The use of glycosylated reagents in Hantzsch-type cyclocondensation reactions leading to C-glycosylated dihydropyridines (DHPs) has been investigated. A three-component approach with an anomeric sugar aldehyde (galacto, manno, and ribo derivatives), a β-keto ester, and an aminocrotonate afforded C(4)-glycosylated DHPs in high yield (70-90%). A two-component cyclocondensation approach based on different glycosylated β-amino acrylates (sugar enamines) and an enone derived from the Knoevenagel condensation between benzaldehyde and ethyl acetoacetate was followed for the preparation of C(6)-glycosylated 4-phenyl-substituted DHPs in fair yields (60-70%). The latter compounds were obtained as mixtures of diastereoisomers owing to the asymmetric induction of the sugar moiety in the formation of the C(4)-stereogenic center of the DHP ring. The diastereomer excess of the major products varied from 30 to 60%. The structure of selected compounds was determined by X-ray crystallography and by chiroptical measurements. The two-component cyclocondensation method was also employed for the preparation of a C(6)-ribofuranosyl-containing analogue of the well-known hypotensive agent nifedipine.

Dihydropyridine C-glycoconjugates by Hantzsch cyclocondensation. Synthesis of a C(6)-glycosylated nifedipine analogue

DONDONI, Alessandro;MASSI, Alessandro;BERTOLASI, Valerio
2002

Abstract

The use of glycosylated reagents in Hantzsch-type cyclocondensation reactions leading to C-glycosylated dihydropyridines (DHPs) has been investigated. A three-component approach with an anomeric sugar aldehyde (galacto, manno, and ribo derivatives), a β-keto ester, and an aminocrotonate afforded C(4)-glycosylated DHPs in high yield (70-90%). A two-component cyclocondensation approach based on different glycosylated β-amino acrylates (sugar enamines) and an enone derived from the Knoevenagel condensation between benzaldehyde and ethyl acetoacetate was followed for the preparation of C(6)-glycosylated 4-phenyl-substituted DHPs in fair yields (60-70%). The latter compounds were obtained as mixtures of diastereoisomers owing to the asymmetric induction of the sugar moiety in the formation of the C(4)-stereogenic center of the DHP ring. The diastereomer excess of the major products varied from 30 to 60%. The structure of selected compounds was determined by X-ray crystallography and by chiroptical measurements. The two-component cyclocondensation method was also employed for the preparation of a C(6)-ribofuranosyl-containing analogue of the well-known hypotensive agent nifedipine.
2002
Dondoni, Alessandro; Massi, Alessandro; Minghini, E; Bertolasi, Valerio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1198142
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