Stachybotrin C and parvisporin, novel neuritogenic compounds, were isolated from the culture broth of Stachybotrys parvispora F4708. Stachybotrin C induced significant neurite outgrowth in PC12 cells and showed cell survival activity in the primary culture of cerebral cortical neurons. Parvisporin demonstrated only weak neuritogenic activity.

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The structures of stachybotrin C and parvisporin have been determined by spectroscopic analyses and chemical derivatization. Stachybotrin C contains a unique pyrano-isoindolinone ring system, while parvisporin has a hydroxyl farnesyl phenol structure.

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TMC-2A (1), -2B (2) and -2C (3), novel dipeptidyl peptidase IV (DPIV) inhibitors, were isolated from the fermentation broth of Aspergillus oryzae A374. TMC-2A, -2B and -2C inhibited rat kidney DPIV with 1C₅₀ value of 8.1 μM, 17μ, and 20μ, respectively, as well as human DPIV prepared from mononuclear cells and adenocarcinoma cells. TMC-2 compounds inhibited only DPIV among the proteases tested, indicating their high selectivity for DPIV. The kinetic analyses revealed that TMC-2A was an uncompetitive inhibitor. Taxonomy and fermentation of the producing strain are also described.

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New dipeptidyl peptidase IV inhibitors, TMC-2A, -2B, and -2C, were isolated from the fermentation broth of Aspergillus oryzae A374. On the basis of chemical, spectroscopic and X-ray crystallographic analyses, their structures were established to be peptide-like compounds composed of three moieties, L-tryptophan, mono- or dihydroxy-L-leucine and highly substituted isoquinoline.

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GE3, a novel cyclic hexadepsipeptide antibiotic, was isolated from the culture broth of Streptomyces sp. GE3. GE3 was weakly active against some Gram-positive and Gram-negative bacteria and showed potent cytotoxicity against human tumor cell lines. GE3 also exhibited antitumor activity against human pancreatic carcinoma, PSN-1, in vivo. GE3B, a linear peptide form of GE3, which was isolated from the same culture broth with GE3, showed no antibiotic and cytotoxic activities, suggesting the necessity of the cyclic structure of GE3 for its biological activities.

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A novel product, isolated from a culture broth of Actinoplanes ianthinogenes fermented for producing purpuromycin, was purified and its structure established on the basis of physico-chemical data and chemical reactions. The new product resulted to be structurally related to griseorhodins, a group of hydroquinonic antibiotics obtained from Streptomyces californicus.
This compound showed a weak activity against Gram-positive and resulted inactive against Gram-negative bacteria and Candida albicans.

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Borrelidin, an antibiotic from Streptomyces rochei, was found to be an angiogenesis inhibitor in a rat aorta matrix culture model which forms capillary vessels in vitro. Borrelidin strongly inhibited capillary tube formation with a 50%-inhibitory concentration value of O.SnM, and decreased the number of capillary tubes within 24 hours when added after maturation of tube formation. Borrelidin remarkably disrupted capillary tubes in a dose-dependent manner, by inducing apoptosis of the tube-forming cells.

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Vancomycin, LY264826 and four N-substituted derivatives of LY264826 were examined for dimerization, binding to D-alanyl-D-alanine- and D-alanyl-D-lactate-containing cell wall ligands, and binding to bacterial membrane vesicles. The six glycopeptide antibiotics represent a 360-fold range in antibacterial activities against Micrococcus luteus (MIC = 0.00072 - 0.26 μM) with the N-substituted compounds having the lowest MICs. Vancomycin, LY264826 and the four N-substituted derivatives shared nearly identical binding affinities for N, N'-diacetyl-L-lysyl-D-alanyl-D-alanine (Kb=1.5×10⁵-5.9×10⁵M^-1). Affinities for binding N, N'-diacetyl-L-lysyl-D-alanyl-D-lactate were lower but also represented a narrow range (K_b = 0.24×10³-1.6×10³M^-1). In contrast to ligand binding, the relative capacity of the six compounds to dimerize differed by four orders of magnitude (K_dim = 4.9×10¹-1.2×10⁶M^-1). The N-substituted derivatives had the highest K_dim values, required the greatest molar excess of exogenous cell wall ligand to suppress inhibition, and demonstrated a propensity to bind to bacterial membrane vesicles. The derivatives with the most lipophilic side chains were the most highly bound to vesicles. The findings suggest that the enhanced antibacterial activities of N-substituted derivatives of LY264826 derive from the nature of the hydrophobic side chain which can have a marked effect on dimerization and membrane binding.

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5, 6-Dihydrobenzo[α]naphthacenequinone has been constructed by DIELS-ALDER reaction of an outer-ring diene with a naphthoquinone regioselectively. Similarly, the 14-hydroxy-5, 6-dihydrobenzo[α]naphthacenequinone (13) has also been synthesized via the reaction of vinylketene acetal (11) with naphthoquinone.

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