Synthesis and biological activity evaluation of dolastatin 10 analogues with N-terminal modifications

Xin Wang; Suzhen Dong; Dengke Feng; Yazhou Chen; Mingliang Ma; Wenhao Hu

doi:10.1016/j.tet.2017.03.006

Synthesis and biological activity evaluation of dolastatin 10 analogues with N-terminal modifications

Xin Wang
, Suzhen Dong
, Dengke Feng
, Yazhou Chen
, Mingliang Ma
, Wenhao Hu^*

^*Corresponding author for this work

School of Life Sciences

East China Normal University

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

We have described the synthesis of the two complex units (2R,3R,4S)-dolaproine (Dap) and (3R,4S,5S)-dolaisoleuine (Dil) of dolastatin 10 from natural amino acids. The stereoselective syntheses of N-Boc-Dap (4a) and N-Boc-(2S)-iso-Dap (4b) were performed by employing crotylation of N-Boc-L-prolinal as a key step. Barbier-type allylation of N-Boc-L-isoleucinal provided a mild and convenient approach for the synthesis of N-Boc-Dil (5a) and N-Boc-(3S)-iso-Dil (5b). Ten dolastatin 10 analogues have been designed and synthesized with N-terminal modifications based on the known compound monomethylauristatin F (MMAF, 3). In comparison with MMAF (3), four of the compounds showed enhanced potency against HCT 116 human colon cancer cells in vitro.

Original language	English
Pages (from-to)	2255-2266
Number of pages	12
Journal	Tetrahedron
Volume	73
Issue number	16
DOIs	https://doi.org/10.1016/j.tet.2017.03.006
State	Published - 2017

Keywords

Auristatins
Dap and Dil
Dolastatin 10 analogues
N-Terminal modification
Stereoselective synthesis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.tet.2017.03.006

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@article{2ce7b933f34d4501b02d177ff77c6e2e,

title = "Synthesis and biological activity evaluation of dolastatin 10 analogues with N-terminal modifications",

abstract = "We have described the synthesis of the two complex units (2R,3R,4S)-dolaproine (Dap) and (3R,4S,5S)-dolaisoleuine (Dil) of dolastatin 10 from natural amino acids. The stereoselective syntheses of N-Boc-Dap (4a) and N-Boc-(2S)-iso-Dap (4b) were performed by employing crotylation of N-Boc-L-prolinal as a key step. Barbier-type allylation of N-Boc-L-isoleucinal provided a mild and convenient approach for the synthesis of N-Boc-Dil (5a) and N-Boc-(3S)-iso-Dil (5b). Ten dolastatin 10 analogues have been designed and synthesized with N-terminal modifications based on the known compound monomethylauristatin F (MMAF, 3). In comparison with MMAF (3), four of the compounds showed enhanced potency against HCT 116 human colon cancer cells in vitro.",

keywords = "Auristatins, Dap and Dil, Dolastatin 10 analogues, N-Terminal modification, Stereoselective synthesis",

author = "Xin Wang and Suzhen Dong and Dengke Feng and Yazhou Chen and Mingliang Ma and Wenhao Hu",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",

year = "2017",

doi = "10.1016/j.tet.2017.03.006",

language = "英语",

volume = "73",

pages = "2255--2266",

journal = "Tetrahedron",

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TY - JOUR

T1 - Synthesis and biological activity evaluation of dolastatin 10 analogues with N-terminal modifications

AU - Wang, Xin

AU - Dong, Suzhen

AU - Feng, Dengke

AU - Chen, Yazhou

AU - Ma, Mingliang

AU - Hu, Wenhao

PY - 2017

Y1 - 2017

N2 - We have described the synthesis of the two complex units (2R,3R,4S)-dolaproine (Dap) and (3R,4S,5S)-dolaisoleuine (Dil) of dolastatin 10 from natural amino acids. The stereoselective syntheses of N-Boc-Dap (4a) and N-Boc-(2S)-iso-Dap (4b) were performed by employing crotylation of N-Boc-L-prolinal as a key step. Barbier-type allylation of N-Boc-L-isoleucinal provided a mild and convenient approach for the synthesis of N-Boc-Dil (5a) and N-Boc-(3S)-iso-Dil (5b). Ten dolastatin 10 analogues have been designed and synthesized with N-terminal modifications based on the known compound monomethylauristatin F (MMAF, 3). In comparison with MMAF (3), four of the compounds showed enhanced potency against HCT 116 human colon cancer cells in vitro.

AB - We have described the synthesis of the two complex units (2R,3R,4S)-dolaproine (Dap) and (3R,4S,5S)-dolaisoleuine (Dil) of dolastatin 10 from natural amino acids. The stereoselective syntheses of N-Boc-Dap (4a) and N-Boc-(2S)-iso-Dap (4b) were performed by employing crotylation of N-Boc-L-prolinal as a key step. Barbier-type allylation of N-Boc-L-isoleucinal provided a mild and convenient approach for the synthesis of N-Boc-Dil (5a) and N-Boc-(3S)-iso-Dil (5b). Ten dolastatin 10 analogues have been designed and synthesized with N-terminal modifications based on the known compound monomethylauristatin F (MMAF, 3). In comparison with MMAF (3), four of the compounds showed enhanced potency against HCT 116 human colon cancer cells in vitro.

KW - Auristatins

KW - Dap and Dil

KW - Dolastatin 10 analogues

KW - N-Terminal modification

KW - Stereoselective synthesis

UR - https://www.scopus.com/pages/publications/85014785168

U2 - 10.1016/j.tet.2017.03.006

DO - 10.1016/j.tet.2017.03.006

M3 - 文章

AN - SCOPUS:85014785168

SN - 0040-4020

VL - 73

SP - 2255

EP - 2266

JO - Tetrahedron

JF - Tetrahedron

IS - 16

ER -

Synthesis and biological activity evaluation of dolastatin 10 analogues with N-terminal modifications

Abstract

Keywords

UN SDGs

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