Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing heterocyclic carbon compound having only o – n – s,...
Patent
1992-02-07
1993-06-29
Robinson, Douglas W.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing heterocyclic carbon compound having only o, n, s,...
435117, 435 41, 435183, 435195, 549292, C12P 1700, C12P 1706, C12N 914, C07D30930
Patent
active
052234150
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.
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Cianciosi Steven J.
Conder Michael J.
Cover William H.
Dabora Rebecca L.
Pisk Eric T.
Caruso Charles M.
Dolan Catherine A.
Lankford L. Blaine
Merck & Co. , Inc.
Robinson Douglas W.
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