Synthesis of the ABCDEFG Ring System of Maitotoxin
2010-05-19T00:00:00Z (GMT) by
Maitotoxin (<b>1</b>) continues to fascinate scientists not only because of its size and potent neurotoxicity but also due to its molecular architecture. To provide further support for its structure and facilitate fragment-based biological studies, we developed an efficient chemical synthesis of the ABCDEFG segment <b>3</b> of maitotoxin. <sup>13</sup>C NMR chemical shift comparisons of synthetic <b>3</b> with the corresponding values for the same carbons of maitotoxin revealed a close match, providing compelling evidence for the correctness of the originally assigned structure to this polycyclic system of the natural product. The synthetic strategy for the synthesis of <b>3</b> relied heavily on our previously developed furan-based technology involving sequential Noyori asymmetric reduction and Achmatowicz rearrangement for the construction of the required tetrahydropyran building blocks, and employed a <i>B</i>-alkyl Suzuki coupling and a Horner−Wadsworth−Emmons olefination to accomplish their assembly and elaboration to the final target molecule.