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Highly diastereoselective reaction of a chiral, non-racemic amide enolate with (S)-glycidyl tosylate. Synthesis of the orally active HIV-1 protease inhibitor L-735,524

✍ Scribed by David Askin; Kan K Eng; Kai Rossen; Robert M Purick; Kenneth M Wells; R.P Volante; Paul J Reider


Publisher
Elsevier Science
Year
1994
Tongue
French
Weight
305 KB
Volume
35
Category
Article
ISSN
0040-4039

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✦ Synopsis


Reaction of chiral amide e&ate L&I with (S)-iyci&l tosylate I1 qj?ordt the epoxide 3 in 72% yield with high diastereoselectivity. Epoxide 3 is converte % to the orally-active WV-I protease inhibitor L-735,524 in 71% isolated yield.

Hydroxyetbylene dipeptide isosteres which contain the 1S,2R-1-amino-2-hydroxy-indanamide (AHI) moiety can be potent inhibitors of HIV-1 protease. * A highly diastereoselective route to the 2(R)-aryl-4(S)-hydroxy AH1

isosteres was recently developed via alkylation of (N-Boc)-a-amino-epoxides with the n-BuLi generated enolate

Li-1 (Scheme I>.2