Stereocontrolled Synthesis of (-)-Bactobolin A.

A stereoselective synthesis of the ribosome-binding antitumor antibiotic (-)-bactobolin A is reported. The presented approach makes effective use of (-)-quinic acid as a chiral pool starting material and substrate stereocontrol to establish the five contiguous stereocenters of (-)-bactobolin A. The key steps of the synthesis include a stereoselective vinylogous aldol reaction to introduce the unusual dichloromethyl substituent, a completely diastereoselective rhodium(II)-catalyzed C-H amination reaction to set the configuration of the axial amine, and an intramolecular alkoxycarbonylation to build the bicyclic lactone framework. The developed synthetic route was used to prepare 90 mg of (-)-bactobolin A trifluoroacetate in 10% overall yield.

Synthesis and biological assay of new 2'-deoxyuridine dimers containing a 1,2,3-triazole linker. Part I.

We describe a simple method for the synthesis of modified dinucleosides containing pyrimidine nucleoside analogues (2'-deoxyuridine, thymidine and 5-fluoro-2'-deoxyuridine). Six different dimers with a 1,2,3-triazole linkage were obtained by azide-alkyne 1,3-dipolar cycloaddition (click reaction), starting from propargylated 2'-deoxyuridine and 5'-azido-nucleoside derivatives. Their cytotoxic activity was tested in five human cancer cell lines: cervical (HeLa), high grade gliomas (U-118 MG, U-87 MG, T98G), liver (HepG2), and normal human fibroblast cell line (MRC-5) using the sulforhodamine B (SRB) assay. The experiment showed that the obtained dimers with a 1,2,3-triazole moiety were very stable compounds, also in the physiological-like media, and had no anticancer activity.