Maitotoxin (MTX, 1) is the largest (MW 3422) and most toxic natural product so far discovered; it was isolated from the dinoflagellate Gambierdiscus toxicus.1 It is involved in ciguatera fish poisoning, and induces cell death by activating a variety of Ca2+ channel in various cell types. The structure of MTX consists of 98 chiral centers, 32 cyclic ether rings, 21 methyl groups, and 2 sulfate groups (only the hydrophobic part of MTX are shown in Figure 1). The characteristic structure and bioactivity of MTX are interested by synthetic organic chemists, and so far several fragments of MTX have been synthesized by Nicolaou’s,2a-e Oishi’s,2f-h and our groups.2i-k We have already reported stereoselective syntheses of the WXYZA’-ring2k and the C’D’E’F’-ring2j having a side chain. In this paper, we accomplished 1) a convergent synthesis of the RSTUV-ring system 4 via coupling of RS-ring carboxylic acid 6 and V-ring alcohol 5, an intramolecular Barbier reaction3 of the resulting iodo ester 7 with n-BuLi, and insertion of Me group to hemithioacetal 12, 2) a linear synthesis of the UVWXYZ-ring system 3 through 6-endo cyclization of vinyl epoxide,7 and SmI2-mediated reductive cyclization of aldehyde and β-alkoxy acrylate4 or β-alkoxy sulfoxide,5 and unique methyl insertion reaction,8 and 3) a convergent synthesis of the ent-ZA’B’C’D’-ring system 2 via the Suzuki-Miyaura cross coupling reaction7 of (Z)-vinyl iodide 25 with alkylborane devived from 26, hemithioacetal B’-ring formation, and reduction of the resulting hemithioacetal.9
