Four Stereoisomers of 2-Aminomethyl-1-cyclopropanecarboxylic Acid: Synthesis and Biological Evaluation

Abstract

Here, we report a practical method for asymmetric synthesis of cyclopropane-fused GABA analogs. Starting from 2-furaldehyde, the cis-isomer (CAMP) was synthesized over 10 steps; (−)- and (+)-CAMP·HCl were synthesized by employing d- and l-menthol as the chiral auxiliary for total 2.5% and 1.3% yields, respectively. On the other hand, the trans-isomer (TAMP) was elaborated via double asymmetric induction, i.e. organocatalytic asymmetric cyclopropanation on chiral substrate. Thus, starting from l- and d-menthyl acrylate, in combination with quinidine-derived and quinine-derived organocatalysts, (−)- and (+)-TAMP·HCl were synthesized in total 6.6% and 3.7% yields, respectively, over 8 steps each. Configurational analysis of the synthetic intermediates based on 13C NMR is also reported. Preliminary oncological assays showed the weak but specific activities of CAMP and TAMP as the molecular basis of GABA analogs, which are still left unexplored.

Isolation and Structure Elucidation of JBIR-157, a Skeletally Novel Aromatic Polyketide Produced by the Heterologous Expression of a Cryptic Gene Cluster

“…18) Calculation of 13 C-NMR Chemical Shift Values of 2 Calculated 13 C-NMR data were obtained employing ωB97X-V/6-311 + G(2DF,2P)-[6-311G*]//ωB97X-D/6-31G* model based on the literature. [19][20][21] The calculated 13 C-NMR chemical shift values were expected by DFT calculation. The calculations were performed with Spartan '20.…”

Metal or Metal-Free Catalysis for the Oxidation of Biosourced Furfural

“…The respective observed yields are 85% (2 steps) and 81% (4 steps) under environmentally friendly conditions. 47 Under similar conditions, Oikawa et al report the photooxidation of furfural used as a starting material for the synthesis of GABA analogs functionalized with a cyclopropane 48 and Chen et al for the preparation of γ-butyrolactone by selective deoxygenation of 5-HFO obtained by the same method. 49 All these results illustrate the significant potential of furfural and 5-hydroxyfuranone as biosourced raw materials through various applications in fine chemistry and materials science.…”

JBIR-155, a Specific Class D β-Lactamase Inhibitor of Microbial Origin

“…The relative configuration of the 4-hydroxy-2-methyl-6-oxabicyclo[3.2.0]­heptan-7-one skeleton is strongly supported by comparison to the theoretical 13 C chemical shift values predicted by density functional theory (DFT) calculations (Figure S1, Table S2). , The relative stereochemistry of the C-23 methyl group on the fatty side chain was determined by the JBCA method based on 3 J C,H values obtained using J -resolved HMBC spectral analysis of 2 . , At the C-3/C-7 axis, a large coupling constant between H-3 and C-23 ( 3 J H‑3, C‑23 = 5.8 Hz) and H-7 and C-4 ( 3 J H‑7, C‑4 = 6.0 Hz) implied the anti orientation of H-3/C-23 and H-7/C-4, respectively (Figure e). By taking into consideration these results, the absolute configuration of JBIR-155 ( 1 ) was elucidated as shown in Figure .…”