Side-chain conformation, ascorbic acid

The crystal structure of D-gulono-1,4-lactone (2) has been determined,42 and is closely approximated by formula 38. Interestingly, the conformation of the side chain in 38 differs from that in crystalline L-ascorbic acid,1 very probably because of different steric interactions between the 3- and 5-hydroxyl groups in 2 (that is, 38) and 6. Bridgman43 measured the compressibility of gulono-1,4-lactone crystals. 

In 1977 NMR spectroscopy was used to assign a conformation to the side-chain of L-ascorbic acid (I) in water (21). That report stimulated us to measure the 600-MHz NMR spectra of I and D-iso-ascorbic acid (in) and their 4- and 5-deutero derivatives. The 600-MHz NMR spectra were analyzed, and the vicinal coupling constants were used to predict preferred conformations. 

Much progress has been made in recent years in the chemistry of ascorbic acid. At least six new syntheses of L-ascorbic acid have been devised since 1971. One of those methods was used to prepare specifically labeled L-ascorbic acid to investigate its biosynthesis in plants. Proton magnetic resonance at 600.2 MHz has shown that the side chain of L-ascorbic acid and its sodium salt in aqueous solution adopt the same conformation as crystalline L-ascorbic acid. The conformation of crystalline sodium L-ascorbate, on the other hand, is different. 

The similarity between the preferred conformations of the side-chain in both crystal lattice and aqueous solution is probably a consequence of the lack of intramolecular hydrogen-bonding in both environments. Considerable intermolecular hydrogen-bonding occurs, of course, with neighbouring ascorbic acid molecules in the crystal and with water molecules in aqueous solution. 

Vitamin C (ascorbic acid) (108) is a substance of paramount importance. The structural features obtained with the MNDO method are in qualitative agreement with the x-ray data <92JST(256)271>. More specifically, the 5-membered ring is almost planar and the side chain is very flexible, possessing three local minima with low intermediate barriers. The molecule adopts one of these minima in the crystal. Conformational analysis of (108) has also been carried out in aqueous solution employing H and C NMR spectra and molecular mechanics (MM2) <86JST(142)387>. 

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