A new D-glucose-6-phosphate phosphohydrolase (G6Pase) inhibitor, CJ-21, 164 (I) was isolated from the fermentation broth of the fungus Chloridium sp. CL48903. The structure was elucidated to be a novel tetramer of the salicylic acid derivatives by spectroscopic analyses. Compound I inhibited G6Pase in rat liver microsomes with an IC₅₀ of 1.6μM. Glucose output from hepatocytes isolated from rat liver was inhibited when I was present in the incubation medium, consistent with the role of I as a G6Pase inhibitor.

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Kosinostatin, a quinocycline antibiotic was isolated from the culture broth of an actinomycete strain TP-A0468 along with isoquinocycline B. The producing strain was isolated from the seawater sample collected in Toyama Bay and identified as Micromonospora sp. based on the taxonomic study. Kosinostatin was obtained from the culture fluid by solvent extraction and ODS column chromatography. Kosinostatin inhibited the growth of Gram-positive bacteria strongly (MIC=0.039μg/ml) and Gram-negative bacteria and yeasts moderately (MIC=1.56-12.5μg/ml). It showed cytotoxicity against various cancer cell lines with the IC₅₀ of 0.02-0.6μM and inhibited human DNA topoisomerase IIα with the IC₅₀ of 3-10μM.

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A quinocycline antibiotic, kosinostatin, was isolated from the culture broth of Micromonospora sp. TP-A0468 along with isoquinocycline B. Structure of kosinostatin was determined to be the stereoisomer of isoquinocycline B regarding to the stereochemistry at the C-2' spiro carbon by NMR analysis. Kosinostatin isomerizes to isoquinocycline B through the inversion of the stereocenter at C-2'. Comparison of physico-chemical properties indicated that kosinostatin is presumably identical with quinocycline B isolated by CELMER et al. from Streptomyces aureofaciens.

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Streptomyces platensis (strain NRRL 18993), a producer of dorrigocins, was shown to produce migrastatin, a cyclic congener of dorrigocin A previously reported from a different organism. Additionally a new compound isomeric to migrastatin, isomigrastatin, was also isolated and its structure was determined to be a cyclic form of dorrigocin B. Both compounds were fully characterized from MS and NMR data. Product titers of both were improved by the addition of XAD-16 resin to the fermentation medium.

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Macrosphelide L has been isolated from a strain of Periconia byssoides originally separated from the sea hare Aplysia kurodai, and the absolute stereostructures of this material and macrosphelide H, previously undetermined, have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and some chemical transformation. (R)-Methyl 3-p-bromobenzoyloxy-5-oxohexanoate has been synthesized for configurational assignments of macrosphelide H. These macrosphelides inhibited the adhesion of human-leukemia HL-60 cells to HUVEC.

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Two novel compounds, stachyflin and acetylstachyflin, have been isolated by solid-state fermentation of Stachybotrys sp. RF-7260. The structures of both metabolites, determined by detailed NMR analyses and X-ray crystallographic analysis, are novel with a pentacyclic moiety including cis-fused decalin. The absolute stereochemistry of stachyflins was determined by circular dichroism analysis. Stachyflin showed antiviral activity against influenza A virus (H1N1) in vitro with an IC₅₀ value of 0.003μM. Acetylstachyflin was about 77-fold less active than stachyflin.

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Stachyflin and acetylstachyflin, produced by Stachybotrys sp. RF-7260, were found to have potent anti-influenza A virus activity. Stachyflin is a new class of hemagglutinin fusion inhibitors of influenza A virus. Several derivatives were synthesized from acetylstachyflin and subjected to preliminary examination of their structure-activity relationships. Among them, the 3-oxo and 3, 8'-dioxo derivatives showed potent antiviral activity similar to stachyflin. The 3-epi derivative was four times less active than stachyflin. Modification of the 6'-hydroxy group and the C-5' position markedly diminished the antiviral activity.

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Talaromyces flavus FKI-0076, a soil isolate, was found to produce compounds which reinforce the anti-Candida albicans activity of miconazole. Four structurally related compounds, a novel one, designated actofunicone, and the knowns deoxyfunicone, vermistatin and NG-012, were isolated from the culture broth by solvent extraction, ODS column chromatography and HPLC. The structure of actofunicone was elucidated as benzoic acid, 3, 5-dimethoxy-2-[[4-oxo-6-(2-acetyloxy propyl)-4H-pyran-3-yl]carbonyl]-, methyl ester by various spectroscopic analyses including NMR experiments. These compounds potentiated the anti-C. albicans activity of miconazole, decreasing the IC₅₀ value of miconazole from 19μM to 1.6-3.7μM in the presence of the funicones.

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The synthesis and structural determination of a number of new rhodomycin derivatives, modified in the sugar part are described. The cytotoxicity against leukemic L1210 cells of these compounds is reported, along with β-rhodomycinone and two regioisomers of the above compounds, which were isolated during the synthetic procedure.

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The novel natural antibiotics pyloricidin A, B and C, which possess potent and highly selective anti-Helicobacter pylori activity, were synthesized from D-galactosamine as a chiral template for the common (2S, 3R, 4R, 5S)-5-amino-2, 3, 4, 6-tetrahydroxyhexanoic acid moiety. The synthetic strategy, using 2-amino-2-deoxyuronic acid derivatives as key intermediates, was also useful to prepare a series of derivatives modified at the β-D-phenylalanine and with altered stereochemistry on the 5-amino-2, 3, 4, 6-tetrahydroxyhexanoic acid moiety. From the drastic decrease of their anti-H. pylori activity, it was clear that the β-D-phenylalanine part and the stereochemistry of the 5-amino-2, 3, 4, 6-tetrahydroxyhexanoic acid moiety were significant for the activity.

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