1036765-71-5Relevant articles and documents
Total Synthesis and Structural Reassignment of Aspergillomarasmine A
Liao, Daohong,Yang, Shaoqiang,Wang, Jianyu,Zhang, Jian,Hong, Benke,Wu, Fan,Lei, Xiaoguang
, p. 4291 - 4295 (2016)
The increase and spread of Gram-negative bacteria that resistant are to almost all currently available β-lactam antibiotics is a major global health problem. The primary cause for drug resistance is the acquisition of metallo-β-lactamases such as metallo-β-lactamase-1 (NDM-1). The fungal natural product aspergillomarasmine A (AMA), a fungal natural product, is an inhibitor of NDM-1 and has shown promising in vivo therapeutic potential in a mouse model infected with NDM-1-expressing Gram-negative bacteria. The first total synthesis and stereochemical configuration reassignment of aspergillomarasmine A is reported. The synthesis highlights a flexible route and an effective strategy to achieve the required oxidation state at a late stage. This modular route is amenable to the efficient preparation of analogues for the development of metallo-β-lactamase inhibitors to potentiate β-lactam antibiotics.
Chiral Titanium Coordination Assemblies: Robust Cooperative Self-Supported Catalysts for Asymmetric Ring Opening of meso-Epoxides with Aliphatic Amines
Sun, Zheming,Chen, Jiangbo,Liu, Yaoqi,Tu, Tao
, p. 494 - 505 (2017/02/10)
By utilizing the oxygen bridge in dimeric μ-oxo-titanium-salen complexes as an efficient cross-linkage, a series of robust chiral titanium coordination assemblies has been successfully fabricated with the ditopic bridging ligands derived from BINOL and salen derivatives via coordination polymerization, which are fully characterized by IR, elemental analysis, XRD and microscopic studies. Because of their insolubility in most organic solvents and water, these metal-organic assemblies can successfully function as robust self-supported chiral catalysts, allowing an asymmetric ring opening (ARO) of meso-epoxides with aliphatic amines. Remarkably, owing to the linkage effects and the cooperation of two kinds of chiral titanium moieties in the metal-organic assemblies, the self-supported chiral catalysts demonstrate extremely high stability. They not only show high tolerance towards various meso-epoxides and nucleophilic aliphatic amines, but also can be reused in more than 20 runs without obvious metal leaching and loss in yields and enantioselectivities. Furthermore, the self-supported catalyst accomplished a one-pot tandem olefin epoxidation and ARO of an epoxide sequence starting from the olefin, 30% hydrogen peroxide and benzylamine. In marked contrast, the reaction failed to work when using the two corresponding homogeneous catalysts under identical reaction conditions. Good yields and enantioselectivities were obtained by the robust self-supported catalyst, which clearly indicates the cooperative effects between two chiral moieties within the metal-organic assemblies. The two catalytic centers can perform their own duties without interference and this further supports our strategy for the self-supported catalyst design. (Figure presented.).
Insight into the mechanism of the asymmetric ring-opening aminolysis of 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane catalyzed by titanium/BINOLate/ water system: Evidence for the Ti(BINOLate)2-bearing active catalyst entities and the role of water
Bao, Hongli,Zhou, Jing,Wang, Zheng,Guo, Yinlong,You, Tianpa,Ding, Kuiling
supporting information; experimental part, p. 10116 - 10127 (2009/02/03)
The mechanism of the enantioselective ring-opening aminolysis of 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane with benzylamine, catalyzed by the titanium-BINOLate species generated in situ from a mixture of enantiopure BINOL (1,1′-bi-2-naphthol), Ti(OiPr)4, and H2O in the presence of benzylamine in toluene, was investigated in detail using a combination of reaction profile measurements, nonlinear effect (NLE) studies, solution 1H NMR analysis, electrospray ionization mass spectrometry (ESI-MS), as well as the results obtained from screening of dynamic catalyst library of complexes La/Ti/Lb (La or L b = chiral diol ligands). The BINOL-to-titanium ratio and the presence or absence of water in the catalytic system were found to exert profound influences on both reactivity and enantioselectivity of the reaction. The NLE studies revealed that the titanium species involved in the catalysis should contain more than one BINOL unit, either within or at the periphery of the catalytic cycle. ESI-MS analysis of the catalytic systems provided strong support in favor of the mechanistic proposal that titanium complexes bearing the Ti(BINOLate)2 moiety should be the active species responsible for the catalysis, which was further confirmed by the observation of synergistic effect of the heteroligand combinations during screening of the dynamic catalyst library. ESI-MS analysis of the reaction system indicated that water does not take part in the catalyst generation, which is an unprecedented finding in contrast to the previous mechanistic understandings in the titanium catalytic chemistry involving the participation of water. Most probably, water functions as a proton shuttle in the catalysis, facilitating the proton transfer between the reactants. Furthermore, the origin of (+)-NLE observed in the present catalytic system is rationalized on the basis of the ESI-MS analysis of the catalyst system prepared from a 1:1 pseudoracemic mixture of (S)-BINOL and (R)-3,3′,6,6′-D4-BINOL. Finally, the reactivity differences between several couples of epoxide/amine combinations were tentatively rationalized on the basis of the arguments on their relative coordination preferences, and several other aliphatic amines were also found to efficiently ring-open the titled epoxide in excellent enantioselectivities. The results from this study are expected to shed some light on the often elusive chemistry of Ti(IV)-based catalytic systems where water or molecular sieves (or alcohols, etc.) are found to play an important yet inexplicable role and may help the search for effective asymmetric Ti(IV) catalysts for other types of reactions.
