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Applications of Lewis acids for the efficient syntheses of diltiazem, cephems, and taxoids
Author(s) -
Hashiyama Tomiki
Publication year - 2000
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/1098-1128(200011)20:6<485::aid-med3>3.0.co;2-s
Subject(s) - taxoid , cephem , chemistry , diltiazem hydrochloride , stereoselectivity , lewis acids and bases , catalysis , ring (chemistry) , tin , combinatorial chemistry , transmetalation , stereochemistry , diltiazem , reactivity (psychology) , medicinal chemistry , organic chemistry , calcium , medicine , carboxylic acid , alternative medicine , surgery , chemotherapy , pathology , paclitaxel
Abstract An efficient method is described for preparation of diltiazem hydrochloride (Herbesser®), a marketed calcium antagonist widely used for the treatment of ischemic heart disease. In the reaction of 2‐nitrothiophenol ( 1 ) with trans ‐3‐phenylglycidic esters ( 2 ) carrying various substituents on the benzene ring, both reactivity and stereoselectivity of the oxirane ring‐opening of the glycidates were markedly influenced by the electronic nature of the substituents. As a result of our investigation on the catalytic effect of various Lewis acids in the reaction of 2a with 1 , tin compounds were found to be effective catalysts for the cis ‐opening and readily produced the threo ‐nitro ester ( 3a‐ t ), a key intermediate for the synthesis of diltiazem. Isolation of the crystalline complex from the reaction of 1 and SnCl 4 ; and its efficient catalytic activity similar to that of SnCl 4 suggests that the transition state involves co‐coordination of tin derivatives both with 1 and the epoxy oxygen of 2a to result in highly specific cis ‐opening. We have also amplified this chemistry into other fields, leading to applications in the syntheses of cephem and taxoid templates. © 2000 John Wiley & Sons, Inc. Med Res Rev, 20, No. 6, 485–501, 2000