Interesting facts from the world of organic chemistry
Alkynes and cycloalkynes:
Dynemicin A
In the early 1980s, research activities led to the isolation of completely new drugs obtained from natural sources. One such source comes from the fermentation environment of the microorganism Micromonospora chersina. A new family of substances with extraordinary effectiveness was introduced and identified. An example of such a compound with a triple bond is Dynemicin A. This substance is a particularly potent cytotoxin with LD50 values ranging from pico- to nanograms per milliliter. At these concentrations, they also act against a number of cell tumor divisions. This compound has a unique structure among naturally occurring antitumor agents, as it combines properties characteristic of both anthracycline antibiotics and the enediyne group of antibiotics.
In terms of the effect of dynemicin A, DNA damage occurs in vitro after its reductive activation. The reductive activation scheme is shown in the figure below.
Picture above: Reductive activation of dynemicin A by NADPH (nicotinamide adenine dinucleotide phosphate).
Despite its structural complexity, dynemicin A can be fully synthesized. Several possible ways of preparing dynemicin A have been developed. They differ considerably in some key steps. The reactant is also different, or reactants from which the production is based. These procedures result in a more or less substituted skeleton of dynemicin A. One possibility of total synthesis is shown schematically below.
Picture above: Scheme of a possible synthesis method of dynemicin A.
Sources:
1) MYERS A. G., M. E. FRALEY et al.: Synthesis of (+)-dynemicin A and analogs of wide structural variability: establishment of the (…).The Arnold and Mabel Beckman Laboratories of Chemical Synthesis, California Institute of Technology, Pasadena, CA 91125, USA
2) MYERS A. G., M. E. KORT et al.: Enzymatic Activation of DNA Cleavage by Dynemicin A and Synthetic Analogs. Biochemistry 1997, 36, 3903-3908.
3) MYERS A. G., N. J. TOM et al.: A Convergent Synthetic Route to (+)-Dynemicin A and Analogs of Wide Structural Variability. J. Am. Chem. Soc. 1997, 119, 6072-6094.
4) ELSOHLY A.: Dynemicin A. [12. červen 2009]. Synthesis Literacy Group, Columbia University, Chemistry. Snyder Group.