摘要：

Reported is a systematic study of the "fitness" (in terms of kcat/Km) of a series of phosphonate mimics of glucose 6-phosphate (G6P) as unnatural substrates for G6P dehydrogenase from Leuconostoc mesenteroides. The four G6P analogues (9, 10, 15a, and 15b) differ only in the degree of fluorination at the "bridging" phosphonate carbon. All have been synthesized from benzyl 6-O-trifluoromethanesulfonyl-2,3,4-tri-O-benzyl β-d-glucopyranoside (6). The phosphonates with bridging CH2 (9) and CF2 (10) groups are cleanly obtained by direct displacements with the appropriate LiX2CP(O)(OEt)2 reagents (X = H, F) in 15 min at 78 °C. For the (α-monofluoro)alkylphosphonates (15a/b), homologation of 6 is achieved via lithiodithiane-mediated triflate displacement, followed by aldehyde unmasking [CaCO3, Hg(ClO4)2, H2O]. Addition of diethyl phosphite anion produces diastereomeric, (α-hydroxy)phosphonates 13a/b (1.4:1 ratio) which may be readily separated by chromatography. The stereochemistry of the minor diastereomer was ...

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