Glycosyltransferase inhibitors: Synthesis of D-threo-PDMP, L-threo- PDMP, and other brain glucosylceramide synthase inhibitors from D- or L- serine

Scott A. Mitchell, Bryan D. Oates, Hossein Razavi, Robin L Polt

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The synthesis of enantiomerically pure (1S,2S)-1-phenyl-2- decanoylamino-3-N-morpholino-1-propanol (L-threo-PDMP) (1a) from L-serine, and the enantiomer (LR,2R)-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-threo-PDMP] (1b) from D-serine is reported. Reductive alkylation of the fully protected O'Donnell's Schiff base (3b) derived from D-serine provided the β-amino alcohol 5b in high yield and excellent selectivity, which yielded optically pure 1b in high yield after six steps. Three other D- threo-PDMP analogues with various amine groups have been synthesized using the same methodology, including the more potent pyrrolidine compound D- threo-PDPP (1e). A key feature of the synthesis is the isolation of tosylate (8b), which allows for the divergent synthesis of many analogues from a common advanced intermediate. The synthesis is amenable to large-scale production of D-threo-PDMP, L-threo-PDMP, and similar compounds.

Original languageEnglish (US)
Pages (from-to)8837-8842
Number of pages6
JournalJournal of Organic Chemistry
Volume63
Issue number24
DOIs
StatePublished - Nov 27 1998

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ceramide glucosyltransferase
Glycosyltransferases
Serine
Brain
Amino Alcohols
1-Propanol
Morpholinos
Enantiomers
Schiff Bases
Alkylation
Amines
RV 538

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Glycosyltransferase inhibitors : Synthesis of D-threo-PDMP, L-threo- PDMP, and other brain glucosylceramide synthase inhibitors from D- or L- serine. / Mitchell, Scott A.; Oates, Bryan D.; Razavi, Hossein; Polt, Robin L.

In: Journal of Organic Chemistry, Vol. 63, No. 24, 27.11.1998, p. 8837-8842.

Research output: Contribution to journalArticle

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