Total synthesis of (-)-hapalindole G: A novel tin-mediated indole synthesis
Doctor of Philosophy
The first total synthesis of ($-$)-hapalindole G, a member of novel chlorine- and isonitrile-containing hapalindoles from the cultured cyanophyte Hapalosiphon fontinalis, is accomplished. Our 21-step synthesis of ($-$)-hapalindole G from ($-$)-carveol features a stereospecific introduction of chlorine next to a quaternary center via cleavage of the cyclopropane intermediate and facile elaboration of the indole moiety through a conjugate addition of lithium methyl methylthiomethyl sulfoxide to an enone followed by hydrolysis of the resultant adduct. The absolute configuration of ($-$)-hapalindole G has therefore been confirmed on the basis of the specific rotation of our synthetic sample. Also described herein is a novel tin-mediated radical indole synthesis by using o-isocyanostyrene derivatives as starting materials via 2-tri-n-butylstannyl-3-substituted indoles as intermediates. The 2-tri-n-butylstannyl-indoles were also subjected to the one-pot Stille coupling reaction and iodination. The iodoindoles were capable of further manipulation. Our efficient synthesis paves the way for a facile construction of a variety of 3- or 2,3-substituted indoles from readily accessible isonitriles.
Organic chemistry; Pharmaceutical chemistry