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

Helder Vila-Real, Maria Rita Lima, Christopher Maycock, Olga Iranzo, Ana Simplício

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish
Article numberss-2015-z0119-op
Pages (from-to)3009-3012
Number of pages4
JournalSynthesis-Stuttgart
Volume47
Issue number19
DOIs
Publication statusPublished - 26 May 2015

Keywords

  • aspartyl proteases
  • hydroxyethylene isostere
  • inhibitors
  • lactones
  • peptides

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