Regioselective synthesis and biological evaluation of spiro-sulfamidate glycosides from exo-glycals

We report the synthesis of spiro-sulfamidate glycosides from exo-glycals. This route is regioselective and furnishes an original class of spiro-hydantoin glycoside analogues. A biological evaluation of this family on a range of glycosidases shows that these compounds are weak but very selective inhibitors of α-glucosidase and amyloglucosidase.

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(5S,7R,8R,9S,10R)-8,9,10-Tribenzyloxy-7-benzyloxy)methyl-1-methoxycarbonyl-3,6-dioxa-2-thia-1-azaspiro[4.5]decan-2,2-dioxideC37H39NO10S[α]D20=-8 (c 0.1, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (1S,2R,3S,4R,5R)

(5S,7R,8R,9S,10R)-8,9,10-Tribenzyloxy-7-benzyloxymethyl-1-tertbutoxycarbonyl-3,6-dioxa-2-thia-1-azaspiro[4.5]decan-2,2-dioxideC40H45NO10S[α]D20=+30 (c 0.1, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (5S,7R,8R,9S,10R)

(5S,7R,8R,9S,10R)-8,9,10-Trihydroxy-7-hydroxymethyl-1-methoxycarbonyl-3,6-dioxa -2-thia-1-azaspiro[4.5]decan-2,2-dioxideC9H15NO10S[α]D20=+19 (c 0.1, MeOH)Source of chirality: d-glucoseAbsolute configuration: (5S,7R,8R,9S,10R)

(5S,7R,8R,9S,10R)-8,9,10-Tribenzyloxy-7-benzyloxymethyl-3,6-dioxa-2-thia-1-azaspiro[4.5]decan-2,2-dioxideC35H37NO8S[α]D20=-18 (c 0.1, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (5S,7R,8R,9S,10S)

(5S,7R,8R,9S,10S)-8,9,10-Tribenzyloxy-7-benzyloxymethyl-1-methoxycarbonyl-3,6-dioxa-2-thia-1-azaspiro[4.5]decan-2,2-dioxideC37H39NO10S[α]D20=+36 (c 0.1, CHCl3)Source of chirality: d-mannoseAbsolute configuration: (5S,7R,8R,9S,10S)

(5S,7R,8R,9S,10R)-8,9,10-Trihydroxy-7-hydroxymethyl-3,6-dioxa-2-thia-1-azaspiro[4.5]decan-2,2-dioxideC7H13NO8S[α]D20=+26 (c 0.1, MeOH)Source of chirality: d-glucoseAbsolute configuration: (5S,7R,8R,9S,10R)

(5R,7R,8R,9S,10S)-8,9,10-Tribenzyloxy-7-benzyloxymethyl-1-methoxycarbonyl-3,6-dioxa-2-thia-1-azaspiro[4.5]decan-2,2-dioxideC37H39NO10S[α]D20=+12 (c 0.1, CHCl3)Source of chirality: d-mannoseAbsolute configuration: (5R,7R,8R,9S,10S)

(5S,7R,8S,9S)-8,9-Dimethylmethylenedioxy-7-tert-butyldiphenylsilyloxymethyl-1-methoxycarbonyl-3,6-dioxa-2-thia-1-azaspiro[4.4]nonan-2,2-dioxideC27H35NO5SSi[α]D20=-28 (c 0.1, CHCl3)Source of chirality: d-riboseAbsolute configuration: (5S,7R,8S,9S)

(5R,7R,8S,9S)-8,9-Dimethylmethylenedioxy-7-tert-butyldiphenylsilyloxymethyl-1-methoxycarbonyl-3,6-dioxa-2-thia-1-azaspiro[4.4]nonan-2,2-dioxideC27H35NO5SSi[α]D20=-56 (c 0.1, CHCl3)Source of chirality: d-riboseAbsolute configuration: (5R,7R,8S,9S)

(5R,7R,8S,9R)-8,9-Dibenzyloxy-7-benzyloxymethyl-1-tertbutoxycarbonyl-3,6-dioxa-2-thia-1-azaspiro[4.4]nonan-2,2-dioxideC32H37NO9S[α]D20=+12 (c 0.1, CHCl3)Source of chirality: d-arabinoseAbsolute configuration: (5R,7R,8S,9R)

(5S,7R,8S,9R)-8,9-Dibenzyloxy-7-benzyloxymethyl-1-tertbutoxycarbonyl-3,6-dioxa-2-thia-1-azaspiro[4.4]nonan-2,2-dioxideC32H37NO9S[α]D20=+36 (c 0.1, CHCl3)Source of chirality: d-arabinoseAbsolute configuration: (5S,7R,8S,9R)