Zhersh S. Derivatives of conformationally restricted heteroaliphatic amino sulfonic acids

The thesis is related to the synthesis of derivatives of conformationally restricted amino sulfonic acids and investigation of conformational behaviour of model peptidomimetics containing the cyclic aminosulfonic acids residues. An approach to the synthesis of conformationally restricted saturated heterocyclic sulfochlorides was developed. A mini-library of saturated heterocyclic sulfochlorides was designed and synthesized. The library consisted of 9 members which are derivatives of azetidine, pyrrolidine and piperidine. The title compounds were prepared in 19–88% total yields at multigram scale starting from the corresponding Cbz-protected amino alcohols. A convenient method for preparation of 1-(pyrrolidin-2-yl)-1H-azoles, 1-(piperidin-2-yl)-1H-azoles, and 1-(piperidin-3-yl)-1H-1,2,4-triazoles by alkylation of azoles (i. e. pyrazoles, imidazoles, and triazoles) with N-Cbz-prolinol mesylate or its analogues and subsequent deprotection was developed. The two-step sequence allowed for the obtaining of the title compounds in 16–65% yields. The utility of the procedure was demonstrated by multigram preparation of a 15-member building block mini-library. These building blocks perfectly fit the definition of low-molecular-weight hydrophilic three-dimensional templates, which leave much room for the lead-oriented synthesis of the compound libraries.