title: Probing the influence of a 4,6-O-acetal on the reactivity of galactopyranosyl donors: verification of the disarming influence of the trans-gauche conformation of C5-C6 bonds.
abstract: The effect of a 4,6-O-alkylidene acetal on the rate of acid-catalyzed hydrolysis of methyl galactopyranosides and of spontaneous hydrolysis of 2,4-dinitrophenyl galactopyranosides has been studied through the synthesis and hydrolysis of analogs in which O6 is replaced by a methoxymethylene unit in which the methoxy group adopts either an equatorial or an axial position according to the configuration. Consistent with earlier studies under both acid-catalyzed and spontaneous hydrolysis conditions, the alkylidene acetal, or its 7-carba analog, retards hydrolysis with respect to comparable systems lacking the cyclic protecting group. The configuration at C6 in the 7-carba analogs does not influence the rate of acid-catalyzed hydrolysis but has a minor influence on the rate of spontaneous hydrolysis of the 2,4-dinitrophenyl galactosides, confirming earlier studies on the role played by the hydroxymethyl group conformation on glycoside reactivity. The benzylidene acetal is found to stabilize the α-anomer of galactopyranose derivatives relative to monocyclic analogs. Reasons for the α-selectivity of 4,6-O-benzylidene-protected galactopyranosyl donors bearing neighboring group-active protecting groups at O2 are discussed.
authors.affiliation: Department of Chemistry, Wayne State University , 5101 Cass Avenue, Detroit, Michigan 48202, United States.
authors.forename: Myriame
authors.initials: M
authors.lastname: Moumé-Pymbock
authors.forename: Takayuki
authors.initials: T
authors.lastname: Furukawa
authors.forename: Sujit
authors.initials: S
authors.lastname: Mondal
authors.forename: David
authors.initials: D
authors.lastname: Crich
mesh_terms: D000080:Acetals / Q000737:chemistry*; D005690:Galactose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D006868:Hydrolysis; D007700:Kinetics; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000080:Acetals; D005690:Galactose