Elucidation of the mechanisms governing the thermal diastereomerization of bioactive chiral 1, 3, 4-thiadiazoline spiro-cyclohexyl derivatives towards their anancomeric stereoisomers. Issue 75 (27th July 2016)

• Record Type: Journal Article
• Authors: Menta, S.; Carradori, S.; Siani, G.; Secci, D.; Mannina, L.; Sobolev, A. P.; Cirilli, R.; Pierini, M.
• Is Part Of: RSC advances. Volume 6:Issue 75(2016)
• Page Start: 71262
• Page End: 71272
• Publication Date: 2016-07-27
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c6ra13727j
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Synthesis of bioactive 1, 3, 4-thiadiazoline-spiro-cyclohexyl-alkyl-substituted diastereomers by effective switching between kinetic and thermodynamic control. Abstract : The kinetics of the thermal isomerization of some diastereomers of three chiral 1, 3, 4 thiadiazoline derivatives, selected as case studies of structures resulting from mono-alkyl substitution of the anancomeric 4-acetyl-2-acetamido-1, 3, 4-thiadiazolinyl-spiro-cyclohexane (TsC ) framework, have been investigated in order to elucidate the possible mechanistic pathways and the structural factors responsible for the observed spiro-junction lability. The insertion of a methyl or a t -butyl group on the C2 or C3 position with respect to the spiro junction generates two stereogenic centres, so that two pairs of enantiomers exist. The first-order rate constants for the isomerization of the less stable enantiomers into the most stable ones have been measured in different solvents and at different temperatures through batch-wise kinetic determinations. The obtained data have been successfully rationalized by DFT calculations and Linear Solvation Energy Relationships (LSER) analyses. The achieved elucidation should make it possible to plan a more rational synthesis of this kind of pharmacologically active compounds, thus affording a practical tool that is useful for controlling the involved stereochemistry and spiro-junction lability.