S. Mitchell, B. Oates, H. Razavi
Nov 3, 1998
Citations
0
Influential Citations
13
Citations
Journal
Journal of Organic Chemistry
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 (1R,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.