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Synfacts 2013; 9(1): 0013
DOI: 10.1055/s-0032-1317721
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Maxipost

Contributor(s):
Philip Kocienski
Li J, Cai Y, Chen W, Liu X, Lin L, Feng X * Sichuan University, Chengdu, P. R. of China
Highly Enantioselective Fluorination of Unprotected 3-Substituted Oxindoles: One-Step Synthesis of BMS 204352 (Maxipost).

J. Org. Chem. 2012;
77: 9148-9155
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Publication History

Publication Date:
17 December 2012 (online)

 
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Key words

maxipost - asymmetric fluorination - scandium triflate - N-fluorobenzenesulfonimide

Significance

Maxipost is a post-stroke neuroprotective agent that acts by opening large conductance Ca2+-activated (maxi-K) potassium channels. Previous syntheses of maxipost by asymmetric fluorination of oxindoles required protection of the oxindole nitrogen as the N-Boc derivative. The route depicted features the direct asymmetric catalytic fluorination of the oxindole A using N-fluorobenzenesulfinimide (B) in the presence of 10 mol% of a chiral complex derived from scandium triflate and the amine oxide ligand C.


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Comment

Attempts to perform the maxipost synthesis on a 3.5 mmol scale resulted in decreased yield and enantioselectivity (53% yield, 86% ee) due to the low solubility of the substrate. By constrast, the asymmetric fluorinaton of ox­indole D on a 4.0 mmol scale gave E in 93% yield and 97% ee. The small selection of the 29 examples described, showed that yields and enantio­selectivities are generally high.


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