Soluble polymer-supported chemoenzymatic synthesis of the C(21)-C(27) fragment of the bryostatins.
A chemoenzymatic synthesis of the C(21)-C(27) fragment of the marine macrolide family of bryostatin antibiotics is presented. The approach commences from achiral starting materials and has as its crucial step the enzymatic resolution of a racemic mixture of soluble polymer-supported alcohols (syn-10 and syn-11). The immobilized lipase from Candida antarctica (Novozym 435) catalyzes the enantioselective acetylation of syn-10 (in 40% conversion and >99% ee), allowing isolation of the key intermediate (R)-14 in enantiomerically pure form following its cleavage from the poly(ethylene) glycol (PEG) scaffold. The PEG matrix is both compatible with the multipolymer enzymatic transformation and allows for rapid purification and facile NMR characterization of all intermediates throughout the synthesis.
López-Pelegrín
J A
JA
Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Wentworth
P
P
Sieber
F
F
Metz
W A
WA
Janda
K D
KD
D054713:Bryostatins; D002175:Candida / Q000201:enzymology; D002849:Chromatography, Gas; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D008049:Lipase / Q000737:chemistry*; D018942:Macrolides; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism
D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1; D008049:Lipase