Efficient Kg-Scale Synthesis of Thrombin Inhibitor CRC 220
Potent thrombin inhibitor 2 is prepared in 10 steps with 20percent overall yield from commercial 4 on a kg-scale by the convergent approach depicted in Schemes 1 and 2.The (R)-configuration of the 4-amidinophenylalanine piperidide moiety is controlled by asymmetric hydrogenation.A novel method, the hydrogenolysis of amidoximes 11 and 21, is employed to attain a particularly clean transformation of the cyano into the amidinium functionality.Despite of the amorphous nature of target compound 2, the approach is devoid of any chromatographic purification.
Stereocontrol in the reduction of 1,2-diimine with an oxazaborolidine catalyst. Highly stereoselective preparation of (R,R)-1,2-diphenylethylenediamine
Highly enantioselective reduction of 1,2-bis(p-methoxyphenylimino)-1,2-diphenylethane was conducted even with 0.5 mol% of new oxazaborolidine derived from L-threonine and a stoichiometric amount of BH3·THF to give 1,2-diphenylethylenediamine derivative in excellent enantiomeric purity. The subsequent deprotection of nitrogen atoms afforded (R,R)-1,2-diphenylethylenediamine in enantiomerically pure form.
Shimizu, Makoto,Kamei, Mie,Fujisawa, Tamotsu
p. 8607 - 8610
(2007/10/02)
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