Synthesis of β-triazolyl sulfones via the reaction of vinyl sulfones with 1,2,4-triazoles under basic conditions

Russian Chemical Bulletin - A method was developed for the synthesis of β-triazolyl sulfones from vinylsulfones and 1,2,4-triazoles in the presence of sodium triazolide taken as the base. The...     

Synthesis of β-functionalized ethyl polyfluoroaryl sulfides, sulfoxides, and sulfones underlain by pentafluorobenzoic acid

The reaction of pentafluorobenzoic acid with 2-mercaptoethanol followed by modification of the reaction product by oxidationm halohydroxylation and (or) decarboxylation led to the formation of β-halo- and β-oxyethyl polyfluoroaryl sulfides, sulfoxides, and sulfones, initial compounds for the synthesis of fluorinecontaining 2,3-dihydro-1,4-benzothiazines, 2,3-dihydro-1,4-benzoxathiynes, and 2,3-dihydro-1,4-benzodithiynes and also of their S-oxides and S-dioxides based on intramolecular nucleophilic sybstitution.     

Radical-mediated thiodesulfonylation of the vinyl sulfones: access to (α-fluoro)vinyl sulfides

Radical-mediated thiodesulfonylation of the vinyl and (α-fluoro)vinyl sulfones, derived from aldehydes and ketones, with aryl thiols in organic or aqueous medium provided access to vinyl and (α-fluoro)vinyl sulfides. The vinyl sulfides were formed predominantly with E stereochemistry independent of the stereochemistry of the starting vinyl sulfones.     

Synthesis based on β-phenylethylamines. IX. Synthesis of sulfides of β-phenylethylamines and of N-benzyltetrahydroisoquinolines

New bimolecular sulfur-containing -phenylethylamines and N-benzyltetrahydroisoquinolines have been synthesized from formyl derivatives of diaryl sulfides. The possibility of using metals as catalysts for obtaining diaryl sulfides in the reaction of ortho-substituted benzaldehydes with SCl₂ has been shown for the first time.Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, Tashkent, fax (3712) 89 14 75. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 731–735, September–October, 1995. Original article submitted November 11, 1994.     

Reactions of α-fluorine-containing β-functionalized vinyl sulfides with N-nucleophiles

-Fluorine-containing -functionalized vinyl sulfides readily react with N-nucleophiles to form -fluorine-substituted products. The reactions with phenylhydrazines and amidines of acids are accompanied by cyclization at the functional group. Thermal cyclization of cyanotrifluoromethylketene N,S-acetals proceeds at the trifluoromethyl group to give substituted 3-cyanoquinolin-4-ones.     

Synthesis and chemical properties of cyclic β-keto sulfones (review)

Published data on the synthesis and chemical properties of dihydrothiophen-3(2H)-one 1,1-dioxide, dihydro-2H-thiopyran-3(4H)-one 1,1-dioxide, 1-benzothiophen-3(2H)-one 1,1-dioxide, and 1H-isothio-chromen-4(3H)-one 2,2-dioxide are reviewed. The choice of subjects was based on the presence of identical structural fragments, carbonyl, active methylene, and sulfonyl groups.     

Practical synthesis of β-acyl and β-alkoxycarbonyl heterocyclic sulfones

A short and efficient synthesis for β-acyl and β-alkoxycarbonyl heterocyclic sulfones containing benzothiazol (BT) and phenyltetrazol (PT) heterocyclic core is presented here. The method seems to be general and provides the desired C-nucleophiles in very good to excellent yields from readily available starting materials.     

Catalytic asymmetric synthesis of γ-substituted vinyl sulfones

A fast new entry for the stereoselective construction of γ-substituted vinyl sulfones is presented. The key for success is the use of a readily available chiral secondary amine catalyst that allows the use of base-sensitive β-nitroethyl sulfones as masked β-sulfonyl vinyl anions in conjugate additions. The method performed in a three-step one-pot operation gives access to a great variety of vinyl sulfones in good yields and with excellent enantioselectivities. The method has also been extended to other relatively base-sensitive β-electron-withdrawing-substituted nitroalkanes to afford products with manifold functionality, providing a quick entry to very attractive synthetic intermediates for organic synthesis.     

Synthesis of novel β-amino alcohols and their application in the catalytic asymmetric sulfoxidation of sulfides

Novel chiral norephedrine-based β-amino alcohol ligands containing a thiophene ring were prepared from norephedrine and substituted furan carbaldehydes (methyl- or ethyl-substituted) and used in combination with VO(acac)₂ for the asymmetric oxidation of aryl methyl sulfides using H₂O₂ as an oxidant. Amino alcohol derived Schiff bases 4,5a–b gave higher enantiomeric excesses than amino alcohol-derived reduced Schiff based ligands 6,7a–b. Of these chiral ligands, (1S,2R)-5b and (1S,2R)-7b gave high yields (90%) with moderate to high enantioselectivities (78%, 96% ee, respectively). The oxidation of other aryl methyl sulfides with (1S,2R)-5b and (1S,2R)-7b as ligands afforded the corresponding sulfoxides in 60–89% yields and with 92–99% ee.     

Synthesis and structures of α-lithiated vinyl ethers

The structures of α-lithiated vinyl ethers were explored on the basis of a combined computational and NMR study. Calculations (M06/6-31 + G(d)) on free energies of aggregate formation for a series of α-lithiated vinyl ethers indicated that the tetramer is generated preferentially in both the gas phase and THF solution, except for cyclohexylidene derivatives. (1-(Methoxymethoxy)vinyl)lithium, (2,2-difluoro-1-(methoxymethoxy)vinyl)lithium, and (1-butoxyvinyl)lithium were prepared in NMR tubes by the deprotonation of alkyl/alkoxylalkyl vinyl ethers or by the transmetalation of tin compounds. The NMR spectra of these lithium species in THF solution showed that in each species one aggregate is primarily present at 173 K, which is consistent with the preference of the tetramer.     

Discovery of a potent and highly β1 specific proteasome inhibitor from a focused library of urea-containing peptide vinyl sulfones and peptide epoxyketones

Syringolins, a class of natural products, potently and selectively inhibit the proteasome and show promising antitumour activity. To gain insight in the mode of action of syringolins, the ureido structural element present in syringolins is incorporated in oligopeptide vinyl sulfones and peptide epoxyketones yielding a focused library of potent new proteasome inhibitors. The distance of the ureido linkage with respect to the electrophilic trap strongly influences subunit selectivity within the proteasome. Compounds 13 and 15 are β5 selective and their potency exceeds that of syringolin A. In contrast, 5 may well be the most potent β1 selective compound active in living cells reported to date.     

Improved Synthesis of Icaritin and Total Synthesis of β-Anhydroicaritin

Natural products icaritin and β-anhydroicaritin with P-glycoprotein(P-gp) inhibitory activities were ciently synthesized in nine steps from commercially available phloroglucinol. A modified Algar-Flynn-Oyamada cyclization and relay Claisen-Cope rearrangement were employed in this concise route. Oiir synthesis offers opportunities to synthesize various icariin analogues for biological and pharmacological investigations.     

Practical and stereoselective synthesis of β-amino sulfones from alkyl phenyl sulfones and N-(tert-butylsulfinyl) aldimines

A practical and straightforward approach for the highly stereoselective synthesis of β-amino sulfones was developed. With lithium bis(trimethylsilyl)amide as the base, the corresponding sulfone-stabilized carbanion derived from alkylphenyl sulfone can be transferred to N-(tert-butylsulfinyl) aldimines in excellent yields and with high diastereoselectivity.     

Chlorolysis of β-functionalized alkyl polyfluoroalkenyl sulfides

Chlorolysis of -functionalized alkyl polyfluoroalkenyl sulfides giving rise to -functionalized polyfluoroalkenesulfenyl chlorides was examined. -Cyano-containing sulfenyl chlorides underwent intramolecular cyclization at the nitrile group to form substituted isothiazoles.     

Synthesis and crystal structure of β-hexanitrohexaazaisowurtzitane

A polycyclic caged compound with high strain—hexanitrohexaazaisowurtzitane (HNIW)—has been synthesized via a three-step reaction: condensation, hydrogenolysis debenzylation and nitrolysis, starting with benzylamine and glyoxal. HNIW is the most powerful high energy density compound (HEDC) ever tested. β-HNIW possesses a caged structure consisting of two five-membered rings and one six-membered ring with a nitro group attached to each of the six bridging nitrogens. The nitro group lies basically within a plane. The lengths of C—C bonds of β-HNIW range from 0. 156 nm to 0.159 nm, 0.002–0.005 nm longer than the sp³ C-C bond. The β-HNIW’s crystal belongs to orthorhombic system and space groupPca2₁ with parameters:a = 0.9670 (2),b = 1.1616 (2),c = 1.3032 (3) nm;V = 1.4638(5) nm³,Z = 4; D_c = 1.989 g/cm³ and D_m = 1.982 g/cm³. Project supported by the Advanced Research Funds (12060451867) from the Commission of Science and Technology for National Defence.     

Synthesis and crystal structure of β-hexanitrohexaazaisowurtzitane

A polycyclic caged compound with high strain——hexanitrohexaazaisowurtzitane (HNIW)——has been synthesized via a three-step reaction: condensation, hydrogenolysis debenzylation and nitrolysis, starting with benzylmine and glyoxal. HNIW is the most powerful high energy density compound (HEDC) ever tested. β-HNIW possesses a caged structure consisting of two five-membered rings and one six-membered ring with a nitro group attached to each of the six bridging nitrogens. The nitro group lies basically within a plane. The lengths of C--C bonds of β-HNIW range from 0.156 nm to 0.159 nm, 0.002--0.005 nm longer than the sp~3 C-C bond. The β-HNIW's crystal belongs to orthorhombic system and space group Pca2_1 with parameters: a=0.9670 (2), b=1.1616 (2), c=1.3032 (3) nm; V=1.4638(5) nm~3, Z=4; D_c=1.989 g/cm~3 and D_m=1.982 g/cm~3.     

Synthesis and biology of N-thiolated β-lactams

N-Thiolated β-lactams are an interesting new family of bioactive agents having antibacterial, antifungal, and anticancer capabilities. Our interest in these β-lactams stems from their highly unusual structure–activity profiles and selectivity toward only a few genera of pathogenic bacteria, including Staphylococcus aureus, Bacillus anthracis, and Micrococcus. Here, we provide a complete outline on our work in the discovery and ongoing development of these compounds, starting from our initial, unexpected finding of antimicrobial activity for one of the lead compounds, to a more complete understanding of their chemical and biological mode of action and potential utility as antibacterial compounds.