1.5- Benzothiazepines, 2,5-dihydro 2-hydroxy

Benzothiazepines belong to the three classes of calcium channel blockers which are important cardiovascular drugs in the management of angina pectoris and hypertension. A diastereoselective one-pot synthesis of the trans-and ds-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-l,5-benzothiazepin-4-one nucleus, a key intermediate in the preparation of the calcium channel blocker Diltiazem, was carried out under microwave irradiation in an open vessel (Scheme 25). Control of the diastereoselectivity was achieved by vary-... 

Diltiazem hydrochloride has also been known as (+)-cis-3-(acetyloxy)-5-[2-(dimethylamino)ethylJ-2,3-dihy-dro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one monohydrochloride and (+)-5-[2-(dimethylamino)ethyl]-cis-2>3-dihydro-3-hydroxy-2-(p-methoxyphenyl)-1,5-benzothia-zepin-4(5H)-one acetate (ester) monohydrochloride. 

A different protocol for the asymmetric synthesis of 3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-l,5-benzothiazepin-4(5//)-one has been disclosed <05H147>. The novelty in this procedure resides in the use of bakers yeast to reduce P-arylthio-a-keto ester precursors to the corresponding hydroxy esters in fair yields and reasonable stereoselectivities (diastereomer ratios and ee s). 

Dimethylamino)ethyl]-cis-2,3-dihydro-3-hydroxy-2-(p-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one acetate (ester). 

Kometani T, Sakai Y, Matsumae H, Shibatani X Matsuno R. Production of (2S,3S)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-l,5-benzothiazepin-4(5H)-one, a key intermediate for diltiazem synthesis, by bakers yeast-mediated reduction. /. Terment. Bioeng. 1997 84 195-199. 

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