1,2‐Dithiolan‐3‐ones and Derivatives Structurally Related to Leinamycin. Synthesis and Biological Evaluation.

Abstract

Dithiole derivativesDithiole derivatives R 0175 1,2-Dithiolan-3-ones and Derivatives Structurally Related to Leinamycin. Synthesis and Biological Evaluation. -The dithiolthione oxides (II) are synthesized from the corresponding dithiolthiones (I). Compounds (I) and (II) as well as related known compounds such as (III), (VI) are tested for their activity as antineoplastic agents. -(SALVETTI, R.; MARTINETTI, G.; UBIALI, D.; PREGNOLATO*, M.; PAGANI, G.; Farmaco 58 (2003) 9, 995-998; Dip. Chim. Farm., Fac. Farm., Univ. Pavia, I-27100 Pavia, Italy; Eng.) -R. Langenstrassen 02-137

Understanding Reactivity and Assembly of Dichalcogenides: Structural, Electrostatic Potential, and Topological Analyses of 3H-1,2-Benzodithiol-3-one and Selenium Analogs

“…Note also that the oxidation of COSS in the presence of H2O2, 17 peracetic acid 18 or dimethyloxirane 19,20 selectively affords the 1-oxide (or the 1,1-dioxide known as Beaucage reagent). 21,22 3H-1,2-Benzothiaselenol-3-one (COSeS) is also known as an efficient reagent for stereospecific selenization of H-phosphates and H-phosphonothioate diesters to afford Sederivatized RNAs, DNAs and proteins, 23,24 an important issue to overcome the problems faced in their X-ray crystallographic studies.…”

“…The 1,2-dithiole derivative CSSS exhibits a reactivity comparable to COSS, with ring opening between the C=S and S−S moieties, by sp 2 nitrogen nucleophiles 28 or by active methylene compounds, 29 or with selective oxidation by H2O2 into the 1-oxide. 17 The work described here aims at rationalizing both the specific reactivity and the molecular assembly in the solid-state structures of these series of compounds, as models for many others involving a disulfide or diselenide bond. For that purpose, we have synthetized six of these eight derivatives.…”

Synthesis and Cytotoxicity of Leinamycin Antibiotic Analogues

“…On the basis of this, we thought that incorporation of the "warhead" of leinamycin into nucleosides might manage delivery to the target point of action by the formation of a base pair. Therefore, we applied our procedure to the 5′-aldehyde 16, derived from 2′,3′-di-Osilyluridine 19 (15), and through the intermediates 17, 18a, and 19a, the dithiolane-S-oxides 18b and 19b were obtained (Scheme 5).…”

“…However, the problem appears to be more complicated since Gates et al have discovered 14 an additional way for the alkylative DNA cleavage of leinamycin that is independent of thiols, and water serves as the trigger. Although the DNA splitting of several simple 1,2-dithiolan-3-one-S-oxides have been demonstrated, only one report 15 deals with their biological activity, and the investigated compounds were found to be slightly cytostatic or were inactive.…”