The highly enantioselective α-hydroxylation of β-keto esters using cumene hydroperoxide (CHP) as the oxidant was realized by a chiral (1S,2S)-cyclohexanediamine backbone salen-zirconium(IV) complex as the catalyst. A variety of corresponding chiral α-hydroxy β-keto esters were obtained in excellent yields (up to 99%) and enantioselectivities (up to 98% ee). The zirconium-catalyzed enantioselective α-hydroxylation of β-keto esters was scalable, and the zirconium catalyst was recyclable. The reaction can be performed in gram scale, and corresponding chiral products were acquired in 95% yield and 99% ee.

A series of cinchona-derived N-oxide asymmetric phase-transfer catalysts were synthesized and applied in the enantioselective photo-organocatalytic α-hydroxylation of β-keto esters and β-keto amides (23 examples) using molecular oxygen in excellent yields (up to 98%) and high enantioselectivities (up to 83% ee). These new catalysts could be recycled and reused six times for such a reaction with almost the original reactivity and enantioselectivity.

Methylhydrazine-induced α-hydroxylation of β-dicarbonyl compounds was achieved using O2 as the oxygen source. This reaction provides an efficient approach to enantioenriched ɑ-hydroxy β-dicarbonyl compounds, which are valuable substances and widely used in the chemical and pharmaceutical industry. A wide variety of β-keto esters could undergo this oxidation to give the corresponding products in excellent yields (up to 95%) and with good enantioselectivities (up to 85% ee). The mild reaction conditions and the use of molecular oxygen as oxidant make this protocol very environmentally friendly and practical.

Easily accessible diterpenoid alkaloid derivatives have been used as organocatalysts in the enantioselective α-chlorination of β-oxo esters. The treatment of β-oxo esters with N-chlorophthalimide (NCP) as a chlorine source under mild reaction conditions afforded the corresponding α-chlorinated β-oxo esters in excellent yields (up to 98%) and with moderate enantioselectivities (up to 68% ee) in 30 min.LappaconitineC32H44N2O8Source of chirality: natural occurrenceAbsolute configuration: (1S,4S,5S,7S,8S,9S,10S,11S,13R,14S,16S,17S)[α]D20 = +29.25 (c 0.40, MeOH)VincamineC21H26N2O3Source of chirality: natural occurrenceAbsolute configuration: (3S,14S,16S)[α]D20 = +11.5 (c 0.51, CH2Cl2)VinpocetineC21H24N2O2Source of chirality: natural occurrenceAbsolute configuration: (3S,16S)[α]D20 = +130.3 (c 0.50, CH2Cl2)CytisineC11H14N2OSource of chirality: natural occurrenceAbsolute configuration: (1R,5S)[α]D20 = −111.9 (c 0.51, MeOH)GalantamineC17H21NO3Source of chirality: natural occurrenceAbsolute configuration: (4αS,6R,8αS)[α]D20 = −117.0 (c 0.49, MeOH)SinomenineC19H23NO4Source of chirality: natural occurrenceAbsolute configuration: (9S,13R,14S)[α]D20 = −87.2 (c 0.52, MeOH)N-DeethyllappaconitineC30H40N2O8Source of chirality: lappaconitineAbsolute configuration: (1S,4S,5S,7S,8S,9S,10S,11S,13R,14S,16S,17S)[α]D20 = +42.7 (c 0.52, MeOH)N-Methyl-N-deethyllappaconitineC31H42N2O8Source of chirality: lappaconitineAbsolute configuration: (1S,4S,5S,7S,8S,9S,10S,11S,13R,14S,16S,17S)[α]D20 = +27.2 (c 0.50, MeOH)N-Benzyl-N-deethyllappaconitineC37H46N2O8Source of chirality: lappaconitineAbsolute configuration: (1S,4S,5S,7S,8S,9S,10S,11S,13R,14S,16S,17S)[α]D20 = +14.95 (c 0.50, MeOH)LappaconineC23H37NO6Source of chirality: lappaconitineAbsolute configuration: (1S,4S,5S,7S,8S,9S,10S,11R,13R,14S,16S,17S)[α]D20 = +15.45 (c 0.51, MeOH)4-BenzyloxylappaconineC30H43NO6Source of chirality: lappaconineAbsolute configuration: (1S,4S,5S,7S,8S,9S,10S,11S,13R,14S,16S,17S)[α]D20 = +2.3 (c 0.49, MeOH)8,9-(Methylenedioxy)lappaconineC24H37NO6Source of chirality: lappaconineAbsolute configuration: (1S,4S,5S,7S,8S,9S,10S,11R,13R,14S,16S,17S)[α]D20 = +13.6 (c 0.50, CHCl3)

Cinchona alkaloid-derived chiral quaternary ammonium organocatalysts were developed. The catalyst with a bulky 1-adamantoyl group at the C-9 position promoted the enantioselective α-hydroxylation of β-oxo esters and resulted in the corresponding products in 35–95% yields and 58–90% ee. The reaction was successfully scaled to a gram-quantity scale with a similar yield without loss of enantioselectivity.

A simple and stability-indicating reverse phase high performance liquid chromatographic (RP-HPLC) method was developed and validated for the determination of olanzapine (OLN) and related impurities in bulk drugs. Eight impurities were characterized respectively, and particularly a new process impurity from OLN synthesis was structurally confirmed as 1-(5-methylthionphen-2-yl)-1H-benzimidazol-2(3H)-one (Imp-7) by X-ray single crystal diffraction, MS, 1H NMR, 13C NMR and HSQC. A mechanism of formation pathway for Imp-7 was proposed. Optimum separation for OLN and eight related impurities was carried out on an Agilent Octyldecyl silica column (TC-C18, 4.6 mm × 250 mm, 5 μm) using a gradient HPLC method. The method was validated with respect to specificity, linearity, accuracy, precision, LOD and LOQ. Regression analysis showed good correlation (r2 > 0.9985) between the investigated component concentrations and their peak areas within the test ranges for OLN and eight impurities. The repeatability and intermediate precision, expressed as RSD, were less than 1.74%. The proposed stability-indicating method was suitable for routine quality control and drug analysis of OLN in bulk drugs.

The photoinduced tautomerisation of cinepazide maleate (1), an effective vasodilator widely used in clinical therapy, had been investigated. It was found that (i) the higher the concentration of cinepazide maleate (1), the more stable it was; (ii) the effect of light on the photoisomerism of cinepazide maleate (1) was obvious in a suitable wavelength (e.g., 365 nm); (iii) solvents (e.g., acetone) with carbonyl chromophore absorbing UV could inhibit the generation of cis-isomer; (iv) anthranilic acid could be used as an effective ultraviolet absorbent and (v) the cinepazide maleate (1) could be properly stored under the airtight, light-free and room temperature conditions.