The Dolastatins 20. A Convenient Synthetic Route to Dolastatin 15

George Pettit; Timothy J. Thornton; Jeffrey T. Mullaney; Michael R. Boyd; Delbert L. Herald; Sheo Bux Singh; Erik J. Flahive

doi:10.1016/S0040-4020(01)89562-4

The Dolastatins 20. A Convenient Synthetic Route to Dolastatin 15

George Pettit, Timothy J. Thornton, Jeffrey T. Mullaney, Michael R. Boyd, Delbert L. Herald, Sheo Bux Singh, Erik J. Flahive

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

31 Scopus citations

Abstract

A segment synthetic strategy was utilized for obtaining the Dolabella auricularia (Indian Ocean sea hare) depsipeptide dolastatin 15. Reaction of protected (S)-Hiva-(S)-Phe 2c with isopropenyl chloroformate followed by Meldrum's ester, cyclization (2c → 3a) of the product in toluene and finally methylation afforded the key (S)-dolapyrrolidine (Dpy) derivative 3b. Condensation of tripeptide 8 with the three unit Dpy segment 5b followed by deprotection and coupling (diethyl phosphorocyanidate) led to dolastatin 15 in 11% overall yield. The powerful and selective activity of dolastatin 15 against the U.S. National Cancer Institute's panel of human cell lines has been summarized.

Original language	English (US)
Pages (from-to)	12097-12108
Number of pages	12
Journal	Tetrahedron
Volume	50
Issue number	42
DOIs	https://doi.org/10.1016/S0040-4020(01)89562-4
State	Published - 1994

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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title = "The Dolastatins 20. A Convenient Synthetic Route to Dolastatin 15",

abstract = "A segment synthetic strategy was utilized for obtaining the Dolabella auricularia (Indian Ocean sea hare) depsipeptide dolastatin 15. Reaction of protected (S)-Hiva-(S)-Phe 2c with isopropenyl chloroformate followed by Meldrum's ester, cyclization (2c → 3a) of the product in toluene and finally methylation afforded the key (S)-dolapyrrolidine (Dpy) derivative 3b. Condensation of tripeptide 8 with the three unit Dpy segment 5b followed by deprotection and coupling (diethyl phosphorocyanidate) led to dolastatin 15 in 11% overall yield. The powerful and selective activity of dolastatin 15 against the U.S. National Cancer Institute's panel of human cell lines has been summarized.",

author = "George Pettit and Thornton, {Timothy J.} and Mullaney, {Jeffrey T.} and Boyd, {Michael R.} and Herald, {Delbert L.} and Singh, {Sheo Bux} and Flahive, {Erik J.}",

note = "Funding Information: Very necessary financial assistance was provided by the Outstanding Investigator Grant CA44344-OlAl-05 awarded by the NCI, DHHS, the Arizona Disease Control Research Commission, Eleanor W. Libby, the Waddell Foundation (Donald Ware), Herbert K. and Diane Cummings (The Nathan Cummings Foundation, Inc.), the Eagles Art Ehrmann Cancer Fund, Polly Trautman, and Lotte Flugel. We also wish to thank Drs. D. D. Burkett, C. L. Herald, F. Hogan-Pierson and S. B. Singh for other assistance.",

year = "1994",

doi = "10.1016/S0040-4020(01)89562-4",

language = "English (US)",

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AU - Pettit, George

AU - Thornton, Timothy J.

AU - Mullaney, Jeffrey T.

AU - Boyd, Michael R.

AU - Herald, Delbert L.

AU - Singh, Sheo Bux

AU - Flahive, Erik J.

N1 - Funding Information: Very necessary financial assistance was provided by the Outstanding Investigator Grant CA44344-OlAl-05 awarded by the NCI, DHHS, the Arizona Disease Control Research Commission, Eleanor W. Libby, the Waddell Foundation (Donald Ware), Herbert K. and Diane Cummings (The Nathan Cummings Foundation, Inc.), the Eagles Art Ehrmann Cancer Fund, Polly Trautman, and Lotte Flugel. We also wish to thank Drs. D. D. Burkett, C. L. Herald, F. Hogan-Pierson and S. B. Singh for other assistance.

PY - 1994

Y1 - 1994

N2 - A segment synthetic strategy was utilized for obtaining the Dolabella auricularia (Indian Ocean sea hare) depsipeptide dolastatin 15. Reaction of protected (S)-Hiva-(S)-Phe 2c with isopropenyl chloroformate followed by Meldrum's ester, cyclization (2c → 3a) of the product in toluene and finally methylation afforded the key (S)-dolapyrrolidine (Dpy) derivative 3b. Condensation of tripeptide 8 with the three unit Dpy segment 5b followed by deprotection and coupling (diethyl phosphorocyanidate) led to dolastatin 15 in 11% overall yield. The powerful and selective activity of dolastatin 15 against the U.S. National Cancer Institute's panel of human cell lines has been summarized.

AB - A segment synthetic strategy was utilized for obtaining the Dolabella auricularia (Indian Ocean sea hare) depsipeptide dolastatin 15. Reaction of protected (S)-Hiva-(S)-Phe 2c with isopropenyl chloroformate followed by Meldrum's ester, cyclization (2c → 3a) of the product in toluene and finally methylation afforded the key (S)-dolapyrrolidine (Dpy) derivative 3b. Condensation of tripeptide 8 with the three unit Dpy segment 5b followed by deprotection and coupling (diethyl phosphorocyanidate) led to dolastatin 15 in 11% overall yield. The powerful and selective activity of dolastatin 15 against the U.S. National Cancer Institute's panel of human cell lines has been summarized.

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JO - Tetrahedron

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The Dolastatins 20. A Convenient Synthetic Route to Dolastatin 15

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