Rodney W. Rickards

Calothrixins A and B, novel pentacyclic metabolites from Calothrix cyanobacteria with potent activity against malaria parasites and human cancer cells

Abstract Cell extracts from photoautrophic cultures of two cyanobacterial Calothrix isolates inhibited the growth in vitro of a chloroquine-resistant strain of the malaria parasite, Plasmodium falciparum, and of human HeLa cancer cells, in a dose-dependent manner. Bioassay-directed fractionation of the extracts led to the isolation and structural characterization of calothrixins A (1) and B (2), pentacyclic metabolites with an indolo[3,2-j]phenanthridine ring system unique amongst natural products, which exert their growth-inhibitory effects at nanomolar concentrations.

Allelopathic actions of the alkaloid 12-epi-hapalindole E isonitrile and calothrixin A from cyanobacteria of the genera Fischerella and Calothrix

The alkaloids 12-epi-hapalindole E isonitrile,isolated from the cyanobacterium Fischerellasp., and the indolophenanthridine calothrixin A, fromCalothrix sp., were characterized in terms oftheir ability to kill several organisms and celltypes, and their biochemical modes of action. Bothcompounds inhibited RNA synthesis, and consequentlyprotein synthesis, in Bacillus subtilis. Calothrixin A also inhibited DNA replication, thehapalindole having little effect on this process. Measurements of in vitro RNA synthesis confirmedthe in vivo results and suggested that bothcompounds inhibit RNA polymerase directly; the degreeof inhibition was independent of the DNAconcentration, but strongly dependent on thepolymerase concentration.

Biomimetic synthesis of the microbial elicitor syringolide 2

Abstract Syringolide 2 ( 1 ; n=2), an elicitor metabolite of the bacterial plant pathogen Pseudomonas syringae pv. tomato , has been synthesised in four steps from D-xylulose. The key stage involves triple cyclisation of the putative biosynthetic intermediate 1-(3′-oxodecanoyl)-D-xylulose ( 9 ), and provides evidence for the biosynthesis of the syringolides.

The structure and some aspects of the biosynthesis of pleuromutilin

Abstract Evidence is presened which confirms the structure I for pleuromutilin. The specific incorporation of [ 14 C] acetic and mevalonic acids verifies its diterpenoid nature, and some aspects of its stereochemistry are discussed.

Cyclopentamoids from phenol. Part VII. Preparation and reactions of a 3-hydroxy-5-oxocyclopent-1-enyl carbanion equivalent

Abstract (3 S * , 5 R * )-1-Lithio-5-( t -butyldimethylsilyloxy)-3-(tetrahydropyran 2-yloxy)cyclopent-1-ene (7) is prepared from phenol via the chlorocyclopentenone (1) and the stannylcyclopentenediol derivative (6); this latent 3-hydroxy-5-oxocyclopent-1-enyl carbanion (7) reacts efficiently with various electrophiles to form substituted cyclopentenediol derivatives (8) which can be converted into the corresponding 2-substituted 4-hydroxycyclopent-2-enones (9).

3-Amino-5-hydroxybenzoic acid as a key intermediate in ansamycin and maytansinoid biosynthesis

The specific incorporation of 3-amino-5-hydroxybenzoic acid (2) into actamycin (1) by a Streptomycete culture establishes this amino-acid as a key intermediate in ansamycin and maytansinoid biosynthesis.

Biosynthesis of the mitomycin antibiotics from 3-amino-5-hydroxybenzoic acid

The efficient, specific incorporation of isotope from [carboxy-13C]-3-amino-5-hydroxybenzoic acid into the C-6 methyl group of porfiromycin by Streptomyces verticillatus establishes this amino-acid as the biogenetic precursor of the methylbenzoquinone nucleus of the mitomycin antibiotics.

An expedient synthesis of 3-amino-5-hydroxy- benzoic acid and its n-alkyl analogues

Abstract The natural aromatic amino acid 1, an intermediate in the biosynthesis of several important groups of antibiotics, and its N-alkyl derivatives are efficiently prepared by direct amination of 3,5-dihydroxybenzoic acid.

Characterization of a juvenile hormone binding lipophorin from the blowfly Lucilia cuprina.

The larval haemolymph of the sheep blowfly Lucilia cuprina (Weidemann) contains a juvenile hormone binding protein with a Kd for racemic JH III of 33 +/- 6 nM. The density of the binding sites is 212 +/- 33 pmol/mg haemolymph protein. The binding protein is equally specific for JH III and methyl farnesoate. Some natural juvenoids were ranked for their ability to displace [3H]JH III with JH III > JH II > JH I > JH III acid > JH III diol > JHB3 = no detectable displacement. These data, together with displacement studies for 14 synthetic juvenoids, indicate some characteristics of the JH binding cleft. The binding protein is a high density lipophorin (density = 1.15 g/ml) and has subunit molecular weights of 228 kDa (apolipophorin I) and 70 kDa (apolipophorin II). The N-terminal amino acid sequences of the subunits have no discernible homology to any previously sequenced protein. Lipophorin-specific immunocytochemical staining occurs in a subset of fat body cells.

Electrocyclic processes in aromatic biosynthesis: a biomimetic study of pseudorubrenoic acid A

The possible involvement of 6π electrocyclic ring closures, mediated by electrocyclase enzymes, of polyunsaturated acyclic polyketide intermediates in the biosynthesis of certain o-dialkyl-substituted benzenoid natural products is discussed. The feasibility of the process is illustrated by the electrocyclic ring closure of 7E,9Z,11E,13Z-1-t-butyldimethylsilyloxy-hexadeca-7,9,11,13-tetraene (12a) to the cyclohexadiene 13 followed by dehydrogenation to the analogue 14 of the o-dialkyl-substituted aromatic metabolite pseudorubrenoic acid A (1).