Total synthesis of tubulysin U and its C-4 epimer.

Abstract

The Tup fragments of tubulysins were synthesized with a tandem reaction as the key step, and unexpected diastereoselectivity was observed in the first Grignard addition stage. The coupling of the enolate of a thiazolyl ketone with chiral sulfinimines furnished the backbone of the Tuv fragment with over 100:1 d.r. and high yield. Thus, tubulysin U and C-4 epi-tubulysin U were prepared in a highly selective and efficient manner. The results of the MTT assay furthermore indicated that C-4 epi-tubulysin U maintained significant growth inhibition activities against several cancer cell lines.

• Authors: Xiu-dong Yang, Chang-ming Dong, Jian Chen, Ya-hui Ding, Qi Liu, Xiao-yan Ma, Quan Zhang, Yue Chen
• Journal: Chemistry, an Asian journal (Chem Asian J) Vol. 8 Issue 6 Pg. 1213-22 (Jun 2013) ISSN: 1861-471X [Electronic] Germany
• PMID: 23576385 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antineoplastic Agents
• Oligopeptides
• Pipecolic Acids
• tubulysin U

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chemistry Techniques, Synthetic (methods)
• Humans
• Molecular Structure
• Oligopeptides (chemical synthesis, chemistry, pharmacology)
• Pipecolic Acids (chemical synthesis, chemistry, pharmacology)
• Stereoisomerism