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A direct visible‐light‐promoted radical‐triggered tandem cyclization of 1,7‐diene systems with cyclic sulfonium salts by using copper(I)‐based complexes as photoredox catalyst is developed. With this approach, a variety of sulfur‐containing polycyclic derivatives are prepared through alkylation/6‐exo‐trig cyclization/5‐exo‐trig cyclization of 1,7‐diene systems under mild conditions. In addition, the photoinduced copper‐catalyzed ring‐opening of cyclic sulfonium salts provides the alkyl radical intermediates, which prefers addition to the C−C double bond that connected to the aromatic ring rather than the electron‐deficient vinyl in 1,7‐dienes. Moreover, oxidation of the desired sulfur‐containing polycyclic products provides a strategy for the preparation of remote nitrogen‐fused polycyclic substituted sulfoxide or sulfone‐containing derivatives. [ABSTRACT FROM AUTHOR]

A novel strategy of visible‐light photoredox catalysis ipso‐annulation of activated alkynes with polychloroalkanes for the synthesis of 3‐polychloroalkyl spiro[4,5]trienones, which used 4‐methoxybenzenediazonium tetrafluoroborate salt as a hydrogen atom transfer reagent, is described. This polychloroalkylation/ spirocyclization of alkynes offers a widely range of 3‐polychloroalkyl‐spiro[4,5]trienone derivatives in high yields with a broad substrate scope via selective C(sp3)‐H homolytic cleavage. The results of controlled experiments showed that this method involves a radical process. The polyhaloalkyl radical species generated from intermolecular hydrogen atom transfer (HAT) between aryl radical and polychloroalkanes. [ABSTRACT FROM AUTHOR]

A simple and efficient oxidative‐promoted radical cascade annulation of ynone derivatives with ketones for the construction of a series of oxoalkyl‐substituted indenones in moderate to good yields is described. The control experiment results indicate that the oxidative acetmethylation/arylation of ynone derivatives involves a radical cascade cyclization process. This is an operationally simple and efficient protocol which will be attractive in organic synthesis chemistry. [ABSTRACT FROM AUTHOR]

A new biocatalyst PCL@UiO‐67(Zr) was successfully synthesized by immobilized lipases on metal–organic frameworks (MOFs) materials. Compare with free lipases, zirconium foundation organic framework material UiO‐67(Zr) modification on immobilized lipases Pseudomonas cepacia lipase (PCL) great boosts their enantioselectivity in the kinetic resolution racemic 4‐chloro‐mandelic acid (4‐ClMA) on the organic solvent. The acquired bio‐composite PCL@UiO‐67(Zr) was fully characterized by powder X‐ray diffraction (PXRD), Fourier transform infrared (FT‐IR) spectroscopy, N2 adsorption–desorption isotherm and aperture distribution map, and scanning electron microscopy (SEM). The catalytic performance of PCL@UiO‐67(Zr), such as temperature, reaction time, and lipase quantity, were deeply explored. The experiment results showed resolution racemic 4‐ClMA optimum conditions that 20 mmol/L of (R, S)‐4‐chloromandelic acid, 120 mmol/L vinyl acetate, 30‐mg immobilized lipases PCL@UiO‐67(Zr), 2 mL of MTBE, 500 rpm, and under the 55°C reaction 18 h. In this optimum conditions, c and eep could reach up to 47.6% and 98.7%, respectively. [ABSTRACT FROM AUTHOR]

What Is Already Known About This Subject: Mycophenolic acid (MPA) undergoes enterohepatic circulation (EHC) in the body and several population models have been proposed to describe this process using sparse data. Recent studies in Whites have found that polymorphism in UGT1A9 could partly explain the large interindividual variability associated with the pharmacokinetics of MPA., What This Study Adds: A new population pharmacokinetic model for EHC combining MPA and its main glucuronide metabolite (MPAG) simultaneously was established based on physiological aspects of biliary excretion using intensive sampling data. Pharmacokinetic profiles of MPA and MPAG with the UGT1A9 polymorphism in healthy Chinese were characterized. AIMS To establish a population pharmacokinetic model that describes enterohepatic circulation (EHC) of mycophenolic acid (MPA) based on physiological considerations and to investigate the influence of polymorphisms of UGT1A9 on the pharmacokinetics of MPA., Methods: Pharmacokinetic data were obtained from two comparative bioavailability studies of oral mycophenolic mofetil formulations. Nonlinear mixed effects modelling was employed to develop an EHC model including both MPA and its main glucuronide metabolite (MPAG) simultaneously. Demographic characteristics and UGT1A9 polymorphisms were screened as covariates., Results: In total, 590 MPA and 589 MPAG concentration-time points from 42 healthy male volunteers were employed in this study. The chain compartment model included an intestinal compartment, a gallbladder compartment, a central and a peripheral compartment for MPA and a central compartment for MPAG. The typical population clearance (CL/F) estimates with its relative standard error for MPA and MPAG were 10.2 l h(-1) (5.7%) and 1.38 l h(-1) (6.9%), respectively. The amount of MPA recycled in the body was estimated to be 29.1% of the total amount absorbed. Covariate analysis showed that body weight was positively correlated with CL/F of MPA, intercompartment CL/F of MPA and distribution volume of MPA peripheral compartment. Polymorphisms of UGT1A9 did not show any effect on the pharmacokinetics of MPA and MPAG. The model evaluation tests indicated that the proposed model can describe the pharmacokinetic profiles of MPA and MPAG in healthy Chinese subjects., Conclusions: The proposed model may provide a valuable approach for planning future pharmacokinetic-pharmacodynamic studies and for designing proper dosage regimens of MPA.