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Biomedical subjects

T M Harris

Publications and source records attributed to T M Harris.

At least 109 records · Page 6Linked to original sources
PubMed1979

Biosynthesis of slaframine, (1S,6S,8aS)-1-acetoxy-6-aminooctahydroindolizine, a parasympathomimetic alkaloid of fungal origin. 3. Origin of the pyrrolidine ring.

The phytopathogen Rhizoctonia leguminicola has previously been shown to incorporate pipecolic acid into the piperidine alkaloids 1-acetoxy-6-aminooctahydroindolizine (slaframine) and 3,4,5-trihydroxyoctahydro-1-pyrindine. In the experiments described here, resting cultures of R. leguminicola were incubated with [1-14C]- and [2-14C]malonic acid and with [1-14C]- and [2-2H]acetic acid. Both acids were incorporated into the ring systems of both alkaloids. Mass spectrometric analysis of 2H-enriched slaframine showed that the label resides in the five-membered ring and that the methyl carbon of acetate is joined to the carboxyl carbon of pipecolate. A pipecolate-dependent decarboxylation of [1-14C]malonate was demonstrated in cell-free extracts of R. leguminicola. The results account for previously unattributed carbons in the two alkaloids and suggest the formation of an eight-carbon intermediate common to both alkaloids by acylation of malonate with pipecolic acid.

Acetates↗
PubMed1979

Biosynthesis of slaframine, (1S,6S,8aS)-1-acetoxy-6-aminooctahydroindolizine, a parasympathomimetic alkaloid of fungal origin. 4. Metabolic fate of ethyl pipecolylacetate, 1,3-dioxooctahydroindolizine, and 1-hydroxyoctahydroindolizine in Rhizoctonia leguminicola.

Known or suspected intermediates in the biosynthesis of slaframine and 3,4,5-trihydroxyoctahydro-1-pyrindine, piperidine alkaloids of the phytopathogenic fungus Rhizoctonia leguminicola, were prepared and tested for biological conversions. Ethyl pipecolylacetate, an analogue of the postulated condensation product of pipecolic and malonic acids (two previously identified alkaloid precursors), was insufficiently stable for feeding experiments. The lactam of pipecolylacetate, 1,3-dioxooctahydroindolizine, was degraded by the fungus without direct incorporation into alkaloids. The known slaframine precursor 1-hydroxyoctahydroindolizine was prepared by a novel route which permitted high levels of deuterium enrichment at C-1 and C-3. Mass spectrometric examination of the slaframine biosynthesized from cis- and trans-[1,3,3-2H]-1-hydroxyoctahydroindolizine strengthened arguments that 1-oxooctahydroindolizine is an intermediate in slaframine biogenesis.

Carbon Radioisotopes↗
PubMed1979

Structural investigation of the antibiotic ristomycin A. The amino acid constituents.

Hydrolysis of the O-methylated aglycone of ristomycin A by a mixture of KOH and NaBH4 yielded a mixture of aromatic amino acids which, after N-acetylation and O-methylation, were separated by chromatography on silica gel. Compounds III approximately VII were isolated and identified by pmr and mass spectroscopy. Compounds V approximately VII were also oxidatively degraded to the corresponding benzoate esters. Componds III and IV are derived from ristomycinic acid (I) and V from actinoidinic acid (II), both of which had been obtained in earlier acid hydrolyses of the antibiotic. Compounds VI and VII had not been detected previously nor glycine which was also found to be a product of base hydrolysis. It is postulated that the new products arise from bisdechlorovancomycinic acid (X). It is concluded that aglycoristomycin A comprises I, II and X which also constitute the aglycone of ristocetin A.

Amino Acids↗
PubMed1973

Production, isolation, and preliminary toxicity studies of brevianamide A from cultures of Penicillium viridicatum.

Brevianamide A, one of a novel group of alkaloids first obtained from Penicillium brevi-compactum, has also been isolated as a principal metabolite from two key isolates of P. viridicatum. Procedures for bioproduction and purification are described. This compound was not toxic when fed or injected into mice and had no antibiotic properties against several common bacterial and fungal microorganisms. Brevianamides A and B are among at least four yellow metabolites that may be formed by isolates of P. viridicatum.

Alkaloids↗