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Total synthesis and biological evaluation of tubulysin U, tubulysin V, and their analogues.

ABSTRACT: A stereoselective total synthesis of the cytotoxic natural products tubulysin U, tubulysin V, and its unnatural epimer epi-tubulysin V, is reported. Simplified analogues containing N,N-dimethyl-D-alanine as a replacement for the N-terminal N-Me-pipecolinic acid residue of the tubulysins are also disclosed. Biological evaluation of these natural products and analogues provided key information with regard to structural and stereochemical requirements for antiproliferative activity and tubulin polymerization inhibition.

SUBMITTER: Balasubramanian R

PROVIDER: S-EPMC4183140 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Total synthesis and biological evaluation of tubulysin U, tubulysin V, and their analogues.

Balasubramanian Ranganathan R Raghavan Bhooma B Begaye Adrian A Sackett Dan L DL Fecik Robert A RA

Journal of medicinal chemistry 20090101 2

A stereoselective total synthesis of the cytotoxic natural products tubulysin U, tubulysin V, and its unnatural epimer epi-tubulysin V, is reported. Simplified analogues containing N,N-dimethyl-D-alanine as a replacement for the N-terminal N-Me-pipecolinic acid residue of the tubulysins are also disclosed. Biological evaluation of these natural products and analogues provided key information with regard to structural and stereochemical requirements for antiproliferative activity and tubulin poly ...[more]

PMID: 19102699

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