Synthetic Studies toward Ecteinascidin 743

An efficient synthesis of a fully functionalized tetracyclic fragment (A-B-C-H) I of ecteinascidin 743, contg. a 1,4-bridged 10-membered lactone, is reported. The synthesis is highly convergent and has been carried out on a multigram scale featuring the following key steps: union of two fragments II and III via an oxazolidine intermediate; and acid-promoted macrocyclization via formation of a carbon-sulfur bond with concomitant formation of the 10-membered ring. Although compd. I was responsive to the intramol. Pictet-Spengler reaction, a destructive ring opening of the 1,4-bridged lactone also occurred, leading to the formation of pentacyclic compd. IV. In the course of this study, it was discovered that a combination of a mild Lewis acid and a mild Bronsted acid constituted excellent reagents for performing the Pictet-Spengler reaction of a highly acid-sensitive substrate. [on SciFinder (R)]

Published in:
Journal of Organic Chemistry, 70, 11, 4397-4408
CAN 143:60125
Institut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.
written in English.
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 Record created 2010-11-25, last modified 2018-03-17

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