13949-67-2Relevant articles and documents
Stereoinversion in the diastereoselective acylation of benzoxazine derivatives with 2-aryloxypropionyl chlorides
Vakarov,Korolyova,Gruzdev,Pervova,Levit,Krasnov
, p. 1257 - 1263 (2019)
A comparative study of the kinetic resolution of racemic derivatives of 3,4-dihydro-3-methyl-2H-[1,4]benzoxazine using racemic 2-aryloxypropionyl chlorides was performed. It was found that the acylation of racemic amines with racemic 2-(1-naphthyloxy)propionyl chloride leads to amides enriched with (3R*,2′R*)-diastereomers, while the acylation with 2-phenoxypropionyl chloride gives predominantly (3R*,2′S*)-amides. Quantum chemical modeling of the process of kinetic resolution at the COSMO-CH2Cl2-B3LYP-D3-gCP/def2-TZVP//B3LYP-D3-gCP/def2-SVP level of theory was performed. The computational results are in a good agreement with the experimental data.
Access to Optically Enriched α-Aryloxycarboxylic Esters via Carbene-Catalyzed Dynamic Kinetic Resolution and Transesterification
Liu, Bin,Song, Runjiang,Xu, Jun,Majhi, Pankaj Kumar,Yang, Xing,Yang, Song,Jin, Zhichao,Chi, Yonggui Robin
supporting information, p. 3335 - 3338 (2020/04/30)
Optically active α-aryloxycarboxylic acids and their derivatives are important functional molecules. Disclosed here is a carbene-catalyzed dynamic kinetic resolution and transesterification reaction for access to this class of molecules with up to 99% yields and 99:1 er values. Addition of a chiral carbene catalyst to the ester substrate leads to two diastereomeric azolium ester intermediates that can quickly epimerize to each other and thus allows for effective dynamic kinetic resolution to be realized. The optically enriched ester products from our reaction can be quickly transformed to chiral herbicides and other bioactive molecules.
Optimization of benzoxazole-based inhibitors of Cryptosporidium parvum inosine 5′-monophosphate dehydrogenase
Gorla, Suresh Kumar,Kavitha, Mandapati,Zhang, Minjia,Chin, James En Wai,Liu, Xiaoping,Striepen, Boris,Makowska-Grzyska, Magdalena,Kim, Youngchang,Joachimiak, Andrzej,Hedstrom, Lizbeth,Cuny, Gregory D.
, p. 4028 - 4043 (2013/06/27)
Cryptosporidium parvum is an enteric protozoan parasite that has emerged as a major cause of diarrhea, malnutrition, and gastroenteritis and poses a potential bioterrorism threat. C. parvum synthesizes guanine nucleotides from host adenosine in a streamlined pathway that relies on inosine 5′-monophosphate dehydrogenase (IMPDH). We have previously identified several parasite-selective C. parvum IMPDH (CpIMPDH) inhibitors by high-throughput screening. In this paper, we report the structure-activity relationship (SAR) for a series of benzoxazole derivatives with many compounds demonstrating CpIMPDH IC50 values in the nanomolar range and >500-fold selectivity over human IMPDH (hIMPDH). Unlike previously reported CpIMPDH inhibitors, these compounds are competitive inhibitors versus NAD +. The SAR study reveals that pyridine and other small heteroaromatic substituents are required at the 2-position of the benzoxazole for potent inhibitory activity. In addition, several other SAR conclusions are highlighted with regard to the benzoxazole and the amide portion of the inhibitor, including preferred stereochemistry. An X-ray crystal structure of a representative E·IMP·inhibitor complex is also presented. Overall, the secondary amine derivative 15a demonstrated excellent CpIMPDH inhibitory activity (IC 50 = 0.5 ± 0.1 nM) and moderate stability (t1/2 = 44 min) in mouse liver microsomes. Compound 73, the racemic version of 15a, also displayed superb antiparasitic activity in a Toxoplasma gondii strain that relies on CpIMPDH (EC50 = 20 ± 20 nM), and selectivity versus a wild-type T. gondii strain (200-fold). No toxicity was observed (LD 50 > 50 μM) against a panel of four mammalian cells lines.