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Stereocontrolled enantioselective total synthesis of the [2+2] quadrigemine alkaloids.

ABSTRACT: A unified strategy for enantioselective total synthesis of all stereoisomers of the 2+2 family of quadrigemine alkaloids is reported. In this approach, two enantioselective intramolecular Heck reactions are carried out at the same time on precursors fashioned in four steps from either meso- or (+)-chimonanthine to form the two critical quaternary carbons of the peripheral cyclotryptamine rings of these products. Useful levels of catalyst control are realized in either desymmetrizing a meso precursor or controlling diastereoselectivity in elaborating C2-symmetic intermediates. None of the synthetic quadrigemines are identical with alkaloids isolated previously and referred to as quadrigemines A and E. In addition, we report improvements in our previous total syntheses of (+)- or (-)-quadrigemine C that shortened the synthetic sequence to 10 steps and provided these products in 2.2% overall yield from tryptamine.

SUBMITTER: Canham SM

PROVIDER: S-EPMC4526107 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Stereocontrolled enantioselective total synthesis of the [2+2] quadrigemine alkaloids.

Canham Stephen M SM Hafensteiner Benjamin D BD Lebsack Alec D AD May-Dracka Tricia L TL Nam Sangkil S Stearns Brian A BA Overman Larry E LE

Tetrahedron 20150901 37

A unified strategy for enantioselective total synthesis of all stereoisomers of the 2+2 family of quadrigemine alkaloids is reported. In this approach, two enantioselective intramolecular Heck reactions are carried out at the same time on precursors fashioned in four steps from either <i>meso</i>- or (+)-chimonanthine to form the two critical quaternary carbons of the peripheral cyclotryptamine rings of these products. Useful levels of catalyst control are realized in either desymmetrizing a <i> ...[more]

PMID: 26257440

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