An asymmetric aza-Diels-Alder and O-Michael addition sequence has been developed to construct chiral hy- dropyrano[2,3-b]pyridine derivatives with good yields and excellent stereoselectivity, by starting with N-Ts-l-a...An asymmetric aza-Diels-Alder and O-Michael addition sequence has been developed to construct chiral hy- dropyrano[2,3-b]pyridine derivatives with good yields and excellent stereoselectivity, by starting with N-Ts-l-aza- 1,3-butadienes and aliphatic aldehydes tethered to an α,β-unsaturated ketone motif. A tandem O-Michael addition reaction was completed via acid catalysis.展开更多
Dihydrofolate reductase(DHFR),a housekeeping enzyme in primary metabolism,has been extensively studied as a model of acid-base catalysis and a clinic drug target.Herein,we investigated the enzymology of a DHFR-like pr...Dihydrofolate reductase(DHFR),a housekeeping enzyme in primary metabolism,has been extensively studied as a model of acid-base catalysis and a clinic drug target.Herein,we investigated the enzymology of a DHFR-like protein SacH in safracin(SAC)biosynthesis,which reductively inactivates hemiaminal pharmacophore-containing biosynthetic intermediates and antibiotics for self-resistance.Furthermore,based on the crystal structure of SacH−NADPH−SAC-A ternary complexes and mutagenesis,we proposed a catalytic mechanism that is distinct from the previously characterized short-chain dehydrogenases/reductases-mediated inactivation of hemiaminal pharmacophore.These findings expand the functions of DHFR family proteins,reveal that the common reaction can be catalyzed by distinct family of enzymes,and imply the possibility for the discovery of novel antibiotics with hemiaminal pharmacophore.展开更多
The reaction of carbonyl-to-imine/hemiaminal conversion in the atmospheric aqueous phase is a critical pathway to produce the light-absorbing N-containing secondary organic compounds(SOC).The formation mechanism of th...The reaction of carbonyl-to-imine/hemiaminal conversion in the atmospheric aqueous phase is a critical pathway to produce the light-absorbing N-containing secondary organic compounds(SOC).The formation mechanism of these compounds has been wildly investigated in bulk solutions with a low ionic strength.However,the ionic strength in the aqueous phase of the polluted atmosphere may be higher.It is still unclear whether and to what extent the inorganic ions can affect the SOC formation.Here we prepared the bulk solution with certain ionic strength,in which glyoxal and ammonium were mixed to mimic the aqueous-phase reaction.Molecular characterization by High-resolution Mass Spectrometry was performed to identify the N-containing products,and the light absorption of the mixtures was measured by ultraviolet-visible spectroscopy.Thirty-nine N-containing compounds were identified and divided into four categories(N-heterocyclic chromophores,high-molecular-weight compounds with N-heterocycle,aliphatic imines/hemiaminals,and the unclassified).It was observed that the longer reaction time and higher ionic strength led to the formation of more N-heterocyclic chromophores and the increasing of the lightabsorbance of the mixture.The added inorganic ions were proposed to make the aqueous phase somewhat viscous so that the molecules were prone to undergo consecutive and intramolecular reactions to form the heterocycles.In general,this study revealed that the enhanced ionic strength and prolonged reaction time had the promotion effect on the lightabsorbing SOC formation.It implies that the aldehyde-derived aqueous-phase SOC would contribute more light-absorbing particulate matter in the industrial or populated area where inorganic ions are abundant.展开更多
文摘An asymmetric aza-Diels-Alder and O-Michael addition sequence has been developed to construct chiral hy- dropyrano[2,3-b]pyridine derivatives with good yields and excellent stereoselectivity, by starting with N-Ts-l-aza- 1,3-butadienes and aliphatic aldehydes tethered to an α,β-unsaturated ketone motif. A tandem O-Michael addition reaction was completed via acid catalysis.
基金supported by the National Natural Science Foundation of China(Nos.31930002,21621002,21877002,81991525,82273829 and 22077007)the key project at central government level:the ability establishment of sustainable use for valuable Chinese medicine resources(2060302-2201-17).
文摘Dihydrofolate reductase(DHFR),a housekeeping enzyme in primary metabolism,has been extensively studied as a model of acid-base catalysis and a clinic drug target.Herein,we investigated the enzymology of a DHFR-like protein SacH in safracin(SAC)biosynthesis,which reductively inactivates hemiaminal pharmacophore-containing biosynthetic intermediates and antibiotics for self-resistance.Furthermore,based on the crystal structure of SacH−NADPH−SAC-A ternary complexes and mutagenesis,we proposed a catalytic mechanism that is distinct from the previously characterized short-chain dehydrogenases/reductases-mediated inactivation of hemiaminal pharmacophore.These findings expand the functions of DHFR family proteins,reveal that the common reaction can be catalyzed by distinct family of enzymes,and imply the possibility for the discovery of novel antibiotics with hemiaminal pharmacophore.
基金supported by the National Natural Science Foundation of China(Nos.21976034,42077193,92044301,and21906024)the Shanghai Municipal Health Commission Science and Research Fund(No.202040185)+1 种基金the Shanghai Pudong New District Bureau of Ecology and Environment Research Project(No.PDHJ20210008)the Guangdong Provincial Observation and Research Station for Coastal Atmosphere and Climate of the Great Bay Area(No.2021B1212050024)。
文摘The reaction of carbonyl-to-imine/hemiaminal conversion in the atmospheric aqueous phase is a critical pathway to produce the light-absorbing N-containing secondary organic compounds(SOC).The formation mechanism of these compounds has been wildly investigated in bulk solutions with a low ionic strength.However,the ionic strength in the aqueous phase of the polluted atmosphere may be higher.It is still unclear whether and to what extent the inorganic ions can affect the SOC formation.Here we prepared the bulk solution with certain ionic strength,in which glyoxal and ammonium were mixed to mimic the aqueous-phase reaction.Molecular characterization by High-resolution Mass Spectrometry was performed to identify the N-containing products,and the light absorption of the mixtures was measured by ultraviolet-visible spectroscopy.Thirty-nine N-containing compounds were identified and divided into four categories(N-heterocyclic chromophores,high-molecular-weight compounds with N-heterocycle,aliphatic imines/hemiaminals,and the unclassified).It was observed that the longer reaction time and higher ionic strength led to the formation of more N-heterocyclic chromophores and the increasing of the lightabsorbance of the mixture.The added inorganic ions were proposed to make the aqueous phase somewhat viscous so that the molecules were prone to undergo consecutive and intramolecular reactions to form the heterocycles.In general,this study revealed that the enhanced ionic strength and prolonged reaction time had the promotion effect on the lightabsorbing SOC formation.It implies that the aldehyde-derived aqueous-phase SOC would contribute more light-absorbing particulate matter in the industrial or populated area where inorganic ions are abundant.
