Synthesis, Chemical and Biomedical Aspects of the Use of Sulfated Chitosan.

This work is devoted to the chemical synthesis of sulfated chitosan and its experimental verification in an animal model of early atherosclerosis. The method of chitosan quaternization with sulfate-containing ingredients resulted in a product with a high content of sulfate groups. Implantation of this product into the fascial-muscular sheath of the main limb artery along the leg and thigh in rabbits led to the extraction of cholesterol from the subintimal region. Simplified methods for the chemical synthesis of quaternized sulfated chitosan and the use of these products in a model of experimental atherosclerosis made it possible to perform a comparative morphological analysis of the vascular walls of the experimental and control limbs under conditions of a long-term high-cholesterol diet. The sulfated chitosan samples after implantation were shown to change the morphological pattern of the intimal and middle membranes of the experimental limb artery. The implantation led to the degradation of soft plaques within 30 days after surgical intervention, which significantly increased collateral blood flow. The implantation of sulfated chitosan into the local area of the atherosclerotic lesions in the artery can regulate the cholesterol content in the vascular wall and destroy soft plaques in the subintimal region.

Chameleonic reactivity of vicinal diazonium salt of acetylenyl-9,10-anthraquinones: synthetic application toward two heterocyclic targets.

The nature of products in the diazotization of 1-amino-2-acetylenyl-9,10-anthraquinones strongly depends on the nature of substituents at both the alkyne and at the anthraquinone core. Donor substitution (NHAr, OH) at the fourth position stabilizes the diazonium salt at C1, decelerating electrophilic cyclization at the arylethynyl substituent at C2. This effect allows the replacement of the diazonium with azide group and subsequent closure into isoxazole ring with preservation of the alkyne. In contrast, electrophilic 5-exo-dig cyclizations to condensed pyrazoles is observed for the combination of donor substituents at the aryl alkyne moiety and an OAc substituent at C4. The latter process provides a new synthetic route to 3-ethynyl-[1,9-cd]isoxazol-6-ones that are difficult to access otherwise. DFT calculations suggest that donor substituents have only a minor effect on alkyne and diazonium polarization in the reactant but provide specific transition state stabilization by stabilizing the incipient vinyl cation. This analysis provides the first computational data on electrophilic 5-exo-dig cyclization in its parent form and the nucleophile-promoted version. This cyclization is a relatively fast but endothermic process that is rendered thermodynamically feasible by the enol-keto tautomerization with concomitant aromatization in the five-membered heteroaromatic ring. Computations suggest that the importance of nucleophilic assistance in the transition state for a relatively weak nucleophile such as water is minor because the energy gain due to the Lewis base coordination to the carbocationic center is more than compensated for by the unfavorable entropic term for the bimolecular proces.