Hirofumi Ohishi

Fumiquinazolines, novel metabolites of a fungus isolated from a saltfish

Abstract Fumiquinazolines A, B and C, exhibiting moderate cytotoxicity, were isolated from the mycelium of a strain of Aspergillus fumigatus which existed in the gastrointestinal tract of the saltwater fish Pseudolabrus japonicus . Their structures were elucidated by spectroscopic and X-ray diffraction analyses and chemical evidence.

Antineoplastic agents. 551. Isolation and structures of bauhiniastatins 1-4 from Bauhinia purpurea.

Bioassay-guided (P388 lymphocytic leukemia cell line) separation of extracts prepared from the leaves, stems, and pods of Bauhinia purpurea, and, in parallel, its roots, led to the isolation of four new dibenz[b,f]oxepins (2a, 3-5) named bauhiniastatins 1-4, as well as the known and related pacharin (1) as cancer cell growth inhibitors. The occurrence of oxepin derivatives in nature is quite rare. Bauhiniastatins 1-4 were found to exhibit significant growth inhibition against a minipanel of human cancer cell lines, and bauhiniastatin 1 (2a) was also found to inhibit the P388 cancer cell line. Structures for these new cancer cell growth inhibitors were established by spectroscopic techniques that included HRMS and 2D NMR.

Mode of binding of E-64-c, a potent thiol protease inhibitor, to papain as determined by X-ray crystal analysis of the complex

The three‐dimensional structure of the E‐64‐c‐papain complex has been determined by X‐ray crystal analysis at 2.5 Å resolution (conventional R = 26.9%). The structure determined indicates that: (i) the C2 atom of the oxirane ring of E‐64‐c is covalently bound by the Sγ atom of Cys‐25 of papain; (ii) this covalent bond formation results in a configurational conversion of the oxirane C2 atom from the S‐ to the R‐form; and (iii) extensive hydrogen bonding and hydrophobic interactions are responsible for the specific interaction of the E‐64‐c molecule with papain.

STANDISHINAL, A NOVEL CARBON SKELETAL DITERPENE FROM THE BARK OF THUJA STANDISHII (GORD.) CARR.

Standishinal ( 1 ), a new irregular abietane-type diterpenoid, was isolated from the bark of Thuja standishii and the absolute stereostructure was established by 2D NMR and X-ray crystallographic analyses. It was found that treatment of 12-hydroxy-6,7- seco -abieta-8,11,13-triene-6,7-dial ( 2 ) with BF 3 ·OEt 2 at 0°C in CH 2 Cl 2 furnished compound 1 .

A Novel Laccase Inhibitor, N-Hydroxyglycine, Produced by Penicillium citrinum YH-31

A Novel Laccase Inhibitor, N-Hydroxyglycine, Produced by Penicillium citrinum YH-31 Sawao Murao, Yuji Hinode, Eiko Matsumura, Atushi Numata, Kenzo Kawai, Hirofumi Ohishi, Hisanori Jin, Hiroshi Oyama & Takashi Shin a Department of Applied Microbial Technology, The Kumamoto Institute of Technology, Ikeda 4–22–1, Kumamoto 860, Japan b Osaka University of Pharmaceutical Sciences, Matsubara, Osaka 580, Japan Published online: 12 Jun 2014.

STEREOSELECTIVE SYNTHESIS OF THE C-4 LINKED IMIDAZOLE NUCLEOSIDES USING MODIFIED MITSUNOBU REACTION

Abstract A highly stereoselective synthesis of the novel 4-(β-D-ribofuranosyl)imidazole 5 was accomplished in 4 steps and 85% overall yield from protected D-ribose 1. Cyclization of the diol (RS)-3 having an intact imidazole by modified Mitsunobu reaction exclusively afforded benzylated β-ribofuranosylimidazole β-4a, accompanied by α-4a, in a ratio of 26:1. Reductive debenzylation completed the synthesis. 2′-Deoxy derivative 8 was also synthesized stereoselectively in the same manner.

Structure of acidic phospholipase A2 for the venom of Agkistrodon halys blomhoffii at 2.8Åresolution

The crystal structure of acidic phospholipase A2 from the venom of Agkistrodon halys blomhoffii has been determined by molecular replacement methods based on the known structure of Crotalus atrox PLA2, a same group II enzyme. The overall structures, except the calcium-binding regions, are very similar to each other. A calcium ion is pentagonally ligated to two carboxylate oxygen atoms of Asp-49 and each carbonyl oxygen atoms of Tyr-28, Gly-30 and Ala-31. A reason why the former enzyme functions as monomeric form, while the latter one does as dimer, could be presumed by the structural comparison of these calcium-binding regions. Although Gly-32 is usually participated as a ligand in the coordination with calcium ion in group I PLA2, it is characteristically replaced to Ala-31 in the present structure, and thus the coordination geometry of calcium ion is rather different from the usually observed one.

Interaction between the left-handed Z-DNA and polyamine-2: The crystal structure of the d(CG)3 and spermidine complex

This paper deals with the crystal structure of d(CG)3‐spermidine complex. The DNA fragment, d(CG)3, was crystallized with N‐(2‐amino‐propyl)‐1,4‐diamino‐butane, PA(34), spermidine. The results of its X‐ray crystallographic analysis showed many intermolecular contacts between d(CG)3 and spermidine, but the binding mode of spermidine to the d(CG)3 molecule is different from that of the d(CG)3 and N‐(2‐amino‐ethyl)‐1,4‐diamino‐butane [PA(24)]complex: a spermidine molecule bound to the d(CG)3 and its symmetrically related neighboring d(CG)3 molecules through the water molecules with hydrogen bonds, while one PA(24) molecule connected directly to one d(CG)3 molecule, but not to its neighboring d(CD)3 molecule. In the crystal, the d(CG)3 molecule was the left‐handed Z‐form, and three magnesium cations and a sodium cation were observed around the d(CG)3 moiety with different binding modes from the case of the d(CG)3‐PA(24) complex.

Structure of 5-methoxy-2-{[4-methoxy-3,5-dimethyl-2-pyridinylmethyl]sulfinyl}-1H-benzimidazole (omeprazole)

C17H19N3O3S, Mr = 345.42, triclinic, P1, a = 10.686 (5), b = 10.608 (7), c = 9.666 (6) A, alpha = 119.75 (5), beta = 112.02 (5), gamma = 68.33 (4) degrees, V = 859 (1) A3, Z = 2, Dm = 1.332 (2), Dx = 1.335 g cm-3, Cu K alpha, lambda = 1.5418 A, mu = 18.04 cm-1, F(000) = 364, T = 293 K, R = 0.057 for 1962 observed reflections. The methylsulfinyl group, which adopts a trans conformation, links the pyridine and benzimidazole rings in an almost coplanar orientation. Thus the molecule, as a whole, adopts a nearly extended form. Two centrosymmetrically related molecules form a cyclic dimer by intermolecular N-H...O hydrogen bonding, and the dimers are held together by van der Waals contacts between the neighboring aromatic rings in the crystal structure.

Interaction between left‐handed Z‐DNA and polyamine — 3 The crystal structure of the d(CG)3 and thermospermine complex

The DNA fragment, d(CG)3, was co‐crystallized with N‐(3‐amino‐propyl)‐N‐(5‐aminopropyl)‐1,4‐diaminobutane (thermospermine; PA(334)), a polyamine metabolized from the nucleic acid. By using a good crystal with dimensions of 0.5 × 0.5 × 0.5 mm3, X‐ray intensity data were collected up to 1.0 Å resolution. Two thermospermine molecules and a magnesium cation were bound to the left‐handed double‐helical d(CG)3 molecule. The d(CG)3 molecule adopted the left‐handed Z‐conformation and two thermospermine molecules and a magnesium cation neutralized the negative charges of the phosphate groups of the d(CG)3 molecule. Furthermore, the binding modes between d(CG)3 and thermospermine were different from those of d(CG)3 complexes with PA(24), spermidine and spermine. This is the first case in which it was determined by X‐ray crystallographic analysis that one of two thermospermine molecules bound three d(CG)3 duplexes which were symmetrically related to each other, and the other formed two hydrogen bonds at the N(5) and N(9) atoms with two adjacent nucleotide phosphate groups of a single d(CG)3 strand at the minor groove. Furthermore, no direct coordination bond was found between the d(CG)3 molecule and the magnesium cation.