A carbohydrate approach for the formal total synthesis of (−)-aspergillide C

Abstract

SummaryAn enantioselective formal total synthesis of aspergillide C is accomplished using commercially available tri-O-acetyl-D-galactal employing a Ferrier-type C-glycosylation, utilizing a Trost hydrosilylation and protodesilylation as key reactions.

De Novo Asymmetric Approach to Aspergillide‐C: Synthesis of 4‐epi‐seco‐Aspergillide‐C

“…Because of a combination of structural uniqueness and biological activity of the aspergillides, the synthesis of aspergillides has attracted much attention in synthetic community. [2,3,4,5,6,7] Herein we disclose our efforts at the de novo asymmetric synthesis of a C-4 epimer of the seco-acid of aspergillide-C. The synthetic approach that we envisioned was one ultimately aimed at the synthesis of aspergilide-C (Scheme 1).…”

“…There have been three syntheses of aspergillide-A, [3,4] six syntheses of aspergillide-B [3,5] and five syntheses of aspergillide-C. [6] The effort we envision hues most closely to the synthesis accomplished by Srihari, [5a] where they prepared a protected seco-acid like 2 via a Lewis acid catalyzed alkylation of a pyranone (e. g., 4). More specifically, we were interested in the synthesis of pyranone 4, which could serve as a Pd-glycosyl donor in a C-glycosylation reaction with β-keto-sulfone 5 to form 3, a protected precursor to seco-acid of aspergillide-C. Key to this approach is the recognition that β-keto-sulfone 5 could function as a vinyl anion equivalent for Pd-π-allyl electrophiles.…”