Journal of Organic Chemistry p. 6287 - 6295 (1994)
Update date:2022-08-03
Topics:
Pettit, George R.
Singh, Sheo Bux
Herald, Delbert L.
Lloyd-Williams, Paul
Kantoci, Darko
et al.
A special challenge in accomplishing the total synthesis of dolastatin 10 (1) entailed deducing the absolute configuration of the new β-methoxy-γ-amino acid component dolaproine (2) as 2S,2'R,3'R and devising a stereoselective synthesis.Synthesis of this unusual (S)-proline-derived unit as its N-tert-butoxycarbonyl derivative (9b) and three stereoisomers (9a, 9c, 9d) has been summarized.The diastereoisomers were assembled by an aldol condensation between aldehyde 5, derived from (S)-proline, with chiral propionate 6, followed by methylation and cleavage of the chiral directing ester group by hydrogenolysis to afford methyl ethers 9a-d.The absolute stereochemistry of the diastereoisomers was determined by a combination of X-ray crystallographic analyses (of 9a and lactam 11b formed from isomer 7a) and high-field (400 MHz) NMR studies.By using each of these isomers in a series of dolastatin 10 syntheses the stereochemistry of the dolaproine (2) unit of natural (-)-dolastatin 10 (1) was shown to be 2S,2'R,3'R.
View MoreShanghai AoBo Bio-Pharmaceutical Technology Co., Ltd.
Contact:+86-21-51320130-801, 816
Address:Room 601, No. 1011, Halei Road, Zhangjiang High-Tech Park, Pudong, Shanghai
Shanghai Pengkai Chemical Co.,Ltd
Contact:+86-21-60526671
Address:No.4226 Duzhuang Rd Minhang District Shanghai China
Airsea(Taizhou) Pharmaceutical Limited(expird)
Contact:+86-576-88057622
Address:Dubei, Duqiao, Linhai, Taizhou, Zhejiang, China Zip: 317016
Suzhou Chiral Pharmaceuticals Co., Ltd.
Contact:86-0512-63197058
Address:Building A, No. 2358, Chang'an Road, Wujiang Science Park
Geen Chemical Technology Co., Ltd
Contact:86-769-21660847
Address:1408, Yingfeng Commercial Center, Nancheng District
Doi:10.1016/S0040-4020(01)80638-4
(1994)Doi:10.1248/cpb.42.1363
(1994)Doi:10.1021/jm00049a018
(1994)Doi:10.1039/c4ra08384a
(2014)Doi:10.1021/ja00091a082
(1994)Doi:10.1039/c4cc00853g
(2014)