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.

N-Glycosidation of D-psicofuranosyl donor 1 with pyrimidine bases took place β-selectively in a β/α-ratio of 8:1 ~ 7:1. For S-glycosidation, 3,4-O-(3-pentylidene)-protected D-psicofuranosyl donor 15 was effective to increase β-selectivity up to 7:1. INTRODUCTIONRare sugars including L-glucose, L-ribose, D-allose, D-tagatose, and so on, attract many scientists by their unique properties. 1 D-Psicose is one of the D-hexuloses and is also categorized into rare sugar due to its rare occurrence in nature. D-Psicose and its analogs have shown a variety of biological activities regarding anti-oxidant, 2 inhibitors against α-glucosidase 3,4 and N-acetylglycosyltransferase, 5 and anti-tumor activities. 6 However, limited supply and expensive price restrict development of their use and research. In 1993, Izumori et al. have found the specific isomerase for the transformation of D-fructose to D-psicose. 7 After developing this finding, recent successful mass-production has provided large quantities of D-psicose commercially available. 8 Indeed, due to a specific property as a low-calorie sweetener, D-psicose attracts dietary patients 9a and healthy consumers in food market to date. 9b We have investigated O-glycosidation reactions of D-psicose 10,11 in which we reported the chemical synthesis of 1 from D-ribose, 10 and found an excellent β-selectivity of 1 as an efficient D-psicofuranosyl donor with wide-range of glycosyl acceptors, such as monosaccharide, aliphatic alcohol, phenol, ceramide, and so forth (Scheme 1). 11,12 In an extension of these studies, we report β-selective D-psicofuranosidation with pyrimidines and thiols, herein. This paper is dedicated to Professor Kiyoshi Tomioka on the occasion of his 70th birthday. HETEROCYCLES, Vol. 97, No. 2, 2018 729 4 (R = H) 1 ref. 3a 0 °C to rt Bu 2 SnO 5 (R = Bz) 730 HETEROCYCLES, Vol. 97, No. 2, 2018

(+)-5-Thiosucrose and (+)-5-thioisosucrose were stereoselectively synthesized among four possible anomeric isomers using 5-thio-d-glucose as an α-directing glycosyl acceptor.

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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.