A facile and highly stereoselective synthesis of 1-thiotrehalose

One-Pot, Highly Stereoselective Synthesis of Dithioacetal-α,α-Diglycosides

“…The yield was further improved to 60% by adding 4Å molecular sieves [ 18 ] in the reaction mixture to avoid any possible inhibition of the thioacetalization reaction by traces of water in the reaction mixture (entry 4, Table 1 ). It was anticipated that the presence of water may facilitate the in situ hydrolysis of the glucosyl silyl sulfide intermediate B to the corresponding less reactive thiol ( Figure 1 ) [ 19 ]. The addition of more equivalents of benzaldehyde at −78 °C in the presence of 4Å molecular sieves led to a clean reaction mixture as judged on TLC.…”

An Expeditious Synthesis of 1-Thiotrehalose

“…It is noteworthy that the introduction of α,α-anomeric linkages with high stereocontrol is considered to be particularly challenging. [8][9][10][11][12][13][14][15] Deprotection of benzyl groups with hydrogen in the presence of palladium afforded 1-thiotrehalose (4) in 95% yield (Scheme 2). 20 Quite surprisingly, in the absence of EtOAc, the reaction did not proceed and compound 3 was recovered.…”

“…3,6 In particular, due to the higher resistance of its S-linked isostere to chemical and enzymatic hydrolysis, many efforts have been directed towards the synthesis of 1-thiotrehalose analogues. [8][9][10][11][12][13][14][15] Most methods involve the coupling of a thioglucoside with an activated sugar donor or a glycal. [8][9][10][11][12] For example, Zhu and Xin reported recently a four-step synthesis of a protected 1thiotrehalose derivative from 1,6-anhydro-D-glucose.…”

“…[8][9][10][11][12][13][14][15] Most methods involve the coupling of a thioglucoside with an activated sugar donor or a glycal. [8][9][10][11][12] For example, Zhu and Xin reported recently a four-step synthesis of a protected 1thiotrehalose derivative from 1,6-anhydro-D-glucose. 8 The key step was the diastereoselective glycosylation of an αglucosyl thiol acceptor 16 with a glucosyl trichloroacetamidate donor under typical Schmidt conditions.…”

“…[8][9][10][11][12] For example, Zhu and Xin reported recently a four-step synthesis of a protected 1thiotrehalose derivative from 1,6-anhydro-D-glucose. 8 The key step was the diastereoselective glycosylation of an αglucosyl thiol acceptor 16 with a glucosyl trichloroacetamidate donor under typical Schmidt conditions. In connection with our recent work on anhydrosugars, 17 we have designed a synthetic strategy in which the protected 1thiotrehalose 3 is obtained in one step from the commercially available tri-O-benzyl-1,6-anhydro-D-glucose (1) (Scheme 1).…”