Masahiko Bando

Novel sesquiterpene esters with alkaloid and monoterpene and related compounds from Tripterygium hypoglaucum: A new class of potent anti-HIV agents

Abstract Two new sesquiterpene polyol esters (triptonine A and B) with alkaloid and monoterpene were isolated from Tripterygium hypoglaucum (Levl.) Hutch. Their structures were elucidated by spectroscopic means and X-ray analysis. Triptonine A ( 1 ) and hypoglaunine B 3) ( 4 ) demonstrated potent anti-HIV activity with EC 50 values of 2.54 and 0.13μg/ml and therapeutic index values of 39.4 and >1000, respectively.

An efficient synthesis of pironetins employing a useful chiral building block,(1S,5S,6R)-5-hydroxybicyclo[4.1.0]heptan-2-one

Abstract A convergent total synthesis of pironetin1 and related compound2 using a chiral building block,(1S,5S,6R)-5-hydroxybicyclo[4.1.0]heptan-2-one5 is described. Both the dithiane47 and the epoxide32 with proper substituents were employed as coupling partners to construct the whole carbon skeleton48, which was converted to (−)-pironetin1 and (−)-2 in few steps. The usefulness of5 for polyketide synthesis was demonstrated. Download : Download full-size image

Di- and triterpenoids from Tripterygium hypoglaucum

Abstract The methanol extract of dried root outer bark of Tripterygium hypoglaucum (Levl.) Hutch afforded five new triterpenes: 2,3-seco-2,24-epoxy-D:A-friedoolenane-2, 24-olide-29-oic acid named celastolide, 2,23-dihydroxy-3-methoxy-6-oxo-1,3,5(10), 8-tetraene-24-nor-D:A-friedoolenane-29-oic acid, 2-hydroxy-3-methoxy-6-oxo-1,3,5(10), 8-tetraene-24-nor-D:A-friedoolenane-29-oic acid, 2,3-dihydroxy-1,3,5(10), 8-tetraene-24-nor-D:A-friedoolenane-29-oic acid and 3β,11α-dihydroxy-13(18)-ene-oleanane named triptohypol A, B and C and hypodiol, and two new diterpenes: 3β,14,19-trihydroxy-abieta-8,11,13-triene and 7-oxo-11,13-dihydroxy-19(4-3)-abeo-abieta-3,8,11,13-tetraene-19,18-olide named triptobenzene J and K, and 18 known compounds. Their structures were established on the basis of chemical and spectroscopic studies.

NOVEL AND VERSATILE SYNTHESIS OF PYRROLIDINE TYPE AZASUGARS, DAB-1 AND LAB-1, POTENT GLUCOSIDASE INHIBITORS

Abstract Synthesis of glucosidase inhibitors, DAB-1 (1) and LAB-1 (2) from diethyl tartrate is described. The procedure afforded an epimerizable mixture of diastereomeric intermediates 8 and ent. 8, and opened the door not only to the selective synthesis of DAB-1 and LAB-1 but for giving various related analogs.

Synthesis and Structure of Orobanchol, the Germination Stimulant forOrobanche minor

The structure of orobanchol, a new seed germination stimulant for clover broomrape (Orobanche minor), was proposed as 5a (tentative absolute configuration) on the basis of GC-MS comparison of the natural product with several synthetic compounds [(±)-4a–(±)-4h, (±)-5a and (±)-5b]. All of the synthetic compounds showed significant seed germination activities for Orobanche minor and witchweed (Striga asiatica).

Synthesis and Biological Evaluation of the Four Racemic Stereoisomers of the Structure Proposed for Sorgolactone, the Germination Stimulant from Sorghum bicolor

Abstract The synthesis of the racemates of the structure 1 proposed for sorgolactone and its three stereoisomers was achieved by confirming the stereostructures of the intermediate (±)- 6 and the final product (±)- 1 by X-ray analyses. Biological evaluation of the products employing clover broomrape ( Orobanche minor ) seeds revealed that the order of activity as a germination stimulant was (±)-strigol ≈ (±)- 9 ≥ (±)- 12 > (±)- 1 > (±)- 11 .

Structural analysis of human glutamine:fructose-6-phosphate amidotransferase, a key regulator in type 2 diabetes

Glutamine:fructose‐6‐phosphate amidotransferase (GFAT) is a rate‐limiting enzyme in the hexoamine biosynthetic pathway and plays an important role in type 2 diabetes. We now report the first structures of the isomerase domain of the human GFAT in the presence of cyclic glucose‐6‐phosphate and linear glucosamine‐6‐phosphate. The C‐terminal tail including the active site displays a rigid conformation, similar to the corresponding Escherichia coli enzyme. The diversity of the CF helix near the active site suggests the helix is a major target for drug design. Our study provides insights into the development of therapeutic drugs for type 2 diabetes.

SYNTHETIC DISPROOF AGAINST THE STRUCTURE PROPOSED FOR ALECTROL, THE GERMINATION STIMULANT FROM VIGNA UNGUICULATA

Abstract Several compounds [(±)-3a, (±)-3b, (±)-10, (±)-11 and (±)-12] with the structures related to that (3) proposed for alectrol, the germination stimulant, were synthesized. The structure (±)-3a was solved by X-ray crystallographic analysis. Comparison of the 1H NMR data of the synthetic compounds with those reported for alectrol disproved the correctness of the proposed structure 3.

Enantioselective Synthesis of the Metabolites of Vasopressin V2 Receptor Antagonist OPC-31260 via Lipase-Catalyzed Transesterification

Abstract The optical isomers of 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine (OPC-31260, 1) and its metabolites (2, 3, 4, 5 and 6) were enantioselectively synthesized. The chiral acetate 8b and alcohol 7a were prepared via the resolution of the racemic alcohol (±)-7 using the lipase-mediated transesterification in vinyl acetate. The compounds 8b and 7a were converted to the hydroxy metabolites (2a and 2b), the methylamine metabolites (3a and 3b), the dimethylamines (1a and 1b), and the amine metabolites (4a and 4b) in several steps while maintaining their absolute configurations. The 4,5-diol metabolites (5a, 5b, 6a and 6b) were synthesized from the key intermediates obtained by the lipase-catalyzed transesterification.

Syntheses of (±)- and (+)-Sorgolactone, the Germination Stimulant fromSorghum bicolor

Syntheses of (±)-2a, the racemate of the structure proposed for sorgolactone, and its three racemic stereoisomers have been accomplished with confirmation of the stereostructures of the intermediate (±)-10 and the final product (±)-2a by X-ray analysis. Its optically active form, (3aR,8S,8bS,2′R)-(+)-2a, has also been prepared from (S)-(–)-citronellal by employing radical cyclization of 18 to 19 as the key step. Spectroscopic properties of the synthetic products are compared with those reported for natural sorgolactone. Bioassays using clover broomrape (Orobanche minor) seeds have revealed that all the stereoisomers strongly stimulate their germination.