Owen Priest - Total Synthesis of Michellamines A-C, Korupensamines A-D, and Ancistrobrevine B.

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      Publication Details (including relevant citation   information):

    Hoye, Thomas R.; Chen, Minzhang; Hoang, Bac; Mi, Liang; and Priest, Owen P. "Total Synthesis of Michellamines A-C, Korupensamines A-D, and Ancistrobrevine B."  J. Org. Chem. 1999,64, 7184-7201.

       

      Abstract:

    Efficient syntheses of the title compds. have been developed. Several strategies for prepn. of each of the naphthalene and tetrahydroisoquinoline (THIQ) portions were developed. Initial attempts to use benzyne plus furan cycloaddn. reactions were thwarted by the unfavorable sense of the regiochem. outcome. An interesting annulation reaction of benzynes derived from 2,4-dibromophenol derivs. formed the core of the shortest naphthalene synthesis. An alternative annulation initiated by the addn. of a benzylic sulfone anion to Me crotonate led to an efficient naphthol synthesis amenable to large scale. The THIQ synthesis of Bringmann was used initially and subsequently complemented by a route whose key step involved the opening of N-tosyl-2-methylethyleneimine by a 3,5-dimethoxyphenylcuprate reagent. The results from a variety of aryl cross-coupling reactions are described. Suzuki coupling of the boronic acid derived from the naphthalene moiety with a THIQ-iodide was the most generally effective method for forming the hindered biaryl bond. The korupensamines and ancistrobrevine B were then revealed by deprotection. The oxidative coupling of several 4-aryl-1-naphthols to indigoids (cross ring naphthoquinones) with silver oxide effected the crit. dimerization reaction needed to establish the michellamine skeleton. For the perbenzylated precursor, hydrogen over palladium on carbon both reductively bleached the indigoid and hydrogenolyzed the benzyl ethers and amines to release the free michellamines. The synthesis of several michellamine analogs, including ent-michellamines, is outlined. Results of anti-HIV assays are presented.

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