Synthesis of the Spiroketal Fragment of (–)‐Ushikulide A

Abstract

The stereoselective synthesis of the spiroketal fragment of the immunosuppressant (–)‐ushikulide A is described. The salient feature of this synthesis is the construction of the spiroketal moiety by hydrolysis of a dialkylated tosylmethyl isocyanide derivative derived from alkylation of tosylmethyl isocyanide (TosMIC) with suitably substituted halohydrin derivatives. The key functionalized tetrahydropyran ring was constructed by using Prins cyclization of the α‐acetoxy ether.

Progress towards the Synthesis of (‐)‐Ushikulide A: Synthesis of C1‐C15 Aliphatic and C17‐C31 Spiroketal Fragments by an Aldol Approach

“…The first total synthesis and absolute stereochemistry assignment of (‐)‐ushikulide A was reported by Trost and co‐workers . Later, our group also reported the synthesis of the spiroketal fragment of (‐)‐ushikulide A via a Prins cyclization process . In continuation of the synthesis of complex natural products, herein we disclose an alternate aldol strategy for the synthesis of both the C1‐C15 linear (5) and C17‐C31 spiroketal fragments (6) of (‐)‐ushikulide A (Figure ).…”