Synthesis of the WXYZA′ Domain of Maitotoxin

Abstract

A synthesis of the WXYZA′ domain (7) of the marine neurotoxin maitotoxin (1) is reported. The convergent synthetic strategy involves construction of key building blocks 11 and 12, their coupling, and the elaboration of the resulting ester (10) to the target molecule through a ring-closing metathesis and a hydroxy dithioketal cyclization as the key steps. For the construction of fragment 11, the Noyori reduction/Achmatowicz rearrangement and hydroxy epoxide opening technologies were applied (starting from furfuryl alcohol (13)), whereas for the synthesis of fragment 12, a carbohydrate-based approach was adopted (starting from 2-deoxy-D-ribose (14)). The synthesized WXYZA′ domain (7) of maitotoxin (1) exhibited the expected ¹³C NMR chemical shifts, supporting the originally assigned structure of the corresponding region of the natural product.