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Synthesis 2015; 47(19): 3009-3012
DOI: 10.1055/s-0034-1381036
DOI: 10.1055/s-0034-1381036
paper
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
Weitere Informationen
Publikationsverlauf
Received: 14. März 2015
Accepted after revision: 26. Mai 2015
Publikationsdatum:
21. Juli 2015 (online)
![](https://www.thieme-connect.de/media/synthesis/201519/lookinside/thumbnails/ss-2015-z0119-op_10-1055_s-0034-1381036-1.jpg)
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%.
Supporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1381036.
- Supporting Information
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