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Kinetically controlled Fischer glycosidation was achieved under flow conditions. β-Hydroxy-substituted sulfonic acid functionalized silica (HO-SAS) was used as an acid catalyst. This reaction directly converted aldohexoses into kinetically favored furanosides to enable the practical synthesis of furanosides. After optimization of the reaction temperature and residence time, glucofuranosides, galactofuranosides, and mannofuranosides were synthesized in good yields.

The efficient Pd-catalyzed coupling of unstable bicyclic pyrimidines and pyrazoles under basic conditions was established for the first time. The reactions proceeded with excellent yields without hydrolysis using Pd2(dba)3, t BuXPhos, and K3PO4.

4-Chlorophenyl ether was utilized as a new protecting group for the hydroxy function. This group was readily introduced to a sugar hydroxy group by using diaryliodonium triflate. Regioselective introduction of this protecting group at the vicinal cis-diol was achieved by using a copper catalyst and diaryliodonium triflate. This protecting group is stable under the Lewis acidic conditions of glycosylation, but it can be readily removed by the initial conversion into the corresponding 4-methoxyphenyl ether with use of a Pd catalyst, followed by oxidation with ammonium cerium (IV) nitrate [(NH4)2Ce(NO3)6] (CAN).

We describe a simple chiral-pool synthesis of (–)-longamide B, (–)-longamide B methyl ester, and (–)-hanishin. The key feature of the total synthesis is the formation of a piperazinone from a 1,2-cyclic sulfamidate and methyl 2-pyrrolecarboxylate, which permits efficient construction of the pyrrolopiperazinone core scaffold.

Guanylation proceeded efficiently upon treatment of the various amines with cyanamide in the presence of catalytic amounts of scandium(III) triflate under mild conditions. The method did not require the guanylation reagents to be preactivated, and the reaction proceeded efficiently in water. The method, therefore, has practical utility for substrates that dissolve only in aqueous solutions, for example, peptides or pharmacologically important compounds.

An integrated microfluidic/batch system was applied to the chemical N-glycosylation by the asparagine amide group, a key glycosyl bond-formation reaction in the synthesis of N-glycopeptides. By applying the advantageous features of microfluidic conditions, that is, efficient mixing and rapid heat transfer, the GlcNTrocβAsn and the Fuca(1―6)GlcNTrocβAsn fragments were efficiently prepared.

Highly α-selective sialylation of sialic acid N-phenyltrifluoroacetimidate with galactose acceptors, up to 100:0 and 92% for a(2-6)-sialoglycoside, while 97:3 and 77% for a(2-3)-sialoglycoside linkage formations, has beenrealized by introducing the C-5 N-phthalyl group on the donor. The 'fixed dipole effect' of N-phthalyl group was proposed in order to explain the high reactivity and α-selectivity. The N-phthalyl group was removed by treatment with methylhydrazine acetate, of which Neuα-Gal units can be readily applicable to the synthesis of a variety of N-linked oligosaccharides.

Solid-phase synthesis of indol-2-ones (2-oxindoles) by means of aryl radical cyclization of resin-bound N-(2-bromo-phenyl)acrylamides using Bu 3 SnH is described. Among various solvents tested, DMF was found to be the bestchoice for the radical cyclization inducing a reagent concentration effect of the polymer support. The reaction proceeded smoothly under microwave irradiation to give the desired indol-2-ones within a very short reaction time in comparison to conventional thermal heating. In this reaction, various indol-2-ones were synthesized by using commercially available 2-bromoanilines and acryloyl chloride derivatives.

Two new alkyne-type linkers having alkynylmethyloxy moieties were elaborated for solid-phase synthesis of oligosaccharides. A propargyl glycoside-type linker between a sugar residue and a solid support was formed by the Sonogashira reaction of a propargyl glycoside with polymer-supported iodobenzene. A propargyl ester-type linker was also constructed by the same reaction of a 4-(proparygyloxycarbonyl)benzyl glycoside with the latter. Both linkers are stable against acids such as TFA but can be readily cleaved with this acid after conversion to the corresponding alkyne-cobalt complex by treatment with Co 2 (CO) 8 . The latter ester linker is generally advantageous in that mild cleavage liberates a product as its carboxybenzyl glycoside which is readily purified. The Sonogashira reaction was found to proceed only at spatially reactive sites on the solid support where the reagent accesses readily, so that the subsequent reactions including glycosylation on solid phase proceeded smoothly to result in high total yields of the desired oligosaccharides.

A new method is described for affinity purification of synthetic compounds based on molecular recognition between bis(2,6-diaminopyridine)amide of isophthalic acid and a barbituric acid derivative. The desired compounds possessing the barbituric acid derivative as a tag were readily isolated from the reaction mix- ture by the following procedure. After each reaction cycle, the reac- tion mixture was applied to the polystyrene column possessing bis(2,6-diaminopyridine)amide of isophthalic acid as an artificial receptor. The compound possessing the barbituric acid tag was se- lectively adsorbed on the column, whereas other impurities without the tag such as excess reagents and byproducts were washed off. Subsequent desorption with CH2Cl2-MeOH (1:1) afforded the de- sired compound with high purity. This new strategy was applied to the synthesis of a heterocycle, peptides, and oligosaccharides.

New efficient synthesis of lipid A, an immunostimulat- ing glycoconjugate of bacteria, was achieved for the construction of lipid A library by using synthesis based on affinity separation (SAS), where the compounds possessing a barbituric acid (BA)-tag are selectively and rapidly purified by interaction with an artificial receptor for BA. Glycosylation of a glycosyl acceptor possessing the BA-tag with a 4'-phosphorylated N-Troc glucosaminyl trichlo- roacetimidate gave the disaccharide 4'-phosphate, which was puri- fied by the affinity separation. Successive removal of protective groups and introduction of acyl groups were then effected and the synthetic intermediate at each step was purified by the affinity sep- aration. Cleavage of the tag and subsequent deprotection afforded Escherichia coli lipid A. SAS enabled the rapid preparation of lipid A, therefore, proved to be a promising method for synthesis of other complex glycoconjugates.