Issue 29, 2017

A practical approach to asymmetric synthesis of dolastatin 10

Abstract

Dolastatin 10, an antineoplastic agent for cancer chemotherapy, is a linear peptide possessing N,N-dimethyl Val-OH, L-valine, (3R,4S,5S)-dolaisoleucine, (2R,3R,4S)-dolaproine and (S)-dolaphenine. Our efficient synthesis includes the following three key features: (1) SmI2-induced cross-coupling was employed to couple aldehyde 11 with (S)-N-tert-butanesulfinyl imine 12 to generate the required stereocenters of Dap (7); (2) asymmetric addition of chiral N-sulfinyl imine 10 provided a straightforward approach to the synthesis of the protected Doe ((S,S)-8); (3) a practical method to the key subunit Val-Dil (24a) has been established as an alternative synthetic route for the synthesis of this challenging chemical structure.

Graphical abstract: A practical approach to asymmetric synthesis of dolastatin 10

Supplementary files

Article information

Article type
Paper
Submitted
08 Jun 2017
Accepted
29 Jun 2017
First published
29 Jun 2017

Org. Biomol. Chem., 2017,15, 6119-6131

A practical approach to asymmetric synthesis of dolastatin 10

W. Zhou, X. Nie, Y. Zhang, C. Si, Z. Zhou, X. Sun and B. Wei, Org. Biomol. Chem., 2017, 15, 6119 DOI: 10.1039/C7OB01395G

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