Looking glass inhibitors: both enantiomeric N-benzyl derivatives of 1,4-dideoxy-1,4-imino-d-lyxitol [a potent competitive inhibitor of α-d-galactosidase] and of 1,4-dideoxy-1,4-imino-l-lyxitol [a weak competitive inhibitor of α-d-galactosidase] inhibit na

Benzhydryl protection by diphenyldiazomethane of an alcohol in enantiomeric base-sensitive ribonolactones allows short efficient syntheses of 1,4-dideoxy-1,4-imino-d-lyxitol (DIL) and of 1,4-dideoxy-1,4-imino-l-lyxitol (LIL). DIL showed potent [Ki = 0.13 μM]—and LIL showed weak [Ki = 113 μM]—competitive inhibition of α-d-galactosidase. Both enantiomers N-benzyl-DIL [Ki = 64 μM] and N-benzyl-LIL [Ki = 13 μM] were moderate competitive inhibitors of naringinase, an α-l-rhamnosidase.

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5-O-Benzhydryl-2,3-O-isopropylidene-1,4-di-O-methanesulfonyl-d-ribitolC23H30O9S2Ee 100%[α]D23=-21.7 (c 1.0, CHCl3)Source of chirality: d-ribonolactone as starting material

5-O-Benzhydryl-N-benzyl-2,3-O-isopropylidene-1,4-dideoxy-1,4-imino-d-lyxitolC28H31NO3Ee 100%[α]D20=-65.6 (c 0.99, CHCl3)Source of chirality: l-ribonolactone as starting material

N-Benzyl-1,4-dideoxy-1,4-imino-l-lyxitolC12H17NO3Ee 100%[α]D22=+46.6 (c 1.0, H2O)Source of chirality: d-ribonolactone as starting material

1,4-Dideoxy-1,4-imino-l-lyxitol hydrochorideC5H11NO3·HClEe 100%[α]D24=-20.7 (c 0.60, H2O)Source of chirality: d-ribonolactone as starting material