| Abstract
| - A practical stereocontrolled synthesis of (+)-discodermolide (1) has been completed in 10.3% overallyield (23 steps longest linear sequence). The absolute stereochemistry of the C1−C6 (7), C9−C16 (8), andC17−C24 (9) subunits was established via substrate-controlled, boron-mediated, aldol reactions of the chiralethyl ketones 10, 11, and 12. Key fragment coupling reactions were a lithium-mediated, anti-selective, aldolreaction of aryl ester 8 (under Felkin-Anh induction from the aldehyde component 9), followed by in situreduction to produce the 1,3-diol 40, and a (+)-diisopinocampheylboron chloride-mediated aldol reaction ofmethyl ketone 7 (overturning the inherent substrate induction from the aldehyde component 52) to give the(7S)-adduct 58. The flexibility of our overall strategy is illustrated by the synthesis of a number of diastereomersand structural analogues of discodermolide, which should serve as valuable probes for structure−activity studies.
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