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 ...
The reactions of 2-phenyl-1-methylenecyclopropane with RhCl(PPh3)3 for 16 h at 50 °C and at 0 °C gave RhCl(η4-CH2CPhCHCH2)(PPh3)2 (1) and (2) as respective isolated products. Heating of a benzene solution of 2 at 50 °C turned it into 1 in a low yield (<7%), while the reactions of 2-phenyl-1-methylenecyclopropane with RhCl(PPh3)3 and with 2 at the same temperature afforded 1 (10%) and 2-phenyl-1,3-butadiene (14%).
A u t o m a t e d P a r a l l e l S y n t h e s i s o f a P r o t e c t e d O l i g o s a c c h a r i d e L i b r a r yAbstract: An efficient synthesis of a protected dimeric Lewis X epitope by two sequential one-pot glycosylations is described. Combinatorial synthesis of the dimeric Lewis X epitope derivatives by the one-pot glycosylation was accomplished utilizing an automated synthesizer to provide 12-protected oligosaccharides.Oligosaccharides on cell surface play important roles in many biological processes. 3 Most biologically active oligosaccharides are rare, and are difficult to purify. Additionally, their structural diversity based upon stereo-and regioisomers makes it difficult to determine their structure in comparison with that of oligopeptides and oligonucleotides. Therefore, the chemical synthesis of such oligosaccharides would strongly assist one in the elucidation of their structure-activity relationships. Recent developments of the chemical synthesis of oligosaccharide involving automated solid-phase synthesis, allows the high speed synthesis of a single target oligosaccharide. 4,5 Furthermore, combinatorial chemistry enables one to synthesize oligosaccharide libraries containing tri-or tetrasaccharides. 6,7,8d However, preparation of biologically active and complex natural product-based oligosaccharide libraries is still difficult to accomplish.One-pot glycosylation, involving sequential activation of glycosyl donors in a single vessel, is effective not only for the high speed synthesis of a single target oligosaccharide, but also for the parallel synthesis of oligosaccharide libraries. 7c,8,9 We have investigated the one-pot glycosylation based on the chemoselective activation of glycosyl donors attached with different leaving groups with appropriate activators, 9 and have already reported a one-pot sixstep synthesis of a di-branched heptasaccharide composed of a b(1,6) linked pentasaccharide backbone using seven independent building blocks. 9f If the requisite manipulations in the one-pot glycosylation are adaptable to an automated synthesizer, it would be an attractive way to synthesize structurally complex oligosaccharides. Scheme 1 Strategy for the one-pot synthesis of dimeric Lewis X derivative 1.
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