Looking glass inhibitors: synthesis of a potent naringinase inhibitor l-DIM [1,4-dideoxy-1,4-imino-l-mannitol], the enantiomer of DIM [1,4-dideoxy-1,4-imino-d-mannitol] a potent α-d-mannosidase inhibitor

The synthesis of l-DIM [1,4-dideoxy-1,4-imino-l-mannitol] and of 1,4-imino-d-glycero-l-talo-heptitol from d-glycero-d-gulo-heptono-1,4-lactone depends on the use of pentan-3-one to form two five ring ketals as described by Burke, rather than the formation of one five ring and one six ring ketal formed with acetone. l-DIM, the enantiomer of the potent α-d-mannosidase inhibitor DIM [1,4-dideoxy-1,4-imino-d-mannitol] is a good inhibitor of naringinase (an α-l-rhamnosidase) with a Ki of 3.63 μM. 1,4-Imino-d-glycero-l-talo-heptitol is a moderate inhibitor of naringinase.

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2,3:6,7-Di-O-diethylidene-d-glycero-l-talo-heptono-1,4-lactoneC17H28O7Ee = 100%[α]D21=-28.4 (c 1.93, CHCl3)Source of chirality: d-glycero-d-gulono-1,4-lactone as starting material

2,3:5,6-Di-O-diethylidene-d-glycero-l-talo-heptono-1,4-lactoneC17H28O7Ee = 100%[α]D22=-62.6 (c 1.60, CHCl3)Source of chirality: d-glycero-d-gulono-1,4-lactone as starting material

5-O-tert-Butyldimethylsilyl-2,3:6,7-di-O-diethylidene-d-glycero-l-talo-heptono-1,4-lactoneC23H42O7SiEe = 100%[α]D21=-14.6 (c 2.5, CHCl3)Source of chirality: d-glycero-d-gulono-1,4-lactone as starting material

5-O-tert-Butyldimethylsilyl-2,3:6,7-di-O-diethylidene-d-glycero-l-talo-heptitolC23H46O7SiEe = 100%[α]D21=+24.1 (c 3.1, CHCl3)Source of chirality: d-glycero-d-gulono-1,4-lactone as starting material

5-O-tert-Butyldimethylsilyl-2,3:6,7-di-O-diethylidene-1,4-di-O-methanesulfonyl-d-glycero-l-talo-heptitolC25H50O11S2SiEe = 100%[α]D20=-44.2 (c 0.85, CHCl3)Source of chirality: d-glycero-d-gulono-1,4-lactone as starting material

N-Benzyl 5-O-tert-butyldimethylsilyl-1,4-dideoxy-2,3:6,7-di-O-diethylidene-1,4-imino-d-glycero-l-talo-heptitolC30H51NO5SiEe = 100%[α]D20=+20.4 (c 0.85, CHCl3)Source of chirality: d-glycero-d-gulono-1,4-lactone as starting material

N-Benzyl 5-O-tert-butyldimethylsilyl-1,4-dideoxy-2,3-O-diethylidene-1,4-imino-d-glycero-l-talo-heptitolC25H43NO5SiEe = 100%[α]D23=+35.1 (c 1.05, CHCl3)Source of chirality: d-glycero-d-gulono-1,4-lactone as starting material

N-Benzyl 1,4-dideoxy-1,4-imino-l-mannitolC13H19NO4Ee = 100%[α]D21=+37.7 (c 1.20, H2O)Source of chirality: d-glycero-d-gulono-1,4-lactone as starting material

l-DIM (1,4-dideoxy-1,4-imino-l-mannitol)C6H13NO4Ee = 100%[α]D21=+10.3 (c 1.20, H2O)Source of chirality: d-glycero-d-gulono-1,4-lactone as starting material

N-Benzyl 1,4-imino-d-glycero-l-talo-heptitolC14H21NO5Ee = 100%[α]D21=+12.7 (c 2.04, MeOH)Source of chirality: d-glycero-d-gulono-1,4-lactone as starting material

1,4-Imino-d-glycero-l-talo-heptitolC7H15NO5Ee = 100%[α]D23=+9.5 (c 1.70, H2O)Source of chirality: d-glycero-d-gulono-1,4-lactone as starting material