Mixed Branched-Linear Type One-Pot Glycosylation: Synthesis of Hepta β-D-glucoside

Abstract

A mixed branched-linear type one-pot glycosylation (OPG), which formed three glycosidic linkages in a single reaction vessel, has been developed. Synthesis of protected hepta b-D-glucoside has been achieved in three steps from monosaccharide building blocks by the OPG.Key words: oligosaccharide synthesis, one-pot glycosylation (OPG), mixed branched-linear type OPG, orthogonal anomeric leaving groups, hepta b-D-glucosideIn recent years, significant improvements in strategies 3 for oligosaccharide synthesis have been made. For example one-pot glycosylation (OPG) has attracted considerable attention, 4-7 since a number of glycosidic linkages are formed in a single reaction vessel without purifying the synthesized intermediates. Most of the reported OPGs are based on "activating-deactivating protective groups strategy" 4,5 or "orthogonal 8 anomeric leaving groups strategy" 5-7 synthesizing linear type oligosaccharides. It is also important to develop the OPG to deal with branched ones, which can be observed in naturally occurring oligosaccharides. We have already succeeded in the one-pot two-step sequential glycosylation using two orthogonal anomeric leaving groups and their own activator reagents (e.g. BrAgOTf, F-BF 3 ·OEt 2 , SPh-NIS/TfOH) to provide not only linear oligosaccharide, 7a,b,d ( Figure 1, type I) but also branched one. 7c,d ( Figure 1, type II) However, our OPG is not suitable for the construction of more complex branched-linear structure. Herein we report a development of mixed branched-linear type OPG (Figure 1, type III) to form three glycosidic linkages in a single reaction vessel and its application to the synthesis of hepta b-Dglucoside 6 having two branched saccharide units.Our designed mixed branched-linear type of OPG would be started by the branched type OPG to give the trisaccharide having a leaving group Z, followed by the glycosylation of the final glycosyl acceptor 4 to provide a branched tetrasaccharide 5 (Scheme 1). Glycosyl bromide, fluoride and ethyl thioglycoside were examined for the first glycosyl donor 1 and the second 2. Phenyl thioglycoside would be suitable for the third glycosyl donor 3 because of high stability of phenyl-thio group toward the above glycosylation conditions. For the regioselective glycosylation, the phenyl thioglycosides should possess a primary alcohol at C-6 and a secondary alcohol at C-3 or C-4, in which the more reactive primary alcohol could be glycosylated with the first glycosyl donor 1. To suppress the first glycosylation toward less reactive hydroxyl group in 3, the hydroxyl groups of 1 were protected with ester (deactivating) groups. This highly convergent strategy allows the efficient construction of branched-linear structures and minimizes the number of manipulations.Mixed branched-linear type OPG is illustrated in Scheme 1 and Table 1. 9 The sequential activation of the leaving groups was conducted in the following orders: 1) -Br, -F to -SPh. 2) -Br, -SEt to -SPh. 3) -F, -SEt to -SPh. 4) -SEt, -F to -SPh. Chemoselective activation of Br, -F, -SEt ...

“One-Pot” Protection, Glycosylation, and Protection–Glycosylation Strategies of Carbohydrates

“…Takahashi and co-workers employed this strategy for the one-pot syntheses of the core 2 class glycosyl amino acid (Figure ), a branched trisaccharide, dibranched heptasaccharide with phytoalexin elicitor activity, , and a library of dimeric Lewis X derivatives . Recently, Zhang and co-workers reported a one-pot assembly of 3,6-branched hexaarabinogalactan using an imidate/thioglycoside pair in an orthogonal and regioselective glycosylation combination setting …”

Synthesis of Laminarin Fragments and Evaluation of a β-(1,3) Glucan Hexasaccaride-CRM197Conjugate as Vaccine Candidate againstCandida albicans

“…Numerous syntheses of β-(1, 3) and β-(1, 6) glucans have been reported, so the preparation of the four oligosaccharides was achieved by adaptations of literature methods [13][14][15][16][17][18] in a way that we used only the three monosaccharide building blocks 9, [19] 8, and 12. [20] As a key building block for the introduction of β-(1, 3) and β-(1, 6) linkages we synthesized from compound 7b the monosaccharide 8, possessing two free hydroxyls in the 4 and 6 positions, which allow regioselective glycosylation of the latter [21] and a levulinoyl ester to protect position 3.…”

One-Pot Glycosylation (OPG) for the Chemical Synthesis of Oligosaccharides

“…Employing this strategy, together with the previous linear OPG with orthogonal donors, Takahashi et al were able to build a library of 72 trisaccharides on a Quest 210 TM manual synthesizer [57]. The branched and linear type OPG were then combined in one pot for the synthesis of the heptaglucan of the phytoalexin elicitor [58]. A remarkable six-step OPG synthesis of this interesting glucan was achieved on the manual synthesizer (Scheme 31) [59].…”