Synthetic Studies on Soraphen A: Synthesis of the C1-C9 Hemiketal Segment

Soraphen A (1) isolated from myxobacterium Sorangium cellulosum exhibits potent antifungal activity against various pathogenic plant fungi.1 This polyketide has highly efficient inhibitory action on eukaryotic acetyl-coenzyme A carbox-ylases (ACCs), and specifically their biotin carboxylase (BC) domains of ACCs.1 ACCs have crucial roles in the metabolism of fatty acids and, therefore, are targets for drug development against obesity, diabetes, and other diseases.2 This natural product contains an unsaturated 18-membered lactone ring, an unsubstituted phenyl ring, and a hemiketal ring constituting its structural feature.1 There have been several synthetic studies reported in the literature.3 The first total synthesis of soraphen A was reported by Giese in 1995.3a,b We have reported our synthetic studies.3e-f We envisioned that it would be the synthesis of soraphe