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Computational and Experimental Analysis on the Conformational Preferences of Anticancer Saponin OSW-1

Fukaya, Keisuke, Urabe, Daisuke, Hiraizumi, Masato, Noguchi, Keiichi, Matsumoto, Takashi, Sakurai, Kaori
Journal of organic chemistry 2019 v.85 no.2 pp. 339-344
X-ray diffraction, arabinose, chemical reactions, crystal structure, models, moieties, organic chemistry, organic compounds, saponins, spectral analysis
The conformational properties of anticancer saponin OSW-1 were investigated by X-ray crystallography and by an integrated approach combining a conformational search and the evaluation of the computed conformational distribution by comparing the experimental and simulated spectroscopic data. Our results suggested that OSW-1 adopts two preferred conformations in solution at an approximately 2:1 ratio, of which the crystal structure is consistent with the major conformation. In the solution models, the arabinose residue of OSW-1 appears to serve as a molecular hinge by flipping from the standard ⁴C₁ form in the major conformer to the unusual ¹C₄ form in the minor conformer. This results in different orientations of the biologically essential p-methoxybenzoyl group, thereby inducing a dramatic alteration of the three-dimensional shape and polarity of OSW-1.