Short-step Total Syntheses of Glycosides from Unprotected Glucose

<p> Stereoselective glycosidation is a key step for the synthesis of natural glycosides. The commonly used methods for glycosidation employ properly protected and activated carbohydrates as glycosyl donors, which are prepared by multi-step laborious processes. On the other hand, a direct method for glycosidation of acidic nucleophiles with unprotected glucose under Mitsunobu condition has been reported by Shoda et al. While the reaction took place chemoselectively at the anomeric position, the stereoselectivity for glycosidation was not satisfactory (a/b= up to 1/3). We have recently developed highly stereoselective glycosidation of gallic acid derivative using unprotected glucose as a glycosyl donor. The choice of dioxane as a solvent and use of finely powdered glucose were the keys to the successful transformation. We report here the application of this direct glycosidation to the natural product syntheses. The representative examples include one-step syntheses of natural glycosides from unprotected glucose and the corresponding carboxylic acids (Table 1). A possible origin of the high b-selectivity was also become clear by the experimental investigation. This method was applied to short-step total synthesis of a natural glycoside, coriariin A (1), possessing antitumor and immunostimulative activities. Double glycosidation of diacid 6 with two equivalents of glucose took place in high stereoselectivity to give diglycoside 7 (scheme 2). Total synthesis of coriariin A was achieved by overall 8 steps from unprotected glucose, which is much shorter than that required for previously reported total synthesis (15 steps). Moreover, in combination of this glycosidation and our originally developed regioselective acylation by organocatalyst 13, we achieved 6-steps total synthesis of pterocarinin C (2) from unprotected glucose.</p>