5-N-acetylardeemin, a novel heterocyclic compound which reverses multiple drug resistance in tumor cells. II. Isolation and elucidation of the structure of 5-N-acetylardeemin and two congeners.

A family of novel compounds has been detected and isolated following an assay for the attenuation of multiple drug resistance in tumor cells from the fermentation broth and mycelia of a strain of Aspergillus fischeri which we have designated var. brasiliensis. The structures of three components were determined employing 1-D and 2-D homonuclear and heteronuclear NMR spectroscopy and mass spectrometry. The structure of 5-N-acetylardeemin was confirmed by single crystal X-ray diffraction. These compounds are most closely structurally related to asperlicin E1).

Stereocontrolled synthesis of psi[CH = CH] dipeptide isosteres.

A new stereocontrolled synthesis of the psi[CH = CH] dipeptide isostere is described. They key step of the sequence relies on the stereospecific alpha-alkylation of delta-amino-gamma-mesyloxy-alpha,beta-unsaturated esters. The broad availability of nucleophilic alpha-side chains by this method allows the preparation of a wide variety of psi[CH = CH] isosteres with predictable stereochemistry.

Azido glycols: potent, low molecular weight renin inhibitors containing an unusual post scissile site residue.

Azidomethyl-substituted 1,2- and 1,3-diols were prepared from Boc-cyclohexylalanal and evaluated as transition state analogue renin inhibitors, leading to the development of a small (MW less than 600), nanomolar inhibitor. Remarkable aqueous solubility enhancement followed the incorporation of an N-terminal urea functionality. Evaluation of selected compounds both in vivo and in vitro demonstrated that while transport across the intestine occurred upon id administration, extensive liver extraction resulted in low systemic levels.

Arizonins, a new complex of antibiotics related to kalafungin. II. Isolation and characterization.

A new complex of anti-Gram-positive antibiotics was produced by the fermentation of Actinoplanes arizonaensis sp. nov. The antibiotics were recovered from the fermentation broth with Amberlite XAD-7 resin and from the mycelium by acetone lysis. UV, IR, MS and NMR spectral studies characterized these compounds as kalafungin-type antibiotics. They differ from other known members by an unusual oxidation pattern on the aromatic ring. They vary from one another by the degree and position of O-methylation on the aromatic ring and in the aliphatic portion of the molecules. The structure of one component was confirmed by X-ray diffraction analysis.

Spenolimycin, a new spectinomycin-type antibiotic. II. Isolation and structure determination.

A new water-soluble, basic antibiotic has been isolated from the fermentation beers of Streptomyces gilvospiralis sp. nov. The structure of the antibiotic has been deduced from spectral studies and confirmed by chemical degradation to spectinomycin. This structure, 3'-O-methylspectinomycin-3',4'-enol ether has led to the name spenolimycin.

Chemical self-defense by termite workers: prevention of autotoxication in two rhinotermitids.

Soldiers of the lower termites Prorhinotermes simplex and Schedorhinotermes lamanianus (Isoptera, Rhinotermitidae) have electrophilic contact poisons used in colony defense. Workers of these termites die when exposed to the defense secretion of the other species, but survive when exposed to chemicals from conspecific soldiers. Detoxication occurs by an initial substrate-specific reduction of the electron-deficient double bond of the nitroalkene (Prorhinotermes simplex) or vinyl ketone (Schedorhinotermes lamanianus) followed by complete catabolism to acetate.