A practical synthesis of (3R,4R)-N-tert-butoxycarbonyl-4-hydroxymethylpyrrolidin-3-ol.
The title compound (+)-, required for production of transition state analogue inhibitors of enzymes involved in T-cell-dependent disorders, was synthesized in five steps. A 1,3-dipolar cycloaddition of the nitrone formed from formaldehyde and N-benzylhydroxylamine to diethyl maleate gave the racemic cis-isoxazolidine (+/-)-. Reduction of the N-O bond of this compound gave pyrrolidone (+/-)- in excellent yield. A very efficient enzymic resolution of this racemic product led to the title enantiomer (+)-. This route employs only one chromatographic purification.
Clinch
Keith
K
Carbohydrate Chemistry Team, Industrial Research Ltd, P.O. Box 31310, Lower Hutt, New Zealand.
Evans
Gary B
GB
Furneaux
Richard H
RH
Lenz
Dirk H
DH
Mason
Jennifer M
JM
Mee
Simon P H
SP
Tyler
Peter C
PC
Wilcox
Sarah J
SJ
D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry
C524129:N-tert-butoxycarbonyl-4-hydroxymethylpyrrolidin-3-ol; D011759:Pyrrolidines