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A unified approach to ent-atisane diterpenes and related alkaloids: synthesis of (-)-methyl atisenoate, (-)-isoatisine, and the hetidine skeleton.

ABSTRACT: A unified approach to ent-atisane diterpenes and related atisine and hetidine alkaloids has been developed from ent-kaurane (-)-steviol (1). The conversion of the ent-kaurane skeleton to the ent-atisane skeleton features a Mukaiyama peroxygenation with concomitant cleavage of the C13-C16 bond. Conversion to the atisine skeleton (9) features a C20-selective C-H activation using a Suárez modification of the Hofmann-Löffler-Freytag (HLF) reaction. A cascade sequence involving azomethine ylide isomerization followed by Mannich cyclization forms the C14-C20 bond in the hetidine skeleton (8). Finally, attempts to form the N-C6 bond of the hetisine skeleton (7) with a late-stage HLF reaction are discussed. The synthesis of these skeletons has enabled the completion of (-)-methyl atisenoate (3) and (-)-isoatisine (4).

SUBMITTER: Cherney EC

PROVIDER: S-EPMC4160278 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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A unified approach to ent-atisane diterpenes and related alkaloids: synthesis of (-)-methyl atisenoate, (-)-isoatisine, and the hetidine skeleton.

Cherney Emily C EC Lopchuk Justin M JM Green Jason C JC Baran Phil S PS

Journal of the American Chemical Society 20140829 36

A unified approach to ent-atisane diterpenes and related atisine and hetidine alkaloids has been developed from ent-kaurane (-)-steviol (1). The conversion of the ent-kaurane skeleton to the ent-atisane skeleton features a Mukaiyama peroxygenation with concomitant cleavage of the C13-C16 bond. Conversion to the atisine skeleton (9) features a C20-selective C-H activation using a Suárez modification of the Hofmann-Löffler-Freytag (HLF) reaction. A cascade sequence involving azomethine ylide isome ...[more]

PMID: 25159015

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