Stereoselective synthesis of triterpene and steroid 2-deoxy-α-glycosides using iodonium dicollidine perchlorate

Abstract

2-Deoxy-ct-glycosides of oleonane type triterpene alcohols and deoxycholic acid were synthesized by glycosylation with glycal acetates in the presence of iodonium dicollidine perchlorate followed by deiodination and deprotection.Key words: triterpene alcohols, deoxycholic acid. glycal acetates, iodonium dicotlidine perchlorate, stereoselective g[ycosylation, 2-deoxy-ct-glycosides.Earlier we have performed a stereoselective synthesis of 2-deoxy-a-D-arabino-hexopyranosides of triter~ene alcohols of the oleonane series using D-gtycal triacetate as the gtycosyl donor and iodine-containing promoters --N-iodosuccinimide (NIS) l and iodonium dicollidine perchlorate (IDCP). z 2,6-Dideoxy-a-L-arabino-hexopyranoside of glycyrrhetic acid, which is an analog of natural triterpene glycoside, glycyrrhizic acid, have been synthesized by glycosylation of methyl ester of 1813-glycyrrbetic acid (GLA) (the major biologically active triterpenoid of the extract of licorice roots) with di-O-acetyl-L-rhamnal in the presence of NIS and IDCP. 3 The same promoters were successfully used for the synthesis of steroid 2-deoxy-a-glycosides and oligosaccharides. 4,5In a continuation of our studies we extended a number of biologically active triterpenes and steroid alcohols used and carried out giycosylation of methyl esters of 18a-(la), II-deoxo-(lb), and 18,19-dehydroglycyrrhetic acids (le) with di-O-acetyl-u-rhamnal (2) and acetylcholic acid methyl ester (ld) with tri-O-acetyI-t~-glucal (3) in the presence of IDCP.The triterpene 2,6-dideoxy-2-iodoglycosides (4a--c) and steroid 2-deoxy-2-iodoglycoside (4d), obtained in high yields, underwent deiodination in the presence of 10% Pd/C to give glycosides 5a--d. Mild deacetylation of glycosides 5a---d yielded the target triterpene 2,6-dideoxy-ct-L-arabino-hexopyranosides (6a--c) and 2-deoxy-e,-c)-arabino-hexopyranoside of deoxycholic acid (6d) (Scheme t).

Chemical Modification of Glycyrrhizic Acid As A Route to New Bioactive Compounds for Medicine

“…When IDCP was used as a promoter of glycosylation the yield of the intermediate 2-deoxy-2-iodohexopyranosides was increased by approximately 20% as compared to the NIS method [92][93][94]. 2,6-dideoxy-α-L-arabino-hexopyranosides of 18β-, 18α-GLA, and 11-desoxo--GLA (196,199) were synthesized using di-O-acetyl-L-rhamnal and IDCP [91,94].…”

“…Oleanane type 3-O-2-deoxy-α-glycosides (194)(195)(196) were synthesized firstly in our laboratory via stereoselective glycosylation of methyl esters of 18β-and 18α-GLA, 11-desoxo-GLA and 18,19-dehydro-GLA with glycals acetates in the presence of iodine-containing activators such as N-iodsuccinimide (NIS) [89][90][91] and iodonium dicollidine perchlorate (IDCP) [92][93][94] ii i + ROH i ii yielded 2-deoxy-α-D-arabino-and lyxo-hexopyranosides of 18β-, 18α-GLA, and 11-deoxo-GLA as modified analogs of the natural glycoside, GL (1) [89][90][91]. When IDCP was used as a promoter of glycosylation the yield of the intermediate 2-deoxy-2-iodohexopyranosides was increased by approximately 20% as compared to the NIS method [92][93][94]. 2,6-dideoxy-α-L-arabino-hexopyranosides of 18β-, 18α-GLA, and 11-desoxo--GLA (196,199) were synthesized using di-O-acetyl-L-rhamnal and IDCP [91,94].…”

Glycals in the Stereoselective Synthesis of Triterpene 2-Deoxy-α-l-Glycosides under Conditions of Acidic Catalysis

“…At the present time, the glycal approach is regarded as an extremely useful method to obtain O -, C -, and N -glycosides and, in particular, oligosaccharides. An important contribution to this area was made by new strategies suggested by Danishefsky et al , However, there have been relatively few instances of glycosylation of steroid alcohols. − Earlier, we have used two iodine-containing activators, N -iodosuccinimide (NIS) and di( sym -collidine)iodonium perchlorate (IDCP), for the synthesis of some 2-deoxy- analogues of glycyrrhizic acid, the major glycoside of the licorice root extract. − Although the formation of triterpene 2-deoxy-glycosides when NIS and IDCP are used occurs with α-stereospecificity, an additional stage for preparation of 2-deoxy-2-iodo-α-glycosides requires subsidiary reagents, so the yields obtained for the target glycosides are not satisfactory.…”

“…[10][11][12] Earlier, we have used two iodine-containing activators, N-iodosuccinimide (NIS) and di(sym-collidine)iodonium perchlorate (IDCP), for the synthesis of some 2-deoxy-analogues of glycyrrhizic acid, the major glycoside of the licorice root extract. [13][14][15][16][17] Although the formation of triterpene 2-deoxy-glycosides when NIS and IDCP are used occurs with R-stereospecificity, an additional stage for preparation of 2-deoxy-2-iodo-R-glycosides requires subsidiary reagents, so the yields obtained for the target glycosides are not satisfactory.…”