SYNTHESIS OF THE LIPOPHILIC SIDE-CHAIN OF THE CYCLIC HEXADEPSIPEPTIDE ANTIBIOTIC L-156,602

The 14-carbon tetrahydropyranylpropionic acid side chain of the cyclic hexadepsipeptide antibiotic L-156,602 (1) has been prepared as the methyl ester derivative 5. Asymmetric synthesis of the key intermediate 11-carbon lactone 7 was accomplished using diastereoselective alkylation of the alkoxide enolate of methyl (R)-3-hydroxybutanoate. A second route to lactone 7 utilized sequential organometallic reactions of the pinanediol boronic ester 17 to control two chiral centers. The enolate of the chiral dioxolanone 6 condensed with lactone 7 to produce the complete 14-carbon skeleton as a single diastereomer. © 1990, American Chemical Society. All rights reserved.