Chemo-enzymatic synthesis of chiral 3-substituted tetrahydroquinolines by a sequential biocatalytic cascade and Buchwald–Hartwig cyclization

Abstract

Chiral 3-substituted tetrahydroquinolines are important structure units in natural products and biologically active compounds. However, the efficient asymmetric synthesis of these interesting scaffolds is still a challenging task. Herein a...

Cobalt-and-Nitrogen-Doped Carbon Nanoparticle Catalysts for Selective Hydrogen Transfer Reactions

“…To further extend the validation of Co–N/C applicability, the catalyst was also employed in the hydrogenation of 2-methylquinoline 6a under comparatively milder reaction conditions. This holds significant relevance within the realms of fine chemicals, pharmaceuticals, agrochemicals, petrochemicals, and hydrogen storage. − After establishing the optimal conditions (Table S7), we proceeded to explore the substrate scope. For the model substrate, an impressive yield of 96% was achieved ( 7a , Table ).…”

Chemo-enzymatic synthesis of bioactive compounds from traditional Chinese medicine and medicinal plants

“…[9] Examples of bioactive compounds produced by chemo-enzymatic synthesis are shown in Table 1. [2,[8][9][10][11][12][13][14][15][16][17][18] Thalidomide is first marketed in Germany in the 1950s as a sedative and analgesic, primarily for the relief of nausea and vomiting during pregnancy. It is typically racemic, consisting of a pair of enantiomers: (R)-thalidomide exhibits potent sedative effects, while (S)-thalidomide is associated with immunomodulation.…”

“…It is noteworthy that the gram-scale production of (S)-4a and (S)-6a, which are key intermediates of the antithrombotic drug (21S)argatroban, has been achieved. [18]…”

“…LG-23/17β-HSDcl [9] Podophyllotoxin Anti-cancer activity DPS [2,8,10] Digoxin Treating heart failure CYP14A [11] Spiroindimicins Potent antiparasitic activity LaStaO/LzrO-VioB [12] Thalidomide Immunoregulation IdgS-Ox* R539A [13] Gedunin HSP90 inhibition MERO1 L437A [14] C-glycosides Potential SGLT2 inhibitors AbCGT [15] Cotylenol Cytotoxicity on human myeloid leukemia cells BscD/Bsc9 [16] Eponemycin Antitumor cytotoxic agent EpnF [17] C3STQ A unit of anti-Parkinson agent sumanirole ERED-IRED [18] in a specific chiral form. This discovery sheds light on the biosynthesis of (R)-benzylisoquinoline alkaloids for the first time.…”

Engineered Imine Reductase for Asymmetric Synthesis of Dextromethorphan Key Intermediate

“…Imine reductases (IREDs) have been applied to catalyze reduction of various imines such as pyrrolines, piperidines, azepines, sulfur-containing cyclic imines, 3 H -indoles, tetrahydro-β-carbolines, and dihydroisoquinolines. − IREDs and reductive aminases also catalyze asymmetric reductive amination of carbonyl compounds to form the corresponding chiral α- or β-amines. − One-pot biocatalytic cascade of ene reductases and IREDs and a multifunctional biocatalyst EneIRED have been applied for the synthesis of chiral amines from α,β-unsaturated ketones, aldehydes, or imines; however, IREDs can only catalyze the reduction of imines or reductive amination of ketones and aldehydes instead of α,β-unsaturated compounds in most cases. − In 2019, we identified a group of highly hindrance-tolerant IREDs that could efficiently convert 1-benzyl-HHIQs derivatives into the corresponding 1-benzyl-OHIQs including ( S )- 2a in 98% ee values . However, the low specific activity (0.035 U/mg) and low substrate concentration (10 mM) limit its practical application.…”