Takashi Kayashita

Pseudostellarins D-F, new tyrosinase inhibitory cyclic peptides from Pseudostellaria heterophylla

Abstract New potent tyrosinase inhibitory cyclic peptides, pseudostellarins D - F, have been isolated from the roots of Pseudostellaria heterophylla and the structures were elucidated by extensive 2D NMR methods, chemical and enzymatic degradation and ESI tandem MS spectroscopic analysis.

DICHOTOMINS A -E, NEW CYCLIC PEPTIDES FROM STELLARIA DICHOTOMA L. VAR. LANCEOLATA BGE.

Abstract New cyclic penta or hexapeptides, dichotomins A - E [A: cyclo(-Gly-Thr-Phe-Leu-Tyr-Val-); B: cyclo(-Gly-Thr-Phe-Leu-Tyr-Thr-); C: cyclo(-Gly-Thr-Phe-Leu-Tyr-Ala-): D: cyclo(-Gly-Val-Gly-Phe-Tyr-[le-): E: cyclo(-Gly-Tyr-Ala-Phe-Ala-)] . have been isolated from the roots of Stellaria dichotoma L. var. lanceolata Bge. Their structures were elucidated on the basis of extensive 2D NMR, chemical degradation and X-ray crystallographic analysis.

Conformation of cyclic heptapeptides: solid and solution state conformation of yunnanin A ☆

Abstract The solid and solution state conformation of yunnamin A, a cyclic heptapeptide, cyclo(-Gly-Tyr-Gly-Pro-Phe-Pro-), isolated from the roots of Stellaria yunnanensis were studied. The X-ray diffraction studies showed that the crystal of yunnanin A [orthorhombic form from a ethanol-methanol mixture, a=11.754 (10), b=12.576 (7), c=30.731 (6) A, space group P2221 z=4] had three intramolecular hydrogen bonds forming one type II, one type II′ β-turns and a classical β-bulge unit with all trans amide bonds. The dominant solution conformation analyzed by NMR spectroscopy, Monte Carlo (MC) are restrained molecular dynamics (MD) calculations implemented in MacroModel/Batchmin (Ver. 4.5) was homologous to that in the solid state.

Crystal and solution forms of a cyclic heptapeptide, pseudostellarin D1)

Abstract Crystal and solution forms of a cyclic heptapeptide, pseudostellarin D, cyclo(Gly-Tyr-Gly-Pro-Leu-Ile-Leu), were examined by spectroscopic evidences. A single crystal X-ray analysis showed that a revised structure, pseudostellarin D possesses a type II β-turn between Leu 7 and Gly 1 , and a type I β-turn between Pro 4 and Leu 5 . One transannular 4→1 hydrogen bond between Ile 6 -NH and Gly 3 -CO and two bifurcated hydrogen bonds between Tyr 2 -NH and Ile 6 -CO, and Gly 3 -NH and IIe 6 -CO were observed, forming a classical β-bulge unit in the crystal. The dominant solution conformation analyzed by high field NMR employing vicinal coupling constant, temperature dependence of NH protons, and ROESY spectrum was, on the whole, homologous to that observed in the solid state.

CONFORMATIONAL ANALYSIS OF A TYROSINASE INHIBITORY CYCLIC PENTAPEPTIDE, PSEUDOSTELLARIN A,FROM PSEUDOSTELLARIA HETEROPHYLLA

Abstract Conformational studies of pseudostellarin A were performed by a combination of high field NMR and computational chemical evidences to elucidate a relationship between the structures and their tyrosinase inhibitory activities in a series of cyclic peptides, pseudostellarins, and to establish a pharmacophore model. The three-dimensional structure of pseudostellarin A was characterized by γ - and β- turn structures, fixed by trans-annular hydrogen bonds between Gly and Leu.

Dichotomin A, a new cyclic hexapeptide from Stellaria dichotoma L. var. lanceolata Bge

Abstract A new cyclic hexapeptide, dichotomin A, showing cell growth inhibitory activity, has been isolated from the roots of Stellaria dichotoma L. var. lanceolata Bge. and the structure and solid state conformation were elucidated by extensive 2D NMR, chemical degradation and X-ray analysis.

Stereoselective radical additions of γ-oxy-α,β-unsaturated ester derivatives; 1,2-asymmetric induction in acyclic and cyclisation systems

Examination was made of 1,2-asymmetric induction in the addition of alkyl radicals to γ-oxy-α,β-unsaturated ester derivatives 1 and 2 prepared from ethyl lactate and (R)-2,3-O-isopropylideneglyceraldehyde 3, respectively. The addition reactions of hexyl, cyclohexyl and 3-phenylpropyl radicals to (Z)-2 derived from aldehyde 3 gave β-addition products with syn-stereoselectivity (syn : anti= 8.6 : 1—syn only). The reactions of (E)-2 where non-stereoselective. Based on allylic strain, a transition-state model for the syn-stereoselectivity is proposed. 1,2-Asymmetric induction was carried out in radical cyclisation to synthesize active cyclohexane derivatives.