Fused Isothiazole S‐Oxide Systems from Cycloaddition Reactions of N‐Benzylisothiazol‐3‐amine 1‐Oxide

Abstract

The racemic N-benzylisothiazol-3-amine 1-oxide (2) was demonstrated to be an efficient partner in Diels -Alder reactions (Schemes 2 -4) and a good dipolarophile in 1,3-dipolar cycloaddition reactions with nitrile oxides (Scheme 5). Polycyclic isothiazole S-oxides with different substitution patterns were obtained from 2 in good yield and in a fully regioselective way. Improved diastereoselection was observed performing the Diels -Alder or 1,3-dipolar cycloaddition reactions in H 2 O.Introduction. -Recently, we described the synthesis of chiral racemic isothiazolamine S-oxides A, starting from the corresponding isothiazolamines 1, and some preliminary studies on their reactivity toward S-nucleophiles which demonstrated the ability of the sulfoxide moiety to direct the addition affording the corresponding 5-(aryl-and alkylthio) derivatives in a fully diastereoselective way (Scheme 1) [1]. The availability of these new S-oxides A prompted us to continue our research on their reactivity. In particular, we concentrated our attention on the aptitude of this system to act as an effective reaction partner in cycloaddition reactions which would allow the preparation of fused isothiazole S-oxide derivatives of both chemical and pharmacological interest. In fact, cycloaddition reactions appeared to be a very versatile tool to obtain new classes of isothiazoles or fused isothiazole systems or new or known heterocycles by the transformation of the primary cycloadducts similarly to the transformations described for the corresponding S,S-dioxides [2 -6]. The exploitation of the sulfoxide system could be considered of large interest due to the significant stereodifferentiating ability of the sulfinyl function [7]. Moreover, taking into account the general interest in environmental contamination, efforts were devoted in this work to develop cycloaddition processes with reduced environmental impact.

Synthesis, Molecular Characterization and Preliminary Antioxidant Activity Evaluation of Quercetin Fatty Esters

“…NMR computations were performed on the most stable conformations at the mPW1B95/TZVP level. As in other works this basis set provided the best results in terms of accuracy/computation time [26,27]. The absolute shieldings of penta, tetra and triesters were calculated using the GIAO method [28,29].…”

“…Quantum chemical NMR calculation were then performed on 3,5,7,3 0 ,4 0 -pentaester, 3,7,3 0 ,4 0 -tetraester, 3,7,3 0 triester, 3,7,4 0 -triester and 7,3,4 0 -triester to assist the experimental structural assignment. Indeed, this technique was successfully used by our group to solve similar questions [26,27]. Calculations on long and highly flexible fatty acid quercetin esters could not be performed, as the huge conformational flexibility would have made both of the calculations too expensive, in terms of CPU time, as well as the interpretation of results more difficult, due to the large noise introduced by the side-chain signals.…”

Synthesis and Biological Evaluation of New Natural Phenolic (2E,4E,6E)‐Octa‐2,4,6‐trienoic Esters

“…Since the unequivocal assignment of the structure of 6a and 6b was not possible, experiments were integrated by quantum chemical (QM) calculations. Indeed, NMR parameters of organic molecules can be accurately computed by QM calculation, and the comparison of theoretical and experimental chemical shifts can allow a complete structural attribution to non‐trivial structures like tautomers or regioisomers . In our case, the comparison of these data with the experimental NMR shifts ( Table ) suggests that the major compound is that in which the hydrolysis undergone at the HO–C(4), thus giving caffeic monoester at position C(3).…”