Stereocontrolled synthesis of α-d-allulofuranosides using α-selective d-fructofuranosidation reaction.

Stereocontrolled synthesis of rare sugar derivatives, namely α-d-allulofuranosides, was achieved using d-fructose, one of the most abundant carbohydrates in nature. The following are the key steps of the α-d-allulofuranosides' synthesis. (1) An α-selective glycosidation reaction of 1,3,4,6-tetra-O-benzoylated d-fructofuranosyl donor to obtain α-d-fructofuranosides with 98 %-75 % isolated yields. (2) A regioselective 1,4,6-tri-O-pivaloylation reaction of the tetraol of α-d-fructofuranosides with the C3-hydroxy group remaining intact. (3) The oxidation of the C3-hydroxy group followed by the stereoselective reduction of the C3-carbonyl group. Primary and secondary alcohols and sugars can be used as glycosyl acceptors and aglycones for the following pivaloylation and stereoinversion reactions to obtain α-d-allulofuranosides.

E-Selective Ring-Closing Metathesis in α-Helical Stapled Peptides Using Carbocyclic α,α-Disubstituted α-Amino Acids.

We present an E-selective ring-closing metathesis reaction in α-helical stapled peptides at positions i and i + 4. The use of two chiral carbocyclic α,α-disubstituted α-amino acids, (1S,3S)-Ac5c3OAll and (1R,3S)-Ac5c3OAll, provides a high E-selectivity of a ≤59:1 E:Z ratio, while mixtures with E:Z ratios of 2.1-0.5:1 were produced with standard acyclic (S)-(4-pentenyl)alanine amino acids. A stapled octapeptide composed of (1S,3S)- and (1R,3S)-Ac5c3OAll amino acids showed a right-handed α-helical crystal structure.

X-ray Crystallographic Structure of α-Helical Peptide Stabilized by Hydrocarbon Stapling at i,i + 1 Positions.

Hydrocarbon stapling is a useful tool for stabilizing the secondary structure of peptides. Among several methods, hydrocarbon stapling at i,i + 1 positions was not extensively studied, and their secondary structures are not clarified. In this study, we investigate i,i + 1 hydrocarbon stapling between cis-4-allyloxy-l-proline and various olefin-tethered amino acids. Depending on the ring size of the stapled side chains and structure of the olefin-tethered amino acids, E- or Z-selectivities were observed during the ring-closing metathesis reaction (E/Z was up to 8.5:1 for 17-14-membered rings and up to 1:20 for 13-membered rings). We performed X-ray crystallographic analysis of hydrocarbon stapled peptide at i,i + 1 positions. The X-ray crystallographic structure suggested that the i,i + 1 staple stabilizes the peptide secondary structure to the right-handed α-helix. These findings are especially important for short oligopeptides because the employed stapling method uses two minimal amino acid residues adjacent to each other.

Stereoselective synthesis of (+)-5-thiosucrose and (+)-5-thioisosucrose.

(+)-5-Thiosucrose 1, a novel isosteric sulfur analog of sucrose, was synthesized stereoselectively for the first time via indirect ß-d-fructofuranosidation involving selective ß-d-psicofuranosidation, followed by stereo-inversion of the secondary hydroxy group at the C-3 position on the furanose ring. Glycosidation of protected 5-thio-d-glucose with a d-psicofuranosyl donor provided ß-d-psicofuranosyl 5-thio-α-d-glucopyranoside and that with d-fructofuranosyl donor gave α-d-fructofuranosyl 5-thio-α-d-glucopyranoside. Two anomeric stereocenters of the glycosyl donor and acceptor were controlled correctly to provide a single disaccharide among four possible anomeric isomers in the glycosylation. Conversion of the resulting disaccharides afforded (+)-5-thiosucrose 1 and (+)-5-thioisosucrose 2 in excellent yields, respectively. Inhibitory activities of 1 and 2 against α-glucosidase in vitro were also examined.