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[en] Data on applications of the most important rearrangements of sulfoxides and sulfones to stereoselective total syntheses of natural compounds are systematised. The bibliography includes 175 references.
[en] Data on the use of sulfones and sulfoxides in total stereo-, regio- and enantioselective syntheses of natural compounds published over the last 15-20 years are discussed and classified into the most important types of reactions. The bibliography includes 420 references.
[en] A new synthetic approach to α-keto cyano-phosphorane ylides from olefins utilizing a novel xanthate reagent 6 has been developed. There are several advantages expected from this new approach e. g., easy preparation of 6 from commercial reagents in excellent yield, mild reaction conditions, good to excellent overall yields. Currently we are doing additional experiments to determine the scope and limitation of this new approach, and those results will be reported in due course. We have developed new synthetic approaches to α-keto cyanophosphorane ylides from readily available chemicals using specially designed new reagents to overcome such limitation. For example, α-keto cyanophosphorane ylides have been prepared from carbonyl compounds using a new Horner-Wadsworth-Emmons (HWE) reagent, from alkyl bromides using a new phenylsulfinyl reagent through alkylation-sulfoxide elimination sequence, and from alkyl halides using a new phenylsulfonyl reagent via sequential alkylation-reductive desulfonylation protocol
[en] The dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is believed to play a central role in Parkinson's disease neurodegeneration by stabilizing potentially toxic oligomers of the presynaptic protein α-Synuclein (aSyn). Besides the formation of covalent DOPAL-Lys adducts, DOPAL promotes the oxidation of Met residues of aSyn, which is also a common oxidative post-translational modification found in the protein in vivo. Herein we set out to address the role of Met residues on the oligomerization and neurotoxic properties of DOPAL-modified aSyn. Our data indicate that DOPAL promotes the formation of two distinct types of aSyn oligomers: large and small (dimer and trimers) oligomers, which seem to be generated by independent mechanisms and cannot be interconverted by using denaturing agents. Interestingly, H2O2-treated aSyn monomer, which exhibits all-four Met residues oxidized to Met-sulfoxide, exhibited a reduced ability to form large oligomers upon treatment with DOPAL, with no effect on the population of small oligomers. In this context, triple Met-Val mutant M5V/M116V/M127V exhibited an increased population of large aSyn-DOPAL oligomers in comparison with the wild-type protein. Interestingly, the stabilization of large rather than small oligomers seems to be associated with an enhanced toxicity of DOPAL-aSyn adducts. Collectively, these findings indicate that Met residues may play an important role in modulating both the oligomerization and the neurotoxic properties of DOPAL-derived aSyn species.
[en] Kinetic studies of the reactions of ο,ο-diphenyl Z-S-aryl phosphorothioates with X-benzylamines have been carried out in dimethyl sulfoxide at 55.0 .deg. C. The Hammett (log k_2 vs σ_X) and Bronsted [log k_2 vs pK_a(X)] plots for substituent X variations in the nucleophiles are biphasic concave downwards with a maximum point at X = H, and the unusual positive ρ_X and negative β_X values are obtained for the strongly basic benzylamines. The sign of the cross-interaction constant (ρ_X_Z) is negative for both the strongly and weakly basic nucleophiles. Greater magnitude of ρ_X_Z value is observed with the weakly basic nucleophiles (ρ_X_Z = -2.35) compared to with the strongly basic nucleophiles (ρ_X_Z = -0.03). The deuterium kinetic isotope effects (k_H/k_D) involving deuterated benzylamines [XC_6H_4CH_2ND_2] are primary normal (k_H/k_D > 1). The proposed mechanism is a concerted S_N2 involving a frontside nucleophilic attack with a hydrogen bonded, four-center-type transition state for both the strongly and weakly basic nucleophiles. The unusual positive ρ_X and negative β_X values with the strongly basic benzylamines are rationalized by through-space interaction between the π-clouds of the electron-rich phenyl ring of benzylamine and the phenyl ring of the leaving group thiophenoxide
[en] Rearrangements of 1,3-oxathiolane sulfoxides 8 and 9 in the presence of base are described from a mechanistic viewpoint of sigmatropic and elimination reactions. In the presence of triethylamine the (Z)- sulfoxide 8 gave the corresponding thiolsulfinate 10 by way of dimerization of the sulfenic acid intermediate 2 at room temperature while the (E)-sulfoxide 9 was recovered even after refluxing in ethyl acetate by the reversal of the [2,3]-sigmatropic rearrangement of the sulfenic acid 4. Triethylamine promoted the developing charge separation in the transition state of the sigmatropic rearrangement of the (Z)-sulfoxide 8 to facilitate the ring opening to the sulfenic acid 2. The reason for more facile ring opening of the (Z)-sulfoxide 8 in comparison with the corresponding (E)-sulfoxide 9 is attributable to the differences in the reactivity of the hydrogen adjacent to the carbonyl group. Triethylamine was not strong base to deprotonate the carbonyl-activated methylene hydrogen of the (E)-sulfoxide 9 but enough to catalyze the sigmatropic process of the sulfoxides. The sulfenic acid 2 dimerized to the thiolsulfinate 10 while the sulfenic acid 4 proceeded the sigmatropic ring closure. In the presence of strong base such as potassium hydroxide, the elimination reaction was predominant over the sigmatropic rearrangement. In this reaction condition, both sulfoxides 8a and 9a gave a mixture of the disulfide 12, the isomeric disulfide 14, and the sulfinic acid 13. Under the strong alkaline condition an elimination of activated hydrogen from the carbon adjacent to the carbonyl group to furnish the sulfenic acid 2a and the isomeric sulfenic acid 18. The formation of the transient intermediate in the reaction was proven by isolation of the isomeric disulfide 14. The reactive entity was regarded as the sulfenic acid rather than sulfenate anion under these reaction conditions
[en] Second-order rate constants (kN) have been determined spectrophotometrically for reactions of 2,4- dintrophenyl 2-furoate (2) with a series of alicyclic secondary amines in 80 mol % H2O/20 mol % dimethyl sulfoxide (DMSO) at 25.0 .deg. C. The furoate 2 is more reactive than 2,4-dintrophenyl benzoate (1) toward all the amines studied. The higher acidity of 2-furoic acid (pKa = 3.16) compared with benzoic acid (pKa = 4.20) has been suggested to be responsible for the reactivity order, at least in part. The Brφnsted-type plots for the reactions of 1 and 2 are curved downwardly, indicating that the aminolyses of both 1 and 2 proceed through a zwitterionic tetrahedral intermediate (T±) with a change in the rate-determining step on changing the amine basicity. Dissection of the kN values into their microscopic rate constants has revealed that the pKa .deg. and k2/k-1 ratios for the reactions of 1 and 2 are identical, indicating that the nature of the nonleaving group (i.e., benzoyl and 2-furoyl) does not affect the reaction mechanism. The k1 values have been found to be larger for the reactions of 2 than for those of 1, which is fully responsible for the fact that the former is more reactive than the latter
[en] Nucleophilic substitution reactions of 5-XC4H2 (S)C(O)OC6H3 -2-Y-4-NO2 (1) promoted by 4-Z-C6H4O −/4-Z-C6H4OH in 20 mol % dimethyl sulfoxide (DMSO)(aq) have been studied kinetically. The reactions exhibited second-order kinetics with βacyl = −2.52 to −2.83, ρ(x) = 2.81–3.16, βnuc = 0.88–0.04 and βlg = −0.94, respectively. The results have been interpreted with an addition–elimination mechanism in which the nucleophilic attack occurs in the rate-determining step. Comparison with existing data reveals that the rate-determining step changes from the second to the first step by the change in the nucleophile from R2NH/R2NH2 + to 4-Z-C6H4O −/4-Z-C6H4OH