Synthesis and conformational analysis of 2-(indol-3-yl)ethyl α- l-arabinopyranoside and its 2,3,4-tri- O-acetyl derivative

Abstract

2-(Indol-3-yl)ethyl α- l-arabinopyranoside ( 5) was prepared by Ko¨nigs-Knorr condensation of the aglycon alcohol with 2,3,4- O-acetyl-β- l-arabinopyranosyl bromide, followed by O-deacetylation. The structure of the per- O-acetylated derivative ( 3) was determined. The crystals of 3 are trigonal, space group P3 121 with a = 8.367(4)A˚, c = 53.34(2)A˚, and Z = 6. The conformational analysis is based on the results obtained from X-ray structure analysis ( 3), 1H{ 1H}NOE measurements ( 3), and such computational Chemistry methods as molecular mechanics and molecular dynamics simulations ( 5). The α- l-arabinopyranose ring is in a 4 C 1 chair. Theoretical conformational analysis has been focused on the most flexible part of the molecule defined by four torsion angles about bonds which connect the carbohydrate residue and the indole nucleus. The conformer observed in the solid state is one of several possible forms indicated by molecular mechanics and molecular dynamics. The most probable forms are identified. In all observed conformers, the molecule studied maintains the indole ring approximately perpendicular to the side chain, which may be one of the prerequisites for bioactivity.