Diethylstilbestrol-linked cytotoxic agents: synthesis and binding affinity for estrogen receptors.

The syntheses of diethylstilbestrol derivatives with a C4 side chain at the double bond bearing various functional and potentially alkylating groups (9-25, 38-40, 43, 44) as well as the coupling product with daunorubicin (41) are described. Derivatives with free phenolic groups show easy isomerization to (Z)-stilbenes and styrenes, which could be minimized with silyl protecting groups. Estrogen receptor binding is decreased by polar groups such as carboxylic acids (10) as well as sterically demanding substituents.

Some improvements in the synthesis of DNA of biological interest.

In a brief summary the improvements introduced during synthesis of a minigene coding for the peptide hormone angiotensin II are outlined. Furthermore some recent improvements are reviewed: comprehensive study of N-protecting groups for the heterocyclic bases, effective 3'-O-phosphorylation using phosphomonochloridates and molecular sieves, a quick and mild detritylation procedure without any depurination using ZnBr2, a convenient tritylation method using molecular sieves, introduction of a sugar spray reagent for a simpler interpretation of tlc, an improved two-step-one-flask procedure for the synthesis of fully protected triester intermediates, an introduction of new phosphate protecting groups removable by beta-elimination in homogeneous phase, synthesis of the internucleotidic phosphotriester linkage using phosphomonoazolide derivatives of deoxynucleosides, versatile methods for anchoring nucleosides to a polymer support and a computerized nucleic acid synthesizer.