Rational approach to selective and direct 2-O-alkylation of 5,6-O-isopropylidine-L-ascorbic acid.
l-Ascorbic acid is a versatile radical scavenger widely distributed in aerobic organisms that plays a central role in the protection of cellular components against oxidative damage by free radicals and oxidants. It also functions as a physiological reductant for key enzymatic transformations in catecholamine neurotransmitters, amidated peptide hormones, and collagen biosynthetic pathways. Simple derivatives of l-ascorbic acid have been shown to possess antioxidant, antitumor, and immunostimulant activities. The antioxidant and redox properties of l-ascorbic acid are closely associated with the electron-rich 2,3-enediol moiety of the molecule, and therefore, selective functionalization of the 2- and 3-OH groups is essential for the detailed structure-activity studies. Reactions of 5- and 6-OH-protected ascorbic acid with electrophilic reagents exclusively produce the corresponding 3-O-alkylated products under mild basic conditions due to the high nucleophilicity of the C-3-OH. Based on the density functional theory (B3LYP) electron density calculations, we have devised a novel and general method for the direct alkylation of the 2-OH group of ascorbic acid with complete regio- and chemoselectivity. We have also carried out a complete spectroscopic analysis of two complementary series of 2-O-acetyl-3-O-alkyl- and 2-O-alkyl-3-O-acetylascorbic acid derivatives to define their spectroscopic characteristics and to resolve common inconsistencies in the literature.
Department of Chemistry, Wichita State University, Wichita, Kansas 67260-0051, USA.
Ayodele O
AO
Olabisi
Kandatege
K
Wimalasena
D000475:Alkenes / Q000737:chemistry; D000478:Alkylation; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure
D000475:Alkenes; C013658:propylene; D001205:Ascorbic Acid