Total Synthesis of UCS1025A

摘要

Cellular immortality is a basic defining trait of cancer.Indeed,the unlimited proliferative potential of transformed cells enables many of the most insidious characteristics of cancerous diseases.It stands to reason that disrupting the mechanism by which aberrant cells escape mortality offers a significant opportunity for chemotherapy.The primary mutation that facilitates the achievement of immortality in tumorigenic cells is upregulation of the enzyme telomerase,the ribonucleoprotein that catalyzes lengthening of telomeres.In the absence of telomerase,telomere shortening eventually leads to chromosomal instability and,hence,to the onset of senescence or apoptosis.In this way,telomeres serve as a sort of molecular clock,effectively limiting the number of times a cell may divide.It is of great interest then that telomerase,while absent in the majority of somatic tissues,is upregulated in more than 85% of cancer cell lines.Accordingly,the identification of small molecule telomerase inhibitors constitutes an appealing new chemotherapeutic strategy.