| Abstract
| - l-Ascorbic acid is a versatile radical scavenger widely distributed in aerobic organisms that playsa central role in the protection of cellular components against oxidative damage by free radicalsand oxidants. It also functions as a physiological reductant for key enzymatic transformations incatecholamine neurotransmitters, amidated peptide hormones, and collagen biosynthetic pathways.Simple derivatives of l-ascorbic acid have been shown to possess antioxidant, antitumor, andimmunostimulant activities. The antioxidant and redox properties of l-ascorbic acid are closelyassociated with the electron-rich 2,3-enediol moiety of the molecule, and therefore, selectivefunctionalization 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 producethe corresponding 3-O-alkylated products under mild basic conditions due to the high nucleophilicityof the C-3-OH. Based on the density functional theory (B3LYP) electron density calculations, wehave devised a novel and general method for the direct alkylation of the 2-OH group of ascorbicacid with complete regio- and chemoselectivity. We have also carried out a complete spectroscopicanalysis of two complementary series of 2-O-acetyl-3-O-alkyl- and 2-O-alkyl-3-O-acetylascorbic acidderivatives to define their spectroscopic characteristics and to resolve common inconsistencies inthe literature.
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