Total synthesis of (+/-)-deoxypenostatin A. Approaches to the syntheses of penostatins A and B.
A short synthesis of (+/-)-deoxypenostatin A (28) has been carried out using the convergent coupling of dienal 11, epoxide 13, and methylenetriphenylphosphorane (17) to prepare trienol 19 in only two steps. The key step is the Yb(OTf)(3)-catalyzed intramolecular Diels-Alder reaction of hydrated trienyl glyoxylate 23, which gives lactone 24 stereoselectively. Elaboration of lactone 24 to enone 27 by an intramolecular Horner-Emmons Wittig reaction and epimerization completes the synthesis of 28. Modest yields of Diels-Alder adducts 45a and 46a could be prepared analogously from MEM ether 44c, but the sensitivity of several of the intermediates precluded the elaboration of 45a to penostatin A (1).
Snider
B B
BB
Department of Chemistry, Brandeis University, Waltham, Massachusetts 02454-9110, USA. snider@brandeis.edu
Liu
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D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010407:Penicillium / Q000737:chemistry*
D000970:Antineoplastic Agents; D001578:Benzopyrans; C418126:deoxypenostatin A; C418127:penostatin A; C418128:penostatin B