Regioselectivity of alkylation of cyclomaltoheptaose (beta-cyclodextrin) and synthesis of its mono-2-O-methyl, -ethyl, -allyl, and -propyl derivatives.
Mono-2-O-methyl-, -2-O-ethyl-, and -2-O-allyl-cyclomaltoheptaose were prepared by alkylations of cyclomaltoheptaose in dilute aqueous alkali, and mono-2-O-propylcyclomaltoheptaose was obtained by hydrogenation of the allyl derivative. All the 2-O-alkyl derivatives were less soluble in water than was cyclomaltoheptaose. All formed inclusion complexes with toluene in aqueous solution, but only the methyl ether was less soluble in the water-toluene system than in water. The solubilities of the other ethers in water were enhanced by the addition of toluene. Partial methylation of cyclomaltoheptase with 13C-enriched dimethyl sulfate in dilute aqueous alkali yielded mixtures of products. The substitution patterns were analyzed by GLC-MS of the alditol acetates, prepared by hydrolysis, reduction, and acetylation, and by 13C NMR after complete permethylation with nonenriched reagent. The results showed that methylation at O-2 is a predominant but not an exclusive reaction; as expected, the regioselectivity decreases with increasing degree of methylation.
Jindrich
J
J
National Institutes of Health, NIA/GRC, Baltimore, MD 21224.
Pitha
J
J
Lindberg
B
B
Seffers
P
P
Harata
K
K
D000478:Alkylation; D003505:Cyclodextrins / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D047392:beta-Cyclodextrins; C031215:betadex