An Alternative Synthetic Route to (3R,5S,1′S)-5-{1′-[(tert-Butyl­oxycarbonyl)amino]-3′-methylbutyl}-3-methyldihydrofuran-2(3H)-one, a Precursor of a Leu-Ala Hydroxyethylene Isostere

Abstract

An improved synthetic route to (3R,5S,1′S)-5-{1′-[(tert-butyl­oxycarbonyl)amino]-3′-methylbutyl}-3-methyldihydrofuran-2(3H)-one, a lactone precursor of the Leu-Ala (2R,4S,5S) hydroxyethylene isostere found in many peptidomimetic aspartyl protease inhibitors of Alzheimer’s­ disease, is devised. Alkylation of N-Boc-leucinal with the lithium salt of benzyl propargyl ether instead of ethyl propiolate is the key toward a more reproducible and efficient route to obtain the title lactone from N-Boc-l-leucine in six steps, and an overall yield of 16%.

Key words

inhibitors - peptides - lactones - hydroxyethylene isostere - aspartyl proteases

• References

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