ChemInform Abstract: Synthesis and Radioprotective Properties of 9a-Homo-13-thiaprostanoids.

Abstract

Among bioregulators used in treatment of irradiationinduced diseases [I] a special position belongs to prostaglandins (and especially to their analogs) [2, 3]. These compounds, even taken at extremely low doses, exhibit a combination of therapeutic properties (cytoprotective activity with respect to epithelium of gastroenteric tract, endothelium of blood vessels, thrombocytes, tissue basophils, immunocompetent cells, etc.). In this connection, we may expect that prostaglandin-based radioprotectors would combine various mechanisms in protecting organism, together with low toxicity and absence of side effects. One of most justified approaches to modification of prostaglandins, which proved to provide an increase in their efficiency, selectivity, and chemical and metabolic stability, is that based on replacement of carbon by heteroatoms (N, S, O) [4] and introduction of alkyi substituents into various sites of prostanic skeleton [5]. in this work we used both methods for synthesis of previously unreported 9a-homo-13-thiaprostanoids l l a h and llla d. We have also studied radioprotective properties of these compounds and some other biological effects that can be used in prophylaxis and therapy of radiation damage. The key compounds for synthesis of these 13-thiaprostanoids are previously described vinyl analogs ofcarboxylic acid chloroanhydrides ( l a d), which were used for obtaining 13-azaprostanoids by interaction with amines [6]. Proceeding from these data and using results reported by Kirchlechner [7], we expected that interaction of chlorovinyldiketones l a d with thiols would also follow the scheme of vinyl substitution to yield 13-thiaprostanoids corresponding to structures of thiols employed. For thiophenol and thiooctanol, it was found that this reaction actually takes place upon treatmem of [a d with a two-fold excess of thiol in a THF solution in presence of a ten-fold excess of triethylamine.