Document Report Card

ID: ALA1132918

Journal: J Med Chem

Title: Synthesis and evaluation of tryprostatin B and demethoxyfumitremorgin C analogues.

Authors: Wang H, Usui T, Osada H, Ganesan A.

Abstract: Tryprostatin B and demethoxyfumitremorgin C are fungal inhibitors of mammalian cell cycle progression at the G(2)/M transition. N-Alkyl derivatives of the L-Trp-L-Pro diketopiperazine were prepared as analogues of tryprostatin B, and two of these were more active than the natural product. A second series of cis- and trans-tetrahydro-beta-carbolines annulated to a diketopiperazine were prepared as analogues of demethoxyfumitremorgin C. The nature of the alkyl substituent, as well as its cis or trans relationship in the tetrahydro-beta-carboline ring, was found to have a significant effect on cytotoxic activity. Small cis-alkyl substituents fall into the demethoxyfumitremorgin C family, whereas bulky benzyl trans compounds appear to act via a different mechanism of action.

CiteXplore: 10780915

DOI: 10.1021/jm9905662