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Enantioselective Total Synthesis of Cannogenol-3-O-?-l-rhamnoside via Sequential Cu(II)-Catalyzed Michael Addition/Intramolecular Aldol Cyclization Reactions.

ABSTRACT: A concise and scalable enantioselective total synthesis of the natural cardenolides cannogenol and cannogenol-3-O-?-l-rhamnoside has been achieved in 18 linear steps. The synthesis features a Cu(II)-catalyzed enantioselective and diastereoselective Michael reaction/tandem aldol cyclization and a one-pot reduction/transposition, which resulted in a rapid (6 linear steps) assembly of a functionalized intermediate containing C19 oxygenation that could be elaborated to cardenolide cannogenol. In addition, a strategy for achieving regio- and stereoselective glycosylation at the C3 position of synthetic cannogenol was developed and applied to the preparation of cannogenol-3-O-?-l-rhamnoside.

SUBMITTER: Bhattarai B

PROVIDER: S-EPMC5768146 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Enantioselective Total Synthesis of Cannogenol-3-O-α-l-rhamnoside via Sequential Cu(II)-Catalyzed Michael Addition/Intramolecular Aldol Cyclization Reactions.

Bhattarai Bijay B Nagorny Pavel P

Organic letters 20171215 1

A concise and scalable enantioselective total synthesis of the natural cardenolides cannogenol and cannogenol-3-O-α-l-rhamnoside has been achieved in 18 linear steps. The synthesis features a Cu(II)-catalyzed enantioselective and diastereoselective Michael reaction/tandem aldol cyclization and a one-pot reduction/transposition, which resulted in a rapid (6 linear steps) assembly of a functionalized intermediate containing C19 oxygenation that could be elaborated to cardenolide cannogenol. In add ...[more]

PMID: 29244520

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