

Feb 7, 1992

Appl. No.:

7/832545

Inventors:

Michael J. Conder - Harrisonburg VA
Steven J. Cianciosi - Harrisonburg VA
William H. Cover - Lansdale PA
Rebecca L. Dabora - Andover MA
Eric T. Pisk - Harrisonburg VA
Robert W. Stieber - Harrisonburg VA
Bogdan Tehlewitz - McGaheysville VA
Gregory L. Tewalt - Shenandoah VA

Assignee:

Merck & Co., Inc. - Rahway NJ

International Classification:

C12P 1700
C12P 1706
C12N 914
C07D30930

US Classification:

435125

Abstract:

Biosynthetic production of 7-[1',2',6',-7',8',8a'(R)-hexahydro-2'(S),6'(R)-dimethyl-8'(S)-hydroxy-1'( S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid, "triol acid", is accomplished by enzymatic hydrolysis of lovastatin acid or a salt thereof, by treating it with Clonostachys compactiuscula ATCC 38009 or ATCC 74178, or mutants thereof, or a cell-free extract derived therefrom, or a hydrolase derived therefrom. The triol acid and its lactone form are both inhibitors of HMG-CoA reductase and thus useful as anti-hypercholesterolemic agents, and may also serve as intermediates for preparation of other HMG-CoA reductase inhibitors. Also, in the synthesis of simvastatin by direct methylation of lovastatin, selective hydrolysis of residual lovastatin salt by treatment with Clonostachys compactiuscula ATCC 38009 or ATCC 74178 or mutants thereof or a cell-free extract derived therefrom, or a hydrolase derived therefrom yields the "triol" salt which can be easily separated from simvastatin.

US Patent:

55084044, Apr 16, 1996

Filed:

Mar 15, 1995

Appl. No.:

8/404776

Inventors:

David Askin - Warren NJ
Steven J. Cianciosi - Harrisonburg VA
Robert S. Hoerrner - Scotch Plains NJ

Assignee:

Merck & Co., Inc. - Rahway NJ

International Classification:

C07D40106

US Classification:

544365

Abstract:

A process of reductive amination efficiently yields an HIV protease inhibitor.