Zarovna I. Sulfolane-containing aminoalcohols and sulfonamides. Synthesis and properties

The thesis is devoted to the synthesis of a number of sulfolane-containing aminoalcohols and hydroxysulfonamides with cage fragments as well as sulfolane-containing amines and sulfonyl chlorides, tetrahydrothiophene-1,1-dioxides annelated with oxazoline, oxazolidine, oxazolidinone, morfolinone cycles. Using quantum chemical calculations, we have found the main factors that influence aminolysis of 3,4-epoxysulfolane with ammonia or primary amines. We have also studied the reaction of trans- and cis-4-amino-3-hydroxysulfolanes with electrophilic reagents and compared their ability for cyclization. Oxazolines were synthetized by cyclization of cis-N-monoacylated derivatives. Reaction of cis-4-amino-3-hydroxysulfolane with triphosgene furnishes oxazolidinone and with dimethyl acetylenedicarboxylate a morpholinone. In both cases, corresponding trans-isomers did not give desired heterocycles since such orientation of substituents prevents cyclization. cis-Aminoalcohols undergo heterocyclization with formaldehyde to form oxazolidines, however, under the same conditions, trans isomers lead to less strained dioxazepines or dioxazecines. We have also studied tautomeric transformations of sulfolane-containing imines with aromatic substituents. According to the results of in silico, in vitro and in vivo studies of pharmacological activity in the group of synthesized compounds, potential CK2 and FGFR-1 kinase inhibitors, compounds with anticancer, antimicrobial and fungal, neurotrophic activity were found.