The enantioselective synthesis of (R)- and (S)-3-amino-3,4-dihydro-1H-[1,8]naphthyridin-2-one

A number of approaches to the enantioselective synthesis of (R)- and (S)-3-amino-3,4-dihydro-1H-[1,8]naphthyridin-2-one were studied. A novel one-pot asymmetric reduction/lactamization provided the desired products in high yield and enantiomeric excess.     

Antimalarial activity of a new family of analogues of manzamine A

Manzamine A represents an important lead structure for the development of novel antimalarial chemotherapies. The synthesis and biological evaluation of a group of simplified analogues of manzamine A, which were designed to examine the roles of the A and D rings and of both the relative stereochemistry and the orientation of the beta-carboline heterocycle on the antimalarial activity of manzamine A, are described. [structure: see text]     

Identification of a novel series of alkylitaconic acids in wood cultures of Ceriporiopsis subvermispora by gas chromatography/mass spectrometry.

A novel series of long-chain unsaturated dicarboxylic acids consisting of a long aliphatic chain attached to the C-3 position of itaconic acid has been identified by gas chromatography/mass spectrometry during in vitro decay of eucalypt wood by the white-rot basidiomycete Ceriporiopsis subvermispora. The major compounds were identified as tetradecyl-, 7-hexadecenyl- and hexadecylitaconic acids by their mass fragmentation patterns. Other members of the same compound series, identified as dodecanyl-, tridecanyl-, tetradecenyl-, pentadecanyl-, octadecenyl- and octadecanylitaconic acids, were present in very minor amounts or traces. Whereas hexadecenylitaconic acid has already been reported in cultures of C. subvermispora, to our knowledge this is the first report of the presence of the other alkylitaconic acids in fungal cultures. These new alkylitaconic-type metabolites may constitute a source for peroxidizable lipids involved in lignin degradation during wood decay by C. subvermispora and other white-rot basidiomycetes.     

A new and useful method for the macrocyclization of linear peptides

A new and useful procedure for the macrocyclization of linear peptides is described. The natural amino acid side chains of tyrosine (phenol), lysine (alkylamine), and histidine (imidazole) react in an intramolecular fashion with a pendent pyridine-N-oxide-carboxamide, which is selectively activated by the phosphonium salt, PyBroP. The reaction is mild, rapid, and efficient with a potentially large substrate scope. Multiple examples are provided with full characterization and analyses, including a novel aza-variant of the C-O-D ring system of vancomycin.     

General and mild preparation of 2-aminopyridines

A general and facile one-pot amination procedure for the synthesis of 2-aminopyridines from the corresponding pyridine-N-oxides is presented as a mild alternative to S(N)Ar chemistry. A variety of amines and heterocyclic-N-oxides participate effectively in this transformation which uses the phosphonium salt, PyBroP, as a means of substrate activation.     

Mild addition of nucleophiles to pyridine-N-oxides

A general and facile one-pot procedure for the synthesis of 2-substituted pyridines from the corresponding pyridine-N-oxides and nucleophiles is presented as a mild alternative to S(N)Ar chemistry. A variety of nucleophiles and heterocyclic-N-oxides participate effectively in this transformation, which uses the phosphonium salt, PyBroP, as a means of substrate activation.     

Synthetic modification of manzamine A via Grubbs metathesis. Novel structures with enhanced antibacterial and antiprotozoal properties

A strategy for the structural modification of biologically important alkene-containing natural products via ring-opening olefin metathesis is described. Exposure of manzamine A 1 to the second-generation Grubbs catalyst in the presence of ethylene leads to the formation of 2 and 4. The antibacterial activity of the novel manzamine analogue 2 (IC50=0.10 nM) against Mycobacterium intracellulare is ca. 2-fold more potent than that of ciprofloxacin (IC50=0.18 nM), a drug that is frequently used against antibiotic-resistant infections.