Probing the Influence of a 4,6-O-Acetal on the Reactivity of Galactopyranosyl Donors: Verification of the Disarming Influence of thetrans–gaucheConformation 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 C7 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.

Cation Clock Reactions for the Determination of Relative Reaction Kinetics in Glycosylation Reactions: Applications to Gluco- and Mannopyranosyl Sulfoxide and Trichloroacetimidate Type Donors

“…This observation is consistent with the strongly disarming nature of the 4,6- O -benzylidene acetal, 52,134–136 as compared to two benzyl ethers, which in turn is a function of the imposition of the trans - gauche conformation 137 of the C5-C6 bond in which the electron-withdrawing effect of the C5-O5 bond is maximized. 138–140 A caveat to this argument concerns the use of different clock reactions in Figures 1a and c (vide infra), however, we believe that the comparison is justified here in view of the similarity of the two oxocarbenium ions (Scheme 7, 34 , R = Bn and R-R = PhCH).…”

A propos of glycosyl cations and the mechanism of chemical glycosylation; the current state of the art

“…Consequently, such systems are more susceptible to changes in ring conformation than the acetals they model and therefore overestimate the torsional component of the benzylidene effect while underestimating the electronic component. 48 A series of Wong-type competition glycosylations with arabinofuranosyl thioglycosides revealed the β-directing 3,5- O -di( tert- butyl) silylene acetal introduced earlier by the Boons 50 and Crich 51 laboratories to be strongly disarming consistent with the approximate tg conformation it imposes on the C4-C5 bond. 52 …”

“…6). 48 Pedersen and coworkers found a bicyclic 6-carbamannosyl donor to exhibit β-selectivity approaching that displayed by the now classical 4,6- O -benzylidene protected mannosyl donors, prompting them to suggest that the benzylidene effect is mainly torsional in origin and that the electronic component was previously overestimated. 49 However, it was subsequently pointed out by Crich and coworkers that the replacement of an acetal oxygen in an alkylidene protected 4,6-diol by a methylene group, as in the Pedersen model, or even more so by a methoxymethylene group (Fig.…”

Temperature Dependence of Hydroxymethyl Group Rotamer Populations in Cellooligomers

“…Its conformation and dynamics affects hydrogen bond pattern in crystals and solution, 1,2,3 reactivity, 4,5,6 and aqueous solubility. 7,8 The three-dimensional structure of carbohydrates is also a key feature for biological carbohydrate recognition.…”