Anti-tumor antibiotics synthesis

The intramolecular G-H insertion of aryldiazoacetates is a very powerful strategy for synthesizing heterocyclic rings such as dihydrobenzofurans and dihydrobenzopyrans. The first effective asymmetric copper-catalyzed C-H activation reaction was reported by the group of Sulikowski in the synthesis of the anti-tumor antibiotic FR-66979 93 (Scheme 7)123 219 The G-H insertion of the aryldiazoacetate 90 formed four diastereomeric products 91a, 91b, 92a,... 

The Pictet-Spengler reaction has also been developed on solid-support materials. This advancement provided the opportunity for the synthesis of an array of structurally diverse analogues of saframycin A, an important anti-tumor antibiotic. 

Direct reactions with DNA serve as the molecular basis for the action of several anti-tumor drugs. Cancer is primarily a disease of uncontrolled cell growth, and cell growth depends on DNA synthesis. Cancer cells are often more sensitive than normal cells to compounds that damage DNA. For example, the anti-tumor drug cisplatin reacts with guanine bases in DNA and the daunomycin antibiotics act by inserting into the DNA chain between base pairs. In either case, these biochemical events can lead to the death of a tumor cell. 

Couquelet J, Tronche P, Niviere P, Andraud G (1963) Antibiotic activity of an isomer of patulin and of a homolog. Trav Soc Pharm Montpellier 23 214-219 Holshouser MH, Loeffler LJ, Hall IH (1981) Synthesis and anti-tumor activity of a series of sulfone analogs of 1,4-naphthoquinone. J Med Chem 24 853-858... 

The field of organic synthesis has seen equally rapid advances. The emphasis has been in the development of new stereoselective methods for achieving specific synthetic transformations. The exciting synthetic approaches in the field of macrolide antibiotics, anti-tumor agents and other biologically important natural products serve to exemplify these developments. 

---