Condensation of C-Alkylated Malonic Ester and Urea

Synthesis of C-13-Alkylated 8-Oxoberbines

C-13-alkylated methoxy-8tf-dibenzo[a,g]quinolizin-8-ones 2a-e were synthesized by photocyclization of 1 -alkylidene-N-benzoyl-1,2,3,4-tetrahydroisoquinolines 1. Moreover, condensation of l,2,3,4-tetrahydro-6,7-dimethoxy-l-oxo-isoquinoline with homophthalic acid anhydrides 7a and b leads to the C-13-alkylated 8-oxoberbines 2b and c and improves the yields compared with those of the photocyclizat...

Specificity of the ester bond forming condensation enzyme SgcC5 in C-1027 biosynthesis.

The SgcC5 condensation enzyme catalyzes the attachment of SgcC2-tethered (S)-3-chloro-5-hydroxy-β-tyrosine (2) to the enediyne core in C-1027 (1) biosynthesis. It is reported that SgcC5 (i) exhibits high stereospecificity toward the (S)-enantiomers of SgcC2-tethered β-tyrosine and analogues as donors, (ii) prefers the (R)-enantiomers of 1-phenyl-1,2-ethanediol (3) and analogues, mimicking the e...

A free-standing condensation enzyme catalyzing ester bond formation in C-1027 biosynthesis.

Nonribosomal peptide synthetases (NRPSs) catalyze the biosynthesis of many biologically active peptides and typically are modular, with each extension module minimally consisting of a condensation, an adenylation, and a peptidyl carrier protein domain responsible for incorporation of an amino acid into the growing peptide chain. C-1027 is a chromoprotein antitumor antibiotic whose enediyne chro...

Discovery of novel alkylated (bis)urea and (bis)thiourea polyamine analogues with potent antimalarial activities.

A series of alkylated (bis)urea and (bis)thiourea polyamine analogues were synthesized and screened for antimalarial activity against chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. All analogues showed growth inhibitory activity against P. falciparum at less than 3 μM, with the majority having effective IC(50) values in the 100-650 nM range. Analogues arrested...

Rapid and Regioselective Hydrogenation of a,b-Unsaturated Ketones and Alkylidene Malonic Diesters Using Hantzsch Ester Catalyzed by Titanium Tetrachloride