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%.
| Original language | English |
|---|---|
| Article number | ss-2015-z0119-op |
| Pages (from-to) | 3009-3012 |
| Number of pages | 4 |
| Journal | Synthesis-Stuttgart |
| Volume | 47 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - 26 May 2015 |
Keywords
- aspartyl proteases
- hydroxyethylene isostere
- inhibitors
- lactones
- peptides
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Vila-Real, H., Lima, M. R., Maycock, C., Iranzo, O., & Simplício, A. (2015). An Alternative Synthetic Route to (3 R,5 S,1′ S)-5-{1′-[(tert -Butyloxycarbonyl)amino]-3′-methylbutyl}-3-methyldihydrofuran-2(3 H)-one, a Precursor of a Leu-Ala Hydroxyethylene Isostere. Synthesis-Stuttgart, 47(19), 3009-3012. [ss-2015-z0119-op]. https://doi.org/10.1055/s-0034-1381036