The disarming effect of the 4,6-acetal group on glycoside reactivity: torsional or electronic?
An evaluation of whether the well-known deactivating effect of a 4,6-acetal protection group on glycosyl transfer is caused by torsional or an electronic effect from fixation of the 6-OH in the tg conformation was made. Two conformationally locked probe molecules, 2,4-dinitrophenyl 4,8-anhydro-7-deoxy-2,3,6-tri-O-methyl-beta-D-glycero-D-gluco-octopyranoside (18R) and the L-glycero-D-gluco isomer (18S), were prepared, and their rate of hydrolysis was compared to that of the flexible 2,4-dinitrophenyl 2,3,4,6-tetra-O-methyl-beta-D-glucopyranoside (21) and the locked 2,4-dinitrophenyl 4,6-O-methylidene-2,3-di-O-methyl-beta-D-glucopyranoside (26). The rate of hydrolysis at pH 6.5 was 21 > 18R > 18S > 26, which showed that the deactivating effect of the 4,6-methylene group is partially torsional and partially electronic. A comparison of the rate of acidic hydrolysis of the corresponding methyl alpha-glycosides likewise showed that the probe molecules 17S and 17R hydrolyzed significantly slower than methyl tetra-O-methyl-glucoside 19, confirming a deactivating effect of locking the saccharide in the (4)C(1) conformation. The experiments showed that the hydroxymethyl rotamers deactivate the rate of glycoside hydrolysis in the order tg >> gt > gg.
Jensen
Henrik Helligsø
HH
Department of Chemistry, University of Aarhus, 8000 Aarhus C, Denmark.
Nordstrøm
Lars Ulrik
LU
Bols
Mikael
M
D000080:Acetals / Q000737:chemistry* / Q000378:metabolism; D002236:Carbohydrate Conformation; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006868:Hydrolysis; D007700:Kinetics; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism; D011714:Pyrans / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity; D013329:Structure-Activity Relationship; D014102:Torsion Abnormality
D000080:Acetals; D006027:Glycosides; D009844:Oligosaccharides; D011714:Pyrans