First total synthesis of trehalose containing tetrasaccharides from Mycobacterium smegmatis

Abstract

Total synthesis of three important trehalose containing tetrasaccharides isolated from Mycobacterium smegmatis is reported for the first time, using regioselective opening of benzylidene acetals and stereoselective glycosylations as key steps. The 1,2-cis stereoselectivity in the glycosylation reactions was achieved using anchimeric assistance from a remote participating group, steric effects and solvent participation. The synthetic strategy can also be utilized for the assembly of structurally related oligosaccharides from M. tuberculosis.

α-Selective Glucosylation Can Be Achieved with 6-O-para-Nitrobenzoyl Protection

“…13 C­{ 1 H} NMR (101 MHz, CDCl 3 ) δ C (ppm) 166.1 ( C O), 138.2, 138.0, 137.6, 133.3, 133.2 (C Ar ) 132.4, 129.8, 128.9, 128.6, 128.5, 128.5, 128.3, 128.2, 128.1, 128.0, 127.7 ( C H Ar ), 87.4 (C1), 86.8 (C3), 80.8 (C2), 77.6 (C4), 77.2 (C5), 76.1 ( C H 2 Ph), 75.5 ( C H 2 Ph), 75.3 ( C H 2 Ph), 63.6 (C6). NMR data are in accordance with the literature . HRMS (ES): calcd for C 40 H 38 O 6 SNH 4 + m / z 664.2727; found m / z 664.2737.…”

“…R f (EtOAc/MeOH 8:1) 0.68, [α] D 299K + 6.0 ( c 1.0, CHCl 3 , lit. + 4.4 ( c 0.67 CHCl 3 )), Mp (uncorr.) 113.7–114.9 °C.…”

N‐Trifluoromethylthiosaccharin/TMSOTf: A New Mild Promoter System for Thioglycoside Activation

“…In spite of the extremely low reactivity of phenyl thioglycoside under the present conditions, we felt that we could turn it into an advantage. Hence, phenyl thioglucosyl acceptor 24 was prepared and exposed, together with ethyl thiogalactoside 14 , to the above activation conditions; as expected, the orthogonal activation of ethylthio group in the presence of phenylthio group took place smoothly and gave rise to the disaccharide 35 in 73 % yield (Table , entry 11). Obviously, 35 could be used immediately as glycosyl donor for further glycosidation reactions if necessary.…”

Enzymatic Synthesis and Structural Characterization of Novel Trehalose-Based Oligosaccharides

“…The majority of the studies based on the synthesis of trehalose derivatives focused on the synthesis of disaccharides analogues, such as lactotrehalose or mannotrehalose, , or trisaccharides, as the structures named above; , however, no tetra- or pentasaccharides were investigated. Chaube et al were the first to synthesize tetrasaccharides trehalose-derivatives from Mycobacterium smegmatis obtaining galactosyl and glucosyl structures linked by α-(1→6) and β-(1→6) to trehalose moieties, respectively. Nevertheless, the process of synthesis was arduous and complex, using organic solvents.…”