Dihydrofolate reductase-like protein inactivates hemiaminal pharmacophore for self-resistance in safracin biosynthesis

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.

吲哚基半缩醛胺多孔材料的制备及其对甲基橙的吸附性能

为了去除废水中的甲基橙染料,以胱胺和色胺为原料,通过与甲醛反应成功制备了吲哚基半缩醛胺多孔材料,利用傅里叶红外光谱仪和扫描电子显微镜对其结构和形貌进行了表征,研究了吲哚基半缩醛胺多孔材料对甲基橙的吸附性能和吸附机理。结果表明:当吸附时间为20 min时,吲哚基半缩醛胺多孔材料对甲基橙的吸附量达到29.114 mg/g,吸附性能良好,其吸附过程符合准二级动力学模型。

Aqueous-phase formation of N-containing secondary organic compounds affected by the ionic strength

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.

Anion cascade reactions Ⅲ:Synthesis of 3-isoquinuclidone bridged polycyclic lactams

Bridged polycyclic lactams are important structural units in organic functional materials,natural products,and pharmaceuticals.A flexible and efficient anion cascade reaction was developed for the preparation of bridged polycyclic lactams from readily available malonamides and 1,4‑dien-3-ones.Various highly substituted bridged polycyclic lactams were synthesized in good to excellent yields by tandem nucleophilic sequences in the presence of t BuOK in commercially available EtOH solvent at 60℃.Notably,the simple reactions can be run on a gram scale.Mechanistically,bis-Michael addition reaction and hemiaminalization reactions are involved in the tandem transformation.

不对称有机催化构筑二环己内酰胺类化合物

设计了一例α,β-不饱和烯醛与含有双亲核活性中心的α-酮酰胺不对称有机催化高选择性的Michael-hemiaminalization-hemiacetalization串联反应,并以高收率(up to 97%)、优异的对映选择性和非对映选择性(up to>99%ee,>20∶1 dr)获得一系列具有两个顺式手性中心的二环己内酰胺化合物.

Asymmetric Sequential Aza-Diels-Alder and O-Michael Addition： Efficient Construction of Chiral Hydropyrano[2,3-b]pyridines

一个不对称的 aza-Diels-Alder 和 O-Michael 增加序列被开发了构造 chiral hydropyrano [2,3-b ] 有好收益和优秀 stereoselectivity 的 pyridine 衍生物，由以拴住到的 N-Ts-1-aza-1,3-butadienes 和脂肪族的醛开始一，不饱和的酉同类主题。双人脚踏车 O-Michael 增加反应经由酸催化作用被完成。