Synthesis of tedanolide and 13-deoxytedanolide. Assembly of a common C(1)-C(11) subtarget.
[formula: see text] In this Letter we describe a synthetic strategy and an efficient assembly of a common C(1)-C(11) subtarget, (-)-3, for (+)-tedanolide (1) and (+)-13-deoxytedanolide (2), architecturally complex marine macrolides displaying potent antitumor activity. Key elements of the synthesis include two iterations of the Evans aldol protocol to construct the C(1)-C(6) moiety and a stereocontrolled vinyl anion addition to generate the C(8,9) trisubstituted olefin incorporating stereogenicity at C(7). Alkylation with a model epoxide demonstrates that (-)-3 is a competent dithiane for further elaboration of the macrolide skeleton.
Smith
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Department of Chemistry, University of Pennsylvania, Philadelphia, USA. smithab@sas.upenn.edu
Lodise
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D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D007783:Lactones / Q000138:chemical synthesis; D018942:Macrolides / Q000138:chemical synthesis*
C409106:13-deoxytedanolide; D000903:Antibiotics, Antineoplastic; D007783:Lactones; D018942:Macrolides; C119775:tedanolide