Tomoo Nukada

Total synthesis of X hapten, III3 Fucα-nLc4 Cer

Abstract Total synthesis of O -β- d -galactopyranosyl-(1→4)- O -[α- l -fucopyranosyl-(1→3)]- O -(2-acetamido-2-deoxy-β- d - gucopyranosyl)-(1→3)- O -β- d -galactopyranosyl-(1→4)- O -β- d -glucopyranosyl-(1→1)-2- N -tetracosanoyl- (2 S ,3 R ,4 E )-sphingenine was achieved by use of the key glycosyl donors O -(2,3,4,6-tetra- O -acetyl-β- d -galactopyranosyl)-(1→4)- O -[2,3,4-tri- O -acetyl- α- l -fucopyranosyl)-(1→3)]- O -(2-acetamido-6- O -acetyl-2-deoxy-β- d -glucopyranosyl)-(1→3)- O - (2,4,6-tri-O -acetyl- β- d -galactopyranosyl)-(1→4)-2,3,6-tri- O -acetyl-α- d -glucopyranosyl trichloroacetimidate and fluoride, as well as key glycosyl acceptor 3- O -benzoyl-2- N -tetracosanoyl-(2 S ,3 R ,4 E )-sphingenine, in an unambiguous manner.

Synthesis of α-d-Manp-(1→3)-[β-d-GlcpNAc-(1→4)]-[α-d-Manp-(1→6)]-β-d-Manp-(1→4)-β-d-GlcpNAc- (1→4)-[α-l-Fucp-(1→6)]-d-GlcpNAc, a core glycoheptaose of a “bisected” complex-type glycan of glycoproteins☆

Abstract A synthesis of α- d -Man p -(1→3)-[β- d -Glc p NAc-(1→4)]-[α- d -Man p -(1→6)]-β- d -Man p -(1→4)-β- d - Glc p NAc-(1→4)-[α- l -Fuc p -(1→6)]- d -Glc p NAc was achieved by employing benzyl O -(3,4,6-tri- O -benzyl-2- deoxy-2-phthalimido-β- d -glucopyranosyl)-(1→4)- O -(2- O -benzyl-β- d -mannopyranosyl)-(1→4)- O -(3,6-di- O -benzyl-2-deoxy-2-phthalimido-β- d -glucopyranosyl)-(1→4)-3- O -benzyl-2-deoxy-6- O - p -methoxyphenyl- 2-phthalimido-β- d -glucopyranoside as a key glycosyl acceptor. Highly stereoselective mannosylation was performed by taking advantage of the 2- O -acetyl group in the mannosyl donors. The α- l -fucopyranosyl residue was also stereoselectively introduced by copper(II)-mediated activation of methyl 2,3,4-tri- O -benzyl-1-thio-β- l -fucopyranoside.

Can the stereochemical outcome of glycosylation reactions be controlled by the conformational preferences of the glycosyl donor

Previous static and dynamical density functional theory studies of the 2,6-di-O-acetyl-3,4-O-isopropylidene-D-galactopyranosyl cations and their methanol adducts has led to an hypothesis that these cations exist in two families of conformers characterized as (2)S(O) and B(2,5), respectively. These families differ by ring inversion, each with its own reactivity. New calculations on the 2,6-di-O-acetyl-3,4-di-O-methyl-D-galactopyranosyl cation confirmed these trends. Removing the isopropylidene group allows more flexibility, but two families of conformers can be discerned with the monocyclic oxocarbenium ions in the E(3) conformation and the bicyclic dioxolenium ions in the (4)H(5) conformation. Attack on the beta-face of these monocyclic cations is favored by hydrogen bonding and the anomeric effect. The experimentally observed high beta-stereoselectivity of mannopyranosyl donors and high alpha-stereoselectivity of glucopyranosyl donors with the 4,6-O-benzylidene protecting groups can be rationalized assuming that the trans-fused 1,3-dioxane ring allows population of only one family of conformers. The combination of hydrogen bonding and conformational changes of the pyranose ring in response to the C-5[bond]O-5[bond]C-1[bond]C-2 torsion angle changes are identified as key factors in stereoselectivity. Based on these observations a strategy to design face discriminated glycosyl donors that exist predominantly in only one family of conformers is proposed.

Quantitative description of six-membered ring conformations following the IUPAC conformational nomenclature

Abstract Although several methods of quantitative conformational characterization exist in the literature, all these methods use a spherical polar coordinate representation which is in contrast to the qualitative description based on the IUPAC nomenclature. To bridge this gap this paper introduces a method to characterize six-membered ring conformations as a linear combination of ideal basic conformations. The linear combination coefficients are derived by projection of the vector of torsion angles onto those of ideal basic conformations. As the IUPAC nomenclature uses subscripts and superscripts to indicate atoms below and above the reference plane, the linear combination coefficients combined with the IUPAC name provide an instant visual image of the conformation. The method introduced here is based on endocyclic dihedral angles and requires only three dihedral angles for a full characterization, which is often available by NMR measurements for rigid conformations. We provide a table of equations to determine the missing dihedral angles based on redundancy conditions. The relationship between linear combinations and spherical representation similar to the well-known Cremer–Pople parameters is presented. In deriving the spherical conformational parameters we solved an inconsistency of previous definitions for spherical representation, namely that none of previous definitions place the intermediate halfchair or twistboat conformations exactly halfway between the pole (chair) and the equator (boat and twistboat) of the sphere as expected based on intuitive stereochemistry. To make our method generally available we provide an interface on the Internet that carries out all calculations described in the paper and allows the user to visualize, rotate and manipulate the ring (http://www.nrc.ca/ibs/6ring.html). By simplifying both the concepts and the access to carry out the calculations more experimental chemists can benefit from the description of ring conformation.

Total synthesis of a undecasaccharide: A typical carbohydrate sequence for the complex type of glycan chains of a glycoprotein

Abstract A first total synthesis of undecasaccharide 1 of complex type of glycans of a glycoprotein was achieved in a stereo- and regiocontrolled way.

Synthesis of a glycopeptide carrying a N-linked core pentasaccharide.

A glycopeptide carrying a pentasaccharide core structure of asparagine-linked glycoproteins was synthesized. The synthesis of the carbohydrate part was performed starting from monosaccharide components in an unambiguous manner. The resultant pentaglycosyl azide was reduced into corresponding glycosyl amine and coupled with an aspartic acid derivative to furnish an Asn-linked oligosaccharide in a protected form. Subsequent coupling with a dipeptide, followed by deprotection gave the target compound.

Synthesis of a branched mannohexaoside, a part structure of a high-mannose-type glycan of a glycoprotein☆

Abstract The synthesis is described of a branched mannohexaoside derivative, propyl 6- O -[3,6-di- O -(2- O -α- d -mannopyranosyl-α- d -mannopyranosyl)-α- d -mannopyranosyl]-α- d -mannopyranoside, which corresponds to the non-reducing-end part-structure of a high-mannose-type glycan of a glycoprotein.

Synthesis of a heptasaccharide hapten related to a bi-antennary glycan chain of human chorionic gonadotropin of a choriocarcinoma patient. A convergent approach☆

Synthesis of the heptasaccharide hapten 8-methoxycarbonyloctyl O-beta-D-galactopyranosyl-(1----4)-O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-(1----2)-O-[beta-D-galactopyranosyl-(1----4)-O-(2-acetam ido-2- deoxy-beta-D-glucopyranosyl)-(1----4)]-O-alpha-D-mannopyranosyl-(1----3) -O- [alpha-D-mannopyranosyl-(1----6)]-beta-D-mannopyranoside is described, by use of the known, protected glycosyl acceptor 8-ethoxy-carbonyloctyl O-(2,3,4,6-tetra-O-benzyl-alpha-D-mannopyranosyl)-(1----6)-2,4-di-O-benz yl-beta - D-mannopyranoside, and the key glycopentaosyl donors O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1----4)-O-(2-acetami do-3,6- di-O-acetyl-2-deoxy-beta-D-glucopyranosyl)-(1----2)-O-[(2,3,4,6-tetra-O- acetyl-beta-D-galactopyranosyl)-(1----4)-O-(2-acetamido-3,6-di-O-acetyl- 2- deoxy-beta-D-glucopyranosyl)-(1----4)]-3,6-di-O-benzyl-alpha-D-mannopyra nosyl trichloroacetimidate (5) and the corresponding fluoride 7, which, in turn, were prepared in 5 steps from allyl 3,6-di-O-benzyl-alpha-D-mannopyranoside in 35 and 22% overall yields, respectively. In model experiments, the key glycosyl donors 5 and 7 were also treated with the simple glycosyl acceptor 8-ethoxycarbonyloctanol, to give 8-methoxycarbonyloctyl O-beta-D-galactopyranosyl-(1----4)-O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-(1----2)-O-[beta-D-galactopyranosyl-(1----4)-O-(2-acetam ido-2- deoxy-beta-D-glucopyranosyl)-(1----4)]-alpha (and beta)-D-mannopyranoside.

Synthesis and absolute configuration of hormone α1

An important biological event in phytopathogens of the genus Phytophthora is sexual reproduction, which is conducted by two mating types, A1 and A2. A factor known as hormone alpha1 is secreted by the A1 mating type and induces the formation of sexual spores (oospores) in the A2 mating type. Here we describe the asymmetric synthesis and assignment of the absolute configuration of hormone alpha1 by oospore-inducing assays of the synthesized isomers.

An approach to regioselective alkylation of alkyl β-d-galactopyranosides through (trialkylstannyl)ation

Abstract Regioselective preparation of methyl 3,6-di- O -benzyl-β- d -galactopyranoside, methyl 2,4-di- O -benzyl-β- d -galactopyranoside, and methyl 3,4-di- O -benzyl-β- d -galactopyranoside by the stannyl method is described.