Preparation method of efficient antitumor active polypeptide Tubulysin M

Abstract

The invention provides a preparation method of an efficient antitumor active polypeptide Tubulysin M. The preparation method comprises the following steps: S1, providing a compound 2; and S2, preparing the active polypeptide Tubulysin M by taking the compound 2 as a key raw material. According to the preparation method disclosed by the invention, an innovative route is adopted, the total synthesisprocess of the active polypeptide Tubulysin M is optimized, the total yield is relatively high, and the stereoselectivity is good.

Description

technical field [0001] The present invention relates to the technical field of medicines, and more specifically, relates to a preparation method of a high-efficiency anti-tumor active polypeptide TubulysinM. Background technique [0002] The tetrapeptide compound Tubulysins was extracted from myxobacteria by Hofle et al. in 2000, but its crystal structure was not determined until 2004. Tubulysin A-Z is a family of compounds, see Table 1, and they all belong to natural products. [0003] [0004] Table 1 Structural formulas of Tubulysins family compounds [0005] [0006] [0007] The active peptide Tubulysin M is obtained by chemists through structural modification, that is, the sensitive acetal is replaced by a stable methyl group. The study found that the active peptide Tubulysin M showed strong cytotoxic activity against human cancer cells, IC 50 Values ​​are in the lower nanomolar range, see Table 2 (reference J.Am.Chem.Soc., 2016, 138(5):1698-1708). The act...

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Problems solved by technology

However, its synthesis is not ideal. So far, most of the synthetic routes reported in the literature on the chemical synthesis of active polypeptide Tubulysin M and its analogues are not perfect, and there is a lot of room for further exploration.

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