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Identification of rapid access to polycyclic systems via a base-catalyzed cascade cyclization reaction and their biological evaluation.

ABSTRACT: A base-mediated cascade reaction between malonate esters and acrolein was developed to access complex polycyclic systems. This novel tandem reaction enables the simultaneous generation of up to seven new bonds and at least three new stereogenic centers. Mechanistic studies indicate a series of nucleophilic 1,4 and 1,6 Michael addition reactions occur, followed by an aldol condensation reaction, culminating in the formation of three fused rings. The compounds were characterized by NMR studies and the stereochemistry was confirmed by X-ray analysis. The ability to generate multigram quantities of such complex molecular scaffolds renders the method promising for medicinal chemistry campaigns. Herein, we also demonstrate that the lead compounds display promising anti-proliferative activities against human cancer cell models.

SUBMITTER: Ling T

PROVIDER: S-EPMC7329093 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Identification of rapid access to polycyclic systems via a base-catalyzed cascade cyclization reaction and their biological evaluation.

Ling Taotao T Hadi Victor V Bollinger John J Rivas Fatima F

Bioorganic chemistry 20200418

A base-mediated cascade reaction between malonate esters and acrolein was developed to access complex polycyclic systems. This novel tandem reaction enables the simultaneous generation of up to seven new bonds and at least three new stereogenic centers. Mechanistic studies indicate a series of nucleophilic 1,4 and 1,6 Michael addition reactions occur, followed by an aldol condensation reaction, culminating in the formation of three fused rings. The compounds were characterized by NMR studies and ...[more]

PMID: 32334195

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