Final‐Stage Site‐Selective Acylation for the Total Syntheses of Multifidosides A–C

Abstract

The first total syntheses of multifidosides A-C have been achieved. The synthetic strategy is characterized by catalytic site-selective acylation of unprotected glycoside precursors in the final stage of the synthesis. High functional-group tolerance of the site-selective acylation, promoted by an organocatalyst, enabled the conventionally difficult molecular transformation in a predictable and reliable manner. An advantage of this strategy is to avoid the risks of undesired side reactions during the removal of the protecting groups at the final stage of the total synthesis.

Total Synthesis of Ellagitannins <i>via</i> Sequential Site-Selective Functionalization of Unprotected D-Glucose

“…The site-selective acylation promoted by catalyst 9 was especially effective when applied for β-glucosides. [21][22][23][24] Accordingly, application of this method to site-selective introduction of a galloyl group into β-glucoside 7a seemed reasonable and promising, and was examined with catalyst 9 and the analogies.…”

Organocatalytic Site-Selective Acylation of Avermectin B_2a, a Unique Endectocidal Drug

“…We previously proposed a possible mechanism for the highly selective monoacylation of polyol compounds, [18][19][20][21][22][23][24][25][26][27] involving hydrogen bonding between the amide oxygen of catalyst 6 and the relatively acidic hydroxy group of the substrate. We therefore suspected that the C-7-allylic alcohol may take a hydrogen bond with the amide group of catalyst 6.…”

“…catalyst 6, which was effective for the site-selective monoacylation of polyol compounds such as glycopyranoses, [18][19][20][21][22][23][24] linear diols, 25) tri-and tetra-substituted α,α′-alkenediols, 26,27) 2-aminopentane-1,5-diol derivatives, 28) and 10-deacetylbaccatin III. 29) The amide oxygen of catalyst 6 acted as a Brøn-sted base to allow hydrogen bonding with the relatively acidic hydroxy group of the substrate, thus inducing selective acylation of the adjacent hydroxy group.…”

Organocatalytic Site-Selective Acylation of 10-Deacetylbaccatin III

“…Under these backgrounds, we have developed a method for a non-enzymatic site-selective acylation of polyol compounds such as natural glycosides catalyzed by 4-dialkylaminopyridine-type nucleophilic organocatalyst 6 and the derivatives [5][6][7][8][9][10] ( Fig. 1).…”