A novel total synthesis of antillatoxin

Abstract

In this thesis, the total synthesis of (4R,5R)-antillatoxin, one of the most ichthyotoxic metabolites isolated to date from cyanobacterium, Lyngbya majuscule, is presented. The synthesis proceeds from commercial available trimethylacetaldehyde and produce the molecule in an overall yield of 1.1% over 15 steps. During the course of this total synthesis, 3 new methodologies were developed: (1) Nickel(0)-promoted homoallylation. (2) Syn diastereo-selective indium-mediated allylation. (3) Asymmetric indium-mediated allylation.Furthermore, the total synthesis of antillatoxin includes the following special features: an oxidation-reduction sequence has been developed to convert the relative stereochemistry at C4,C5 from syn to anti; a kinetic resolution may be involved for the coupling of the left fragment and the right fragment to afford the desired enantioselective (4R,5R)-linear ester; macrolactamization furnished the (4R,5R)-antillatoxin. Especially noteworthy are the convergent nature of this synthetic strategy and the incorporation of all the necessary functionalities in the early stages of the synthesis.