Search

A novel, I2 catalyzed regio- and stereodivergent vicinal azidohydroxylation of alkenes leading to 1,2-azidoalcohols in high yields (up to 92%) and excellent dr (up to 98%) has been developed. This unprecedented transformation employs NaN3 and DMF as N- and O-nucleophiles respectively. The role of DMF as the O-source in the reaction has been unequivocally proven by 18O labelling studies. [ABSTRACT FROM AUTHOR]

A convenient catalyst-free, three-component procedure was developed for the synthesis of tetrasubstituted pyrroles under solvent-free conditions and in green solvents glycerol, PEG-200 and water. A sequential enamine-formation, Michael addition and intramolecular cyclization of primary amines, 1,3-dicarbonyl compounds and isatin-derived Michael acceptors afforded 3-(1H-pyrrol-3-yl)indolin-2-ones in excellent yields. In this simple one-pot transformation the requirement of column chromatography purification of the products was completely avoided. Besides, the method is highly environmentally benign and atom-economical, and the only side product of this reaction was two molecules of water. A comparative study for the four developed conditions showed that the solvent-free conditions were superior regardless of the nature of the starting materials, and the green solvents were effective for alkyl and benzylamines affording higher yields compared to arylamines. The preliminary in vitro cytotoxic studies of a representative compound against Ehrlich's ascites carcinoma (EAC) tumor cells showed significant activity with a CTC50 value of 15.64 μM. [ABSTRACT FROM AUTHOR]

Voriconazole ((2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, VZL) is an antifungal drug with low aqueous solubility of 0.71 mg mL-1 and a BCS class II drug (Biopharmaceutics Classification System) of the azole family. We have prepared a nitrate salt and three cocrystals of VZL with p-hydroxybenzoic acid, p-aminobenzoic acid (both are GRAS compounds) and m-nitrobenzoic acid coformers to improve the physicochemical properties. All four multi-component crystals of voriconazole were obtained by solution crystallization as well as solid-state grinding and their structures were confirmed by X-ray diffraction, FT-IR, Raman and NMR spectroscopy, and thermal techniques. VZL--PHBA and VZL--PABA are isostructural based on XPac calculations and molecular packing arrangement. A notable result from a crystal engineering viewpoint is that the supramolecular synthon between the basic drug and the acidic coformer undergoes a switch based on the pKa of the acid. [ABSTRACT FROM AUTHOR]

A novel polymorph of N-acetyl-l-cysteine (NAC) is discovered three decades after the first report on the X-ray crystal structure of this bioactive compound. The crystal structure of the new orthorhombic polymorph (form II in the P212121 space group) is characterized by X-ray diffraction and compared to the triclinic structure of form I (NALCYS02 and NALCYS10 in the P1 space group). Both polymorphs contain a C(7) chain of COOH…O=C–CH3 hydrogen bonds, except that the COOH group is rotated by 180° in form II to make an auxiliary C–H…O interaction with the methyl group in a RSTACKABOVE2/ABOVEBELOW2/BELOW/STACK(8) ring motif. The known form I contains weak S–H…O=C–OH and N–H…S hydrogen bonds whereas the new form II has only N–H…S interactions. The conformational polymorphs of NAC were compared by Hirshfeld surface analysis (dnorm) and XPac methods, and were spectroscopically characterized by FT-IR and Raman spectroscopy. The bulk phases were distinguished by their 13C ss-NMR and powder X-ray diffraction line patterns. The two polymorphs are enantiotropically related (form I has a higher melting temperature and lower enthalpy of fusion). However, no phase transition was observed in the DSC analysis. The metastable form II converted to stable form I in solid-state grinding, a slurry medium and storage in ambient conditions for 3 months. [ABSTRACT FROM AUTHOR]

The HKR of racemic syn- or anti- alkoxy- and azido epoxides catalyzed by Co(salen) complex affords a practical access to a series of enantioenriched syn- or anti- alkoxy- and azido epoxides and the corresponding 1,2-diols. This strategy has been successfully employed in the concise, enantioselective synthesis of bioactive molecules such as (S,S)-reboxetine and (+)-epi-cytoxazone. [ABSTRACT FROM AUTHOR]

An unprecedented synthesis of novel 3-azido indoles has been developed using I2 and NaN3 in high yields and excellent regioselectivity. The reaction proceeds under metal-free conditions at room temperature. Essentially, an umpolung in reactivity at the C-3 position of indole has been achieved by the activation of indoles with I2.

A new sequential organocatalytic method for the synthesis of chiral 3-substituted (X = OH, NH2) tetrahydroquinoline derivatives (THQs) [ee up to 99%, yield up to 87%] based on α-aminooxylation or -amination followed by reductive cyclization of o-nitrohydrocinnamaldehydes has been described. This methodology has been efficiently demonstrated in the synthesis of two important bioactive molecules namely (-)-sumanirole (96% ee) and 1-[(S)-3-(dimethylamino)-3,4-dihydro-6,7-dimethoxy-quinolin-1(2H)-yl]propanone (92% ee).

The HKR of racemic anti- or syn-3-substituted epoxy esters catalyzed by a Co(III)salen complex provides ready access to the corresponding enantioenriched 3,4-disubstituted γ-butyrolactones and 3-substituted epoxy esters. This strategy has been successfully employed in the formal synthesis of biologically active 3,4-disubstituted piperidine derivatives, (-)-paroxetine and Ro 67-8867 and a natural product, (+)-eldanolide.

A new enantioselective synthesis of the anti-influenza agent (-)-oseltamivir free base (7.1% overall yield; 98% ee) and (-)-methyl 3-epi-shikimate (16% overall yield; 98% ee) has been described from readily available raw materials. Sharpless asymmetric epoxidation and diastereoselective Barbier allylation of an aldehyde are the key reactions employed in the incorporation of chirality, while the cyclohexene carboxylic ester core was constructed through a ring closing metathesis reaction.

The asymmetric dihydroxylation (AD) of o-cyano cinnamates and styrene derivatives leads to efficient construction of chiral phthalide frameworks in high optical purities. This unique reaction is characterized by unusual synergism between CN and osmate groups resulting in rate enhancement of the AD process. The method is amply demonstrated by the synthesis and the structural/stereochemical assignment of the natural products.