A synthesis of C(16),C(18)-bis-epi-cytochalasin D via Reformatsky cyclization.
Triene 5 has been prepared by the E-selective olefination of aldehyde 12 with the ylide 11. Several alternative syntheses of 12 were evaluated, and the successful route involved conversion of 22 into the vinyl ether 23 by Petasis olefination, followed by Claisen rearrangement. Diels-Alder cycloaddition of 5 with 4 gave the adduct 6 in 77% yield, and Reformatsky cyclization under dilution conditions afforded 10 (67%). After conversion to enol silane 32, oxidation with dimethyldioxirane produced 34. Conversion to a key intermediate 38 using electrophilic selenenylation and selenoxide rearrangement, followed by enolate alkylation and deprotection, gave 43. The X-ray crystal structure of 43 was determined to prove the stereochemistry.
Vedejs
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Chemistry Department, University of Wisconsin, Madison, Wisconsin 53706, USA. edved@umich.edu
Duncan
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SM
D018360:Crystallography, X-Ray; D003500:Cyclization; D015638:Cytochalasin D / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D019384:Nucleic Acid Synthesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D019384:Nucleic Acid Synthesis Inhibitors; D015638:Cytochalasin D