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Dihydropyridine C ‐Glycoconjugates by Hantzsch Cyclocondensation. Synthesis of a C (6)‐Glycosylated Nifedipine Analogue
Author(s) -
Dondoni Alessandro,
Massi Alessandro,
Minghini Erik,
Bertolasi Valerio
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200210)85:10<3331::aid-hlca3331>3.0.co;2-x
Subject(s) - chemistry , stereocenter , diastereomer , stereochemistry , knoevenagel condensation , moiety , glycoconjugate , ring (chemistry) , aldehyde , organic chemistry , enantioselective synthesis , catalysis , biochemistry
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.