I2-Mediated Site-Selective C-H Functionalization: Access to p-Amino-Substituted Unsymmetrical Benzils and Quinoxalines from Sulfoxonium Ylides.

An I2-mediated approach for selective C-H functionalization of unprotected aniline derivatives for synthesizing benzils and quinoxaline derivatives from sulfoxonium ylides has been described. Aniline derivatives and sulfoxonium ylides ornamented with different functional groups showed good compatibility. They afforded the corresponding products with moderate to high yields via a mild and simple procedure. Finally, we validated the practicality of this method by scaling up the reaction and further conversion of the synthesized derivatives into other valuable molecules.

Straightforward access to α-carbonyloxy esters and ß-keto thioethers from aryldiazoacetates.

A metal- and additive-free approach has been described for synthesizing α-carbonyloxy esters and ß-keto thioethers from readily available aryldiazoacetates with carboxylic acids and thiol derivatives, respectively. α-Carbonyloxy esters and ß-keto thioether derivatives were synthesized in good to high yields from aryldiazoacetates, carboxylic acids, and thiol derivatives decorated with various functional groups. Finally, the potential of the new approach is demonstrated through its application in gram-scale reactions and the synthesis of a few bioactive molecules.

Proline-catalyzed synthesis of α-substituted (E)-α,ß-unsaturated aldehydes from epoxides.

A novel, simple and metal-free tandem approach for synthesizing α-substituted (E)-α,ß-unsaturated aldehyde derivatives through acid-catalyzed epoxide rearrangement and organocatalyzed aldol condensation processes has been described. This transformation has a broad substrate scope under mild conditions, including epoxides and aldehydes containing diverse functional groups, resulting in moderate to high yields of the desired products. Eventually, large-scale reactions and the synthesis of some bioactive molecules are used to demonstrate the potential applicability of the developed method.

Metal-free synthesis of α-acyloxy ketones from carboxylic acids and sulfoxonium ylides.

A straightforward, catalyst- and additive-free approach has been described for synthesizing α-acyloxy ketones from ß-ketosulfoxonium ylides and carboxylic acids. Moderate to high yields of α-acyloxy ketones were produced using sulfoxonium ylides and carboxylic acids adorned with various functional groups. Eventually, the applicability of this approach has been shown via a large-scale reaction and transforming the synthesized α-acyloxy ketone derivatives into other valuable compounds.

Straightforward access to α-thiocyanoketones and thiazoles from sulfoxonium ylides.

Efficient, versatile, and metal-free strategies for synthesizing α-thiocyanoketones and thiazoles from ß-ketosulfoxonium ylides and ammonium thiocyanate have been described. Due to its simplicity, benign reaction conditions, excellent chemoselectivity, and high yield, this method represents a unique approach for divergent synthesis. Finally, the potential value of the developed methods is demonstrated via large-scale reactions and synthesis of Fanetizole, an anti-inflammatory drug.

Elemental Sulfur-Mediated Synthesis of Quinoxalines from Sulfoxonium Ylides.

A novel straightforward and catalyst-free approach for synthesizing quinoxaline derivatives from sulfoxonium ylides and o-phenylenediamines mediated by elemental sulfur has been described. Due to the simple and mild reaction conditions, the sulfoxonium ylides and o-phenylenediamines decorated with different functional groups furnished moderate to high yields of quinoxaline derivatives and were well tolerated. Finally, large-scale reactions, the synthesis of pyrazines, and some bioactive compounds are used to illustrate the potential utility of the developed approach.

Multicomponent Reaction of CS2, Amines, and Sulfoxonium Ylides in Water: Straightforward Access to ß-Keto Dithiocarbamates, Thiazolidine-2-thiones, and Thiazole-2-thiones.

Simple, versatile, and catalyst-free synthetic methods for ß-keto dithiocarbamates, thiazolidine-2-thiones, and thiazole-2-thiones via the multicomponent reaction of CS2, amines, and sulfoxonium ylides have been described. The ß-keto sulfoxonium ylides furnished ß-keto dithiocarbamates in the presence of CS2 and secondary amines, whereas primary amines afforded thiazolidine-2-thiones or thiazole-2-thiones after dehydration in an acidic environment. With simple procedures, the reaction has a wide substrate scope and excellent functional group tolerance.

Synthesis of α-Carbonyl-α'-amide Sulfoxonium Ylides from Isocyanates with Complete Atom Economy.

An efficient catalyst- and additive-free facile synthesis of α-carbonyl-α'-amide sulfoxonium ylides from isocyanates and ß-ketosulfoxonium ylides with complete atom economy has been described. The ß-ketosulfoxonium ylides and isocyanates adorned with various functional groups were well-tolerated and afforded moderate to high yields of the α-carbonyl-α'-amide sulfoxonium ylide derivatives. Finally, using large-scale reactions and converting the synthesized ylides into other valuable compounds, we demonstrated the practicality of this synthetic method.

Organocatalyzed epoxidation in the total synthesis of (-)-trans-, (+)-trans- and (+)-cis-disparlures.

A simple, flexible and efficient organocatalyzed synthetic approach for the synthesis of (-)-trans-, (+)-trans- and (+)-cis-disparlures has been described. The pivotal reaction sequence comprises organocatalyzed asymmetric Jørgensen epoxidation, Wittig olefination, migration of epoxide and Mitsunobu inversion reaction. Excellent enantiomeric purity (≥99%) was achieved during the synthesis of disparlure enantiomers by the Jørgensen epoxidation key step.

Catalyst- and additive-free syntheses of rhodanine and S-alkyl dithiocarbamate derivatives from sulfoxonium ylides.

An efficient catalyst- and additive-free facile access to rhodanine and S-alkyl dithiocarbamate derivatives via multi-component reaction of amines, CS2 and α-ester sulfoxonium ylides in methanol has been described. The new synthetic methods offer excellent synthetic prospects for several functionalized rhodanines and S-alkyl dithiocarbamates with simple operational procedures.

Metal-Free Syntheses of α-Ketothioamide and α-Ketoamide Derivatives from Sulfoxonium Ylides.

An efficient base, additive and metal-free synthetic methods for α-ketothioamide and α-ketoamide derivatives from readily available sulfoxonium ylides have been described. Sulfoxonium ylides with primary or secondary amines afforded α-ketothioamides in the presence of elemental sulfur, whereas α-ketoamides were produced when I2 and TBHP were present. The reaction proceeded well at room temperature and generated the corresponding molecules in good to excellent yields. The reaction can be scaled-up and tolerated by a range of functional groups with simple operational procedures.

Organocatalyzed Protecting-Group-Free Total Synthesis of (S,S)- and (S,R)-Reboxetine, an Antidepressant Drug.

An efficient, simple, and concise organocatalyzed protecting-group-free synthetic approach to the stereoisomers of the antidepressant drug reboxetine and its implementation toward the asymmetric synthesis of (S,S)-reboxetine and (S,R)-reboxetine from commercially available trans-cinnamaldehyde are described. The synthesis features organocatalytic Jørgensen asymmetric epoxidation, epoxide migration, and Mitsunobu inversion as key steps.

Synthesis of rhein and diacerein: a chemoenzymatic approach using anthrol reductase of Talaromyces islandicus.

Herein, we report two methods for the synthesis of the osteoarthritis drug rhein and its prodrug diacerein using a chemoenzymatic approach. The strategy relies on the use of an NADPH-dependent anthrol reductase of Talaromyces islandicus (ARti-2), which mediates the regioselective and reductive deoxygenation of anthraquinones. The work further implies similar biosynthesis of rhein in fungi.

An efficient enantioselective approach to multifunctionalized γ-butyrolactone: concise synthesis of (+)-nephrosteranic acid.

A short, efficient and novel approach for multifunctionalized γ-butyrolactone paraconic acids and its application to the total synthesis of (+)-nephrosteranic acid from readily available PMB (R)-glycidyl ether as a starting material are described. Key transformations include asymmetric Michael addition catalyzed by chiral diphenylprolinol silyl ether and stereoselective α-methylation.

Hetero-Polysaccharides Secreted from Dunaliella salina Exhibit Immunomodulatory Activity Against Peripheral Blood Mononuclear Cells and RAW 264.7 Macrophages.

Several species of microalgae have been known to produce exopolysaccharides (EPS) with potential immune activity. In the present investigation, ethyl acetate fraction of crude EPS secreted by Dunaliella salina was explored for immunomodulatory activity against peripheral blood mononuclear cells (PBMC) and RAW 264.7 macrophages. Effect of EPS on cell growth and cytokines production were measured using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and ELISA respectively. Griess reagent was used for measuring the nitric oxide production in RAW 264.7 macrophages. FTIR analysis and mass spectroscopy were carried out for the characterization. Ethyl acetate fraction exhibited dose dependent increase in proliferative index and cytokines production (IFN-γ, TNF-α, TGF-ß). At low concentration (250 and 500 µg/mL), it showed growth inhibition and at higher concentration (1000 and 1500 µg/mL), it enhanced the cell growth. Interestingly, the pronounced increased TNF-α production was observed in ethyl acetate fraction treated PBMC cells at higher concentration (750 and 1000 µg/mL) indicating the immunostimulatory effect. In RAW cells, concentration dependent diminished cell growth (IC50 = 691 µg/mL) and nitric oxide production (IC50 = 630 µg/mL) was observed. FTIR analysis showed the presence of polysaccharides due to the detection of hydroxyl (-OH), Carbonyl (C-O) and alkyl (C-H) groups. Mass spectroscopy results revealed ethyl acetate fraction as penta-saccharide (m/z = 887.56 and 886.54) which are confirmed to be hetero-polysaccharides consisting of hexoses and pentoses along with association of ions. These results suggest that penta-saccharide (ethyl acetate fraction) isolated from D. salina may have the potential to be used for therapeutic purpose as immunomodulatory agent.

An AcOH-mediated metal free approach towards the synthesis of bis-carbolines and imidazopyridoindole derivatives and assessment of their photophysical properties.

An AcOH-mediated concise, atom-economical and environmentally sustainable tandem strategy has been formulated to access highly fluorescent (ΦF up to 40%) N-fused bis-carbolines, imidazopyrido[3,4-b]indoles and imidazo[1,5-a]pyridines via the formation of three C-N bonds in a single operation. The multicomponent character of the reaction, easy to execute reaction conditions, simple purification procedure and excellent light emitting properties of the product afforded thereof provide a huge scope.

Total synthesis of haliclamide.

A stereoselective approach for the synthesis of haliclamide 1, a marine natural product, has been developed. The notable features of our synthesis include MacMillan cross aldol, Mitsunobu inversion, Yamaguchi-Hirao alkylation, Steglich esterification and macrolactamization reactions and the Corey-Fuchs protocol as the key steps.

An enantioselective approach to functionalized amino acids: total synthesis of antiepileptic drug (R)-lacosamide.

A short and highly efficient synthetic approach to enantiopure functionalized amino acids (FAAs) 1 skeleton from racemic butadiene monoepoxide as a starting material and its application to the total synthesis of an antiepileptic drug (R)-lacosamide 2 are described. The synthesis utilizes the palladium catalyzed Trost's Dynamic Kinetic Asymmetric Transformation (DYKAT) as key step.