Concise syntheses of enantiomerically pure protected 4-hydroxypyroglutamic acid and 4-hydroxyproline from a nitroso-cyclopentadiene cycloadduct

O-TBS-protected methyl trans-4-hydroxypyroglutamate and methyl trans-4-hydroxyproline ester were synthesized from nitroso-cyclopentadiene Diels–Alder cycloadducts. Enzymatic resolution of the key intermediate, 4-amino-cyclopent-2-enol, provides access to both l- and d-amino acids.

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4(S)-(tert-Butyl-dimethyl-silanyloxy)-5-oxo-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2(R)-methyl esterC17H32NO6Si[α]D20=-34.7 (c 1.0, CHCl3)Source of chirality: Enzymatic acylationAbsolute configuration: (2R,4S)

4(S)-(tert-Butyl-dimethyl-silanyloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2(R)-methyl esterC17H34NO5Si[α]D20=+39.2 (c 1.0, CHCl3)Source of chirality: Enzymatic acylationAbsolute configuration: (2R,4S)