Hiroshi Naganawa

Caprazamycins, Novel Lipo-nucleoside Antibiotics, from Streptomyces sp : II. Structure Elucidation of Caprazamycins

Novel antibiotics, active against acid-fast bacteria, caprazamycins, were isolated from the culture broth of Streptomyces sp. MK730-62F2. The planar structures of the compounds were determined by 2D NMR spectroscopic study. Furthermore, the absolute structure of caprazamycin B (2) was established by NMR spectroscopy and X-ray crystallography of its degradation products and by total synthesis of the 5-amino-5-deoxy-D-ribose moiety. In the course of degradation studies of 2 under alkaline and acidic conditions, we obtained the two core components, caprazene (11) and caprazol (14), respectively, in high yield.Structurally, caprazamycins belong to a family of lipo-uridyl antibiotics, which have been discovered as specific inhibitors of a bacterial translocase.

Bacilysocin, a Novel Phospholipid Antibiotic Produced by Bacillus subtilis 168

ABSTRACT We have found a novel phospholipid antibiotic (named bacilysocin) which accumulates within (or associates with) the cells of Bacillus subtilis 168 and determined the structure by nuclear magnetic resonance and mass spectrometry analyses. The structure of bacilysocin elucidated was 1-(12-methyltetradecanoyl)-3-phosphoglyceroglycerol. Bacilysocin demonstrated antimicrobial activity, especially against certain fungi. Production of bacilysocin commenced immediately after growth ceased and before the formation of heat-resistant spores. The production of bacilysocin was completely blocked when the ytpA gene, which encodes a protein homologous to lysophospholipase, was disrupted, but blockage of the ytpA gene did not significantly affect growth. Sporulation was also impaired, with a 10-fold reduction in heat-resistant spore titers being detected. Since the ytpA disruptant actually lacked phospholipase activity, we propose that the YtpA protein functions as an enzyme for the biosynthesis of bacilysocin.

A Novel Bridged Stilbenoid Trimer and Four Highly Condensed Stilbenoid Oligomers in Vatica rassak.

Abstract Vaticanol G ( 1 ) and vaticaside D ( 2 ) isolated from stem bark of Vatica rassak (Dipterocarpaceae) were the first instance of stilbenoid trimers with an unusual tribenzobicyclo[3.3.2]decatriene system. Vaticanols D ( 3 ) and H ( 4 )–J ( 6 ) were elucidated to be a stilbenoid hexamer or heptamer containing a structurally identical trimeric unit. Their structures and the relative configurations were established on the basis of 2D NMR spectroscopy. The hexamers ( 3 , 4 and 5 ) and the heptemer ( 6 ) showed cytotoxicity against KB cells.

Two new oligostilbenes with dihydrobenzofuran from the stem bark of Vateria indica

Abstract Two new stilbenoids, vateriaphenols A ( 1 ) and B ( 2 ), were isolated from the stem bark of Vateria indica along with known 10 stilbenoids ( 3–12 ) and bergenin ( 13 ). The structures of isolates were established based on spectroscopic analysis. The structures of vateriaphenols A and B were characterized as an octamer and a tetramer of resveratrol, respectively. The spectral properties of the highly condensed vateriaphenol A were also discussed.

Inhibition of cellular phosphatidylinosito, turnover by psi-tectorigenin

Psi‐tectorigenin, an isoflavonoid, was isolated from a culture filtrate of actinomycetes as an inhibitor of epidermal growth factor‐induced phosphatidylinositol turnover in cultured A431 cells. It inhibited phosphatidylinositol turnover with an IC50 of about 1 μg/ml; thus, its inhibitory activity was 6‐times stronger than that of genistein or orobol. When added to cultured A431 cells psi‐tectorigenin inhibited phosphatidylinositol turnover without inhibiting epidermal growth factor receptor tyrosine protein kinase. Thus, psi‐tectorigenin is a specific inhibitor of phosphatidylinositol turnover and may be a useful tool for the functional analysis of phosphatidylinositol turnover.

Polyoxypeptin isolated from Streptomyces: A bioactive cyclic depsipeptide containing the novel amino acid 3-hydroxy-3-methylproline

Abstract Polyoxypeptin, a potent inducer of apoptosis in human pancreatic carcinoma cells, was isolated from an ethyl acetate extract of a Streptomyces culture broth. Structural determination by 2D-NMR and X-ray crystallographic analysis revealed that it is a novel cyclic hexadepsipeptide containing five hydroxylated amino acids. The unusual and hitherto unreported amino acid 3-hydroxy-3-methylproline was one of them.

A new bioactive steroidal saponin, furcreastatin, from the plant Furcraea foetida.

Microbial and plant secondary metabolites were screened for compounds that are selectively cytotoxic to mutant p53-expressing mouse fibroblasts. As a result, furcreastatin, a novel steroidal saponin, was isolated from an EtOH extract of the leaves of Furcraea foetida. Furcreastatin consisted of hecogenin as the aglycone and a hexasaccharide containing D-galactose, L-rhamnose and four D-glucose residues. The structure was determined to be (3 beta,5 alpha,25R)- 3-hydroxyspirostan-12-one 3-O-[alpha-L-Rhap-(1-->4)-beta-D-Glcp-(1-->3)-¿beta-D-Glcp-(1-->3) -beta-D- Glcp-(1-->2)¿-beta-D-Glcp-(1-->4)-beta-D-Galp] by extensive NMR spectroscopic studies. Furcreastatin decreased the viability of mutant p53-over-expressing cells with an ED50 of 4.0 micrograms/mL, and decreased that of the parental cell-line with an ED50 of 9.6 micrograms/mL.

A new resveratrol octamer, vateriaphenol A, in Vateria indica

Abstract A novel resveratrol octamer, vateriaphenol A, was isolated from stem bark of Vateria indica (Dipterocarpaceae). The structure and the relative configuration were confirmed on the basis of 1D and 2D NMR spectral data. Vateriaphenol A showed cytotoxicity against KB cells.

Vaticanol D, a novel resveratrol hexamer isolated from Vatica rassak

Abstract Vaticanol D isolated from the bark of Vatica rassak is the first instance of a resveratrol hexamer. The structure and relative configuration were established by means of 2D NMR spectroscopy. Vaticanol D possessed a scavenging activity of super oxide.

Akaterpin, a novel bioactive triterpene from the marine sponge Callyspongia sp.

Akaterpin (1), an inhibitor of phosphatidylinositol-specific phospholipase C, was isolated from an acetone extract of the marine sponge, Callyspongia sp. Structural determination by 2D-NMR spectroscopy revealed that it was a novel triterpene with the hydroquinone disulfate.