(4R,5S)-4-甲基-3,5-二羟基己酸特丁酯的化学-生物合成

以2-甲基-3-羰基丁酸乙酯为原料,以面包酵母为生物催化剂,采用化学-生物法合成了光学纯（4R,5S）-5-羟基-3-羰基-4-甲基己酸（99.2％ee）。

生物-化学法合成黑色素前体5,6-二羟基吲哚

研究了偶联Saccharomyces cerevisiae BY4741/pYX212-TYR催化L-多巴(L-Dopa)合成多巴色素(DC)的生物氧化步骤和DC还原合成5,6-二羟基吲哚(DHI)化学步骤,实现了DHI的生物-化学合成.通过优化生物氧化步骤的反应条件及供氧策略等因素,使L-Dopa的转化率提升至94.75%;通过优化化学还原步骤反应条件及化学助剂,使DHI的产率提高到90.03%.产物的超高效液相色谱-四极杆飞行时间质谱联用(UPLC-Q-TOF-MS)分析结果表明,反应体系中存在DHI可溶性低聚物.

Formation kinetics and transition mechanism of CaO·SiO2 in low-calcium system during high-temperature sintering

The crystal structure,formation kinetics and micro-morphology of CaO·SiO2 during high-temperature sintering process were studied in low-calcium system by XRD,FT-IR,Raman and SEM-EDS methods.When the molar ratio of CaCO3 to SiO2 is 1.0,β-2CaO·SiO2 forms firstly during the heating process,and then CaO·SiO2 is generated by the transformation reaction of pre-formed 2CaO·SiO2 with SiO2.3CaO·SiO2 and 3CaO·2SiO2 do not form either in the heating or sintering process.Rising the sintering temperature and prolonging the holding time promote the phase transition of 2CaO·SiO2 to CaO·SiO2,resulting in the sintered products a small blue shift and broadening in Raman spectra.The content of CS can reach 97.4%when sintered at 1400℃ for 1 h.The formation kinetics of CaO·SiO2 follows the second-order chemical reaction model,and the corresponding apparent activation energy and pre-exponential factor are 505.82 kJ/mol and 2.16×10^14 s^−1 respectively.

Total Synthesis of Anisodine

Aim To design a practical synthetic route of anisodine. Methods Starting from3α-hydroxy-6β-acetyltropine, anisodine was synthesized in 11 steps. Result Anisodine wasobtainded with an overall yield of 2.6 % . Conclusion Total synthetic route of anisodine wasachieved which may afford a possible route for commercial preparation of anisodine.

Advancements in biocatalysis:From computational to metabolic engineering

Through several waves of technological research and un‐matched innovation strategies,bio‐catalysis has been widely used at the industrial level.Because of the value of enzymes,methods for producing value‐added compounds and industrially‐relevant fine chemicals through biological methods have been developed.A broad spectrum of numerous biochemical pathways is catalyzed by enzymes,including enzymes that have not been identified.However,low catalytic efficacy,low stability,inhibition by non‐cognate substrates,and intolerance to the harsh reaction conditions required for some chemical processes are considered as major limitations in applied bio‐catalysis.Thus,the development of green catalysts with multi‐catalytic features along with higher efficacy and induced stability are important for bio‐catalysis.Implementation of computational science with metabolic engineering,synthetic biology,and machine learning routes offers novel alternatives for engineering novel catalysts.Here,we describe the role of synthetic biology and metabolic engineering in catalysis.Machine learning algorithms for catalysis and the choice of an algorithm for predicting protein‐ligand interactions are discussed.The importance of molecular docking in predicting binding and catalytic functions is reviewed.Finally,we describe future challenges and perspectives.

The Combinatorial Biosynthesis of＂Unnatural＂ Products with Polyketides

Polyketides have been widely used clinically due to their significant biological activities, but the needed structural and functional diversity cannot be achieved by common chemical synthetic methods. The tool of combinatorial biosynthesis provides the possibility to produce "unnatural" natural drugs, which has achieved initial success. This paper provides an overview for the strategies of combinatorial biosynthesis in producing the structural and functional diversity of polyketides, including the redesign of metabolic flow, polyketide synthase(PKS) engineering, and PKS post-translational modification. Although encouraging progress has been made in the last decade, challenges still exist regarding the rational combinatorial biosynthesis of polyketides. In this review, the perspectives of polyketide combinatorial biosynthesis are also discussed.

Exotic Beam for Direct Measurement of the 22^Mg＋a

The scattering and resonance reactions of ^22Mg＋p and ^22Mg＋α play crucial roles for studying deeply not only in the structure of proton-rich nuclei of ^23A1 and ^26Si but also for the interest of astrophysics. It is believed that ^22Mg nucleus is a waiting point in the αp-process of nucleosynthesis in novae. We supposed to perform direct measurement the ^22Mg＋α system in invert kinematics using radioactive ion （RI） beam. The ^22Mg beam of 3.73 MeV/u was produced at CRIB facility of the University of Tokyo located at RIKEN, Japan in 2011. In this paper, we report the results the scattering and resonance reactions with the alpha target. of the ^22Mg beam production used for the direct measurement of

Biosynthesis-based artificial evolution of microbial natural products

Natural products are often secondary metabolites in living organisms with a wide variety of biological activities. The diversification of their structures, aiming to the search for biologically active small molecules by expanding chemical and functional spaces, is a major area of current interest in synthetic chemistry. However, developing synthetic accessibility and efficiency often faces challenges associated with structural complexity. Synthetic biology has recently emerged and is promising to accomplish complex molecules; by contrast, the application to structural diversification of natural products relies on the understanding, development and utilization of compatible biosynthetic machinery. Here, we review the strategies primarily concerning the artificial evolution of microbial natural products whose biosynthesis features template enzymology, including ribosomaUy synthesized and post-translationally modified peptides as well as the assembly line-resultant polyketides, non-ribosomal peptides and hybrids. The establishment of these approaches largely facilitates the expansion of the molecular diversity and utility through bioengineering at different stages/levels of biosynthetic pathways.

Diversity-oriented synthesis of bicyclic ring systems via a conjugate addition/aldol/RCM process

Diversity-oriented synthesis （DOS） has been widely applied in the generation of a large collection of highly functionalized molecules with diverse chemical skeletons. Herein, we report the diversity-oriented synthesis of a series of structurally diverse bicyclic substrates via an efficient tandem conjugate addition/aldol process followed by ring-closing metathesis （RCM）. This approach allows us to efficiently prepare a number of structurally complex molecules for the further chemical biology studies.

Biological evaluation of 2-methylpyrimidine derivatives as active pan Bcr-Abl inhibitors

We designed a series of 2-methylpyrimidine derivatives as new BCR-ABL inhibitors using scaffold-hopping strategy.These synthetic compounds exhibited significant inhibition against a broad spectrum of Bcr-Abl mutants including the gatekeeper T315I mutant.Compound 7u showed very potent kinase inhibitory activities against Bcr-Abl WT,Bcr-Abl E255K,Bcr-Abl Q252H,Bcr-Abl G250E and Bcr-Abl T315I,with IC50 values of 0.13 nM,0.17 nM,0.24 nM,0.19 nM and 0.65μM,respectively.This compound also displayed anti-proliferation activity against K562 cell line with an IC50 value of 1.1 nM,thus representing a new lead for further optimization.

Chemomics and drug innovation

Chemomics is an interdisciplinary study using approaches from chemoinformatics,bioinformatics,synthetic chemistry,and other related disciplines.Biological systems make natural products from endogenous small molecules (natural product building blocks) through a sequence of enzyme catalytic reactions.For each reaction,the natural product building blocks may contribute a group of atoms to the target natural product.We describe this group of atoms as a chemoyl.A chemome is the complete set of chemoyls in an organism.Chemomics studies chemomes and the principles of natural product syntheses and evolutions.Driven by survival and reproductive demands,biological systems have developed effective protocols to synthesize natural products in order to respond to environmental changes;this results in biological and chemical diversity.In recent years,it has been realized that one of the bottlenecks in drug discovery is the lack of chemical resources for drug screening.Chemomics may solve this problem by revealing the rules governing the creation of chemical diversity in biological systems,and by developing biomimetic synthesis approaches to make quasi natural product libraries for drug screening.This treatise introduces chemomics and outlines its contents and potential applications in the fields of drug innovation.

The synthesis of benzoxaboroles and their applications in medicinal chemistry

Benzoxaborole,as a versatile scaffold,plays important roles in organic synthesis,molecular recognition and supramolecular chemistry.It is also a privileged structure in medicinal chemistry due to its desirable physicochemical and drug-like properties.Recently,benzoxaboroles were widely applied as antifungal,antibacterial,antiviral,anti-parasite,and anti-inflammatory agents.This review covers the properties,synthetic methods and applications of benzoxaboroles in medicinal chemistry.

Rational design and functional evolution of targeted peptides for bioanalytical applications

The complicated, highly dynamic and diverse nature of biosystems brings great challenges to the specific analysis of molecular processes of interest. Nature provides antibodies for the specific recognition of antigens, which is a straight-forward way for targeted analysis. However, there are still limitations during the practical applications due to the big size of the antibodies, which accelerate the discovery of small molecular probes. Peptides built from various optional building blocks and easily achieved by chemical synthetic approaches with predictable conformations, are versatile and can act as tailor-made targeting vehicles.In this mini review, we summarize the recent developments in the discovery of novel peptides for bioanalytical and biomedical applications. Progresses in peptide-library design and selection strategies are presented. Recent achievements in the peptide-guided detection, imaging and disease treatment are also focused.