Stereoselective synthesis of anti-N-protected 3-amino-1,2-epoxides by nucleophilic addition to N-tert-butanesulfinyl imine of a glyceraldehyde synthon.
A di-O-TBS protected glyceraldehyde synthon was condensed with Ellman's reagent to form a bench-stable N-tert-butanesulfinyl imine 6, which served as a common intermediate for the stereoselective introduction of various R groups. The Ellman adducts were converted to useful multifunctional intermediates 18a-i in one pot. The alcohols 18a-i were efficiently elaborated to both known and novel anti-N-protected-3-amino-1,2-epoxides in two steps. Compound 2a is a key intermediate toward HIV protease inhibitors.
Harried
Scott S
SS
Department of Medicinal Chemistry, Amgen Inc., Thousand Oaks, California 91320-1799, USA. sharried@amgen.com
Croghan
Michael D
MD
Kaller
Matthew R
MR
Lopez
Patricia
P
Zhong
Wenge
W
Hungate
Randall
R
Reider
Paul J
PJ
D000596:Amino Acids / Q000737:chemistry; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D005985:Glyceraldehyde / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity; D013452:Sulfonium Compounds / Q000737:chemistry*
D000596:Amino Acids; D004852:Epoxy Compounds; C481933:N-tert-butanesulfinylimino ester; D013452:Sulfonium Compounds; D005985:Glyceraldehyde; D009584:Nitrogen