No abstract

As the first non-peptide endothelin receptor antagonist from a higher plant, a new triterpenoid, myriceric acid A (50-235) (1) was isolated from the bayberry, Myrica cerifera. Myriceric acid A (1) inhibited not only an endothelin-1-induced increase in cytosolic free Ca2+ concentration (IC50 = 11 +/- 2 nM) but [125I]endothelin-1 binding in rat aortic smooth muscle cells (Ki = 66 +/- 15 nM). Two new related triterpenoids, myriceric acid C (6), and myriceric acid D (8), were also isolated. Furthermore, the chemical modification of these natural products led to the synthesis of sulfated derivatives (13, 14, 15) which showed 1.5 to 20 times higher affinity for endothelin receptors. The structure activity relationships of myriceric acids and their derivatives are discussed.

New inhibitors of aldose reductase, designated salfredins A3, A4, A7, Cl5 C2, C3 and Bll5 were isolated from the fermentation broth of Crucibulum sp. RF-3817 by successive purification procedures of solvent extraction, silica gel column chromatographies and reverse-phase HPLC.Their structures were established by spectroscopic methods, including UV, SI-MS and NMR. The structures of salfredins A4 and B1 ]L were confirmed by X-ray crystallographic analysis.Aldose reductase (Alditol:NADP+ oxidoreductase, EC1.1.1.21) plays a key role in the "polyol pathway", and inhibition of this enzyme represents a new pharmacological approach towards the treatment of certain chronic complications of diabetes mellitus1~3).In a screening program for unique microbial products with pharmacological activity, new aldose reductase inhibitors4' 5), designated as salfredins A3 (la), A4 (2a), A7 (3a), Ci (4a), C2 (5a), C3 (6a) and B1X (7a), were isolated from the fermentation broth of Crucibulum sp. RF-3817. The taxonomy, fermentation, isolation, physico-chemical properties and structures of salfredin congeners are described in this paper. Their biological properties will be reported in a following paper (in preparation). TaxonomyThe strain RF-3817 was isolated as follows. First, peridioles within the peridium formed on a rotten wood block were immersed in a solution of sodium hypochlorite for one minute to sterilize the surface of the peridioles. Next, the peridioles were washed with sterile water and the basidiospores formed within the peridioles were placed on an appropriate mediumto isolate the strain. On the hyphae of the strain grown on the medium,clamp connections were observed, the width of each hypha being 1 to 5/mi. The peridium of the strain formed on the rotten wood block is pyriform, 5 to 8mm in height, 4 to 6mm in diameter, and has an ocher color. In the upper portion of the peridium, there is an epiphragm having a pale yellowish-white color, which will dehisce when matured.Within the peridium are lenticular peridioles. The peridioles, 1 to 1.5mm in size, are attached by funiculi to the inner wall of the peridium. Within the peridioles, basidiospores, 3 to 5 by 7 to 10fim, are formed. These properties were compared with the characteristics of other genera belonging to the order Nidulariales,

Safety evaluation for ozonolysis of β-pinene was conducted using DSC, ARC, and RC1e. ARC measurement showed that the concentration of the ozonized mixture affects its thermal stability. The sample at a high concentration of 1.83 mol/L was very unstable even at room temperature and decomposed rapidly. ADT24 of the diluted sample of 0.73 mol/L was 28.2 °C. Although reductive decomposition of the ozonized mixture at extremely low temperature is very dangerous because of accumulation of the heat of reaction, its process temperature was validated to not exceed the ADT24. As a result, pilot manufacturing on a 300-L reactor scale could be achieved.