A selective and mild glycosylation method of natural phenolic alcohols.

Mária Mastihubová,Monika Poláková

doi:10.3762/bjoc.12.51

Abstract

Several bioactive natural p-hydroxyphenylalkyl β-D-glucopyranosides, such as vanillyl β-D-glucopyranoside, salidroside and isoconiferin, and their glycosyl analogues were prepared by a simple reaction sequence. The highly efficient synthetic approach was achieved by utilizing acetylated glycosyl bromides as well as aromatic moieties and mild glycosylation promoters. The aglycones, p-O-acetylated arylalkyl alcohols, were prepared by the reduction of the corresponding acetylated aldehydes or acids. Various stereoselective 1,2-trans-O-glycosylation methods were studied, including the DDQ–iodine or ZnO–ZnCl2 catalyst combination. Among them, ZnO–iodine has been identified as a new glycosylation promoter and successfully applied to the stereoselective glycoside synthesis. The final products were obtained by conventional Zemplén deacetylation.

Highlights

Arylalkyl glycosides having a free phenolic function at the para-position of the aglycone are substances widely occurring in plants
The synthesis of the appropriate aglycones 6a–c was commenced from readily available commercial p-hydroxyphenylcarbaldehydes 4a–c which are less expensive than the corresponding p-hydroxybenzyl alcohols (Scheme 1)
The selection of methods C and D was based on the common knowledge that iodine, either alone or in combination with other promoters such as salts of various metals, serves as an effective activator of disarmed glycosyl halides in the 1,2-trans-glycoside synthesis [35,36,37,38]

Summary

Introduction

Arylalkyl (substituted benzyl, phenethyl and phenylpropenyl) glycosides having a free phenolic function at the para-position of the aglycone are substances widely occurring in plants. P-O-acetylated tyrosol (9) and p-O-acetylated coniferyl alcohol (12) were prepared from acids 7 and 10 by a two-step sequence: acid-catalysed acetylation of the phenolic hydroxy group (isolated yields >94%) followed by the reduction of the carboxylic function with NaBH4–I2 in THF (Scheme 2).

Results

Conclusion