Activation of glycosyl trichloroacetimidates with perchloric acid on silica (HClO4–SiO2) provides enhanced α-selectivity

Abstract

Obtaining high stereoselectivity in glycosylation reactions is often challenging in the absence of neighboring group participation. In this study, we demonstrate that activation of glycosyl trichloroacetimidate donors with immobilized perchloric acid on silica (HClO4–SiO2) provides higher α-selectivity than trimethylsilyl triflate (TMSOTf) for reactions that do not involve neighboring group participation.

Chemical O‐Glycosylations: An Overview

“…This activation also allowed glycosylations with glycosides having various protecting‐group manipulations, giving excellent yields. In sync, Gildersleeve and co‐workers also used HClO 4 –silica for enhanced α ‐selectivity . The moisture stability and easy handling of the catalyst made it highly useful in performing glycosylations with glycosyl trichloroacetimidates.…”

Concise Synthesis of the Phosphoglycerylated Tetrasaccharide Repeating Unit of the Capsular Polysaccharide of Streptococcus pneumoniae Serotype 11 A

“…Removal of the PMP group from compound 7 using ceric ammonium nitrate (CAN) [33] gave disaccharide hemiacetal derivative which on treatment with trichloroacetonitrile in the presence of DBU [34] furnished trichloroacetimidate derivative (8) in 79% over three steps. Stereo-and regioselective [2 + 2] block 1,2-cis glycosylation between the disaccharide trichloroacetimidate donor (8) with disaccharide diol acceptor (2) in the presence of HClO 4 -SiO 2 [29] in Et 2 O-CH 2 Cl 2 furnished (1!3) linked tetrasaccharide derivative which on acetylation using acetic anhydride and pyridine gave compound 9 in 70% over all yield. NMR and mass spectral analysis of compound 9 unambiguously confirmed the formation of expected product [signals at 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 158.0 and 159.0 Hz confirmed the b-linkages in the anomeric centres of the monosaccharides A and B.…”

“…The 2‐aminoethyl group at the reducing end of the repeating unit could serve as a readily available amino functionality for its further derivatization required for conjugating with a protein or an aglycon. The key features of this synthetic strategy are (a) convergent stereoselective [2+2] glycosylation; (b) use of perchloric acid supported over silica gel (HClO 4 ‐SiO 2 ) as a solid acid, for the activation of thioglycoside and glycosyl trichloroacetimidate derivatives; (c) regioselective 3‐ O ‐glycosylation of the D‐galactose moiety; (d) 1,2‐ cis glycosylation of C‐3 and C‐4 positions of D‐galactose moiety with high yield; (e) use of a p ‐methoxyphenyl (PMP) glycoside as a temporary protecting group at the anomeric position and (f) incorporation of a glyceroyl moiety through a phosphate linkage using glyceroyl phosphonate derivative in satisfactory yield.…”

Convergent synthesis of the tetrasaccharide repeating unit of the O-antigen of Shigella boydii type 9

“…3,4,6-Tri- O -acetyl-2-azido-2-deoxy-α-D-glucopyranosyl trichloroacetimidate ( 3 ) [33] was allowed to couple stereoselectively with ethyl 2,4-di- O -benzyl-1-thio-α-L-rhamnopyranoside ( 4 ) [34] under Schmidt’s reaction conditions [35] using perchloric acid supported on silica (HClO 4 –SiO 2 ) [23–24] as glycosylation activator to give ethyl (3,4,6-tri- O -acetyl-2-azido-2-deoxy-α-D-glucopyranosyl)-(1→3)-2,4-di- O -benzyl-1-thio-α-L-rhamnopyranoside ( 6 ) in 81% yield. Stereoselective formation of compound 6 was confirmed from its spectral analysis (presence of signals at δ 5.35 (br s, H-1 C ), 4.95 (d, J = 3.6 Hz, H-1 D ) in the 1 H NMR and signals at δ 92.8 (C-1 D ), 81.0 (C-1 C ) in the 13 C NMR spectrum).…”

“…The convergent synthesis of the target tetrasaccharide 1 as its 4-methoxyphenyl glycoside has been achieved applying a number of recently developed elegant reaction methodologies. A number of notable features are present in the synthetic strategy, which are (a) convergent [2 + 2] block glycosylation; (b) application of recently developed environmentally benign reaction conditions for protecting group manipulations and glycosylations such as, (i) O -acetylation using sulfamic acid [ 20 ], (ii) regioselective ring opening of the benzylidene acetal using a combination of triethylsilane and iodine [ 21 ], (iii) direct one-pot conversion of O -acetyl group to O -benzyl group [ 22 ], (iv) activation of glycosyl trichloroacetimidate and thioglycoside donors by perchloric acid supported on silica (HClO 4 –SiO 2 ) [ 23 – 26 ], and late stage TEMPO mediated selective oxidation [ 27 – 29 ] of the primary hydroxy group to the carboxylic group under phase transfer conditions without affecting the secondary hydroxy groups; (c) use of 4-methoxyphenyl (PMP) group as anomeric protecting group [ 30 – 31 ], which can be easily removed under oxidative conditions for the preparation of glycoconjugate derivatives. The synthesis of the target tetrasaccharide 1 was achieved by the stereoselective coupling of a D-maltose derived disaccharide derivative 2 and a disaccharide thioglycoside derivative 7 followed by functional group manipulations of the resulting tetrasaccharide derivative 8 .…”