First total synthesis of tubulysin B.
The first total synthesis of tubulysin B is described. The aziridine route to tubuphenylalanine (Tup) of the tubulysin D/U-series could not be transferred to the synthesis of tubutyrosine (blue moiety). Therefore, tubutyrosine (Tut) was synthesized by a Wittig olefination/diastereoselective catalytic reduction sequence. Interestingly, the C-2 epimer of tubulysin B has a cytotoxic activity almost identical to the natural diastereomer.
Pando
Orlando
O
Leibniz Institute of Plant Biochemistry, Department of Bioorganic Chemistry, Weinberg 3, D-06120 Halle (Saale), Germany.
Dörner
Simon
S
Preusentanz
Rainer
R
Denkert
Annika
A
Porzel
Andrea
A
Richter
Wolfgang
W
Wessjohann
Ludger
L
D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009231:Myxococcales / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010875:Pipecolic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D009842:Oligopeptides; D010875:Pipecolic Acids; D050257:Tubulin Modulators; C546650:tubulysin B