Synthesis of protected amino thymidines and new thiol derivatives of the vascular targeting agent combretastatin A-4.

Protected amino thymidines were synthesized as part of a project aimed at developing reagents for the site-specific, sequence selective DNA cleavage. Modified DNA oligonucleotides have the capacity to behave like artificial restriction enzymes in addition to being agents for the targeted scission of DNA and RNA in antiviral and gene therapy. Sulfur-containing analogues of the vascular targeting agent (VTA) Combretastatin A4 (CA4) were also synthesized. Vascular targeting agents are a class of anticancer compounds made to target and restrict tumor neovasculature. Disruption of these new tumor-associated capillaries prevents the blood flow necessary to feed the tumor, resulting in tumor cell starvation, the build-up of toxins, and massive necrotic cell death. One of the best characterized small molecule vascular targeting agents is Combretastatin A-4 (CA4), which is currently in Phase II clinical trials.