Shoji Akai

Stereoselective and Efficient Total Synthesis of Optically Active Tetrodotoxin from d-Glucose

A stereoselective and efficient total synthesis of optically active tetrodotoxin (TTX) is described. A polyfunctionalized key cyclitol compound containing branched-chains for the synthesis of TTX was prepared from D-glucose employing the Henry reaction (Nitro aldol reaction) as the key transformation. Stereoselective construction of the alpha-azido-aldehyde branched-chain was achieved via the key spiro alpha-chloroepoxide intermediate.

Enzymatic synthesis of Kdn oligosaccharides by a bacterial α-(2→6)-sialyltransferase

Abstract Synthesis of CMP-deaminoneuraminic acid (CMP-β- d -Kdn) and its enzymatic transfer reaction using bacterial α-(2→6)-sialyltransferase were examined. CMP-β- d -Kdn was prepared from methyl 4,5,7,8,9-penta- O -acetyl-3-deoxy- d - glycero -β- d - galacto -2-nonulopyranosonate ( 2 ) in 24% overall yield. Enzymatic synthesis of Kdn oligosaccharide with CMP-β- d -Kdn (10.2 μmol), methyl β- d -lactosaminide ( 7 , 8.1 μmol) and purified sialyltransferase (80 munits) afforded Kdn-α-(2→6)-Gal-β-(1→4)-GlcNAc-β-1-OMe in 77% yield.

Improved synthetic method for preparing spiro α-chloroepoxides

A new synthetic method via α-chloroolefine derivatives for preparing epimers of spiro α-chloroepoxides (2-chloro-oxyrane derivatives), which are useful key intermediates for the synthesis of branched-chain functionalized compounds, is developed as an alternative to previous methods requiring dichloromethyllithium.

Tetrabutylammonium nitrite - acetic anhydride system, tetrabutylammonium nitrite, tetrabutylammonium acetate, and cesium acetate - 18-crown-6 for efficient unmasking of alkyl N-phenylcarbamates

Abstract Novel unmasking procedures for alkyl N-phenylcarbamates are established by the use of a tetrabutylammonium nitrite (Bu4NNO2) - acetic anhydride system, Bu4NNO2, Bu4NOAc, and CsOAc - 18-crown-6 towards variously functionalized sugar derivatives.

Synthesis of the starfish ganglioside LLG-3 tetrasaccharide.

The first synthesis of the ganglioside LLG-3 tetrasaccharide, which has attractive biological activities as well as a unique structure, is described. A C8-methoxy decorated sialic acid building block was initially prepared and a glycolic acid moiety was then introduced by sialylation. Amide condensation between the sialyl glycolic acid and an amino group at C5 on the sialyllactoside unit afforded the fully protected LLG-3 tetrasaccharide. Finally, the desired tetrasaccharide part of LLG-3 was obtained after careful global deprotection. [structure: see text].

Sialylation using N-glycolylneuraminyl phosphite donors to synthesize Neu5Gc-containing glycans

Efficient sialylations using N-glycolylneuraminic acid (Neu5Gc) phosphite donors having an acetyl or benzyl group on the glycolyl moiety are described in the synthesis of Neu5Gc-containing glycans. Both phosphite donors 1 and 2 were readily coupled with primary and secondary acceptor alcohols in propionitrile at -78 degrees C to provide the desired glycosides with good alpha-selectivities.

SYNTHESIS OF NEW GLYCOPOLYMERS CONTAINING β-D-MANNOPYRANOSE, AND C-2-SUBSTITUTED β-D-MANNOPYRANOSE RESIDUES AS A NEW CLASS OF INHIBITOR

New styryl monomers containing β-D-mannopyranose, 2-acetamido-2-deoxy-β-D-mannopyranose, 2-deoxy-2-fluoro-β-D-mannopyranose, and 2-deoxy-β-D-arabino-hexopyranose on their side chains, were efficiently synthesized as a new class of a potent inhibitor resistant to exo-α-mannosidase digestion. The binding affinity of the carbohydrate polymers obtained from those mannopyranosyl styryl monomers by radical polymerization with Concanavalin A were evaluated. A binding assay indicated that the multivalency effect and the affinity enhancement attained by modification at the C-2 position of the β-D-mannopyranoside residue resulted in the β-D-mannopyranosyl polymer which has the same affinity as that of the α-D-mannopyranosyl polymer.

Selective Deprotection Method of N-Phenylcarbamoyl Group

We report an improved method for the selective deprotection of the N-phenylcarbamoyl group, which yields the corresponding alcohol without affecting other protecting groups. Deprotection was performed using di-tert-butyl dicarbonate and tetra-n-butylammonium nitrite (Boc2O and Bu4NNO2) in pyridine at room temperature. This method is also effective for deprotecting the fluorous N-phenylcarbamoyl group.

Chemoenzymatic synthesis of [3,9-13C]-labeled NeuAc and KDN

Abstract The chemoenzymatic synthesis of 13 C-labeled sialic acid (NeuAc) and 3-deoxy- d - glycero - d - galacto -2-nonulosonic acid (KDN) as useful molecular probes for studying the conformation of sialyl or KDN oligosaccharides attached to proteins was performed by using [6- 13 C]-ManNAc, [6- 13 C]-Man and [3- 13 C]-pyruvic acid sodium salt. In the synthesis of the compounds, 5,6-anhydro intermediates were found to easily provide not only 6- 13 C-labeled but also 5-, and 6-modified NeuAc and KDN analogs. Furthermore, it was demonstrated that identical results are obtained by NMR for both [3,9- 13 C]-NeuAc and 1:1 mixtures of [3- 13 C]- and [9- 13 C]-NeuAc.

Practical synthesis of [1-13C]- and [6-13C]-d-galactose

Abstract The chemical synthesis of 13 C-labeled d -galactose as useful molecular probes for studying the conformation of oligosaccharides attached to proteins was performed. The method for synthesizing the title labeled compounds was newly developed via the corresponding 1-ene and 5-ene compounds derived from 1,2:5,6-di- O -isoproppylidene-α- d -galactofuranose by considering the efficient introduction of the atom. All protons of galactose from H-1 to H-6 were observed by the HMQC–HOHAHA technique using 1:1 mixtures of methyl [1- 13 C]- and [6- 13 C]-β- d -galactopyranoside, which were prepared from the title compounds.