610296-40-7

Upstream product

• 64-04-0 phenethylamine 
• 346689-66-5 2-methyl-N-phenethylbenzamide 
• 610298-61-8 1-(2'-methylphenyl)-3,4-dihydroisoquinoline 
• 933-88-0 ortho-toluoyl chloride 
• 610296-41-8 1-(2-methylphenyl)-1,2,3,4-tetrahydroisoquinoline 

Downstream Products

• 610296-32-7 N-(indan-2-yl)-N-(2-fluorobenzyl)-2-[(1S)-1-(2-methylphenyl)-3,4-dihydroisoquinolin-2(1H)-yl]acetamide 

Relevant academic research and scientific papers

Asymmetric Transfer Hydrogenation of Unhindered and Non-Electron-Rich 1-Aryl Dihydroisoquinolines with High Enantioselectivity

The use of arene/Ru/TsDPEN catalysts bearing a heterocyclic group on the TsDPEN in the asymmetric transfer hydrogenation (ATH) of dihydroisoquinolines (DHIQs) containing meta- or para-substituted aromatic groups at the 1-position results in the formation of products of high enantiomeric excess. Previously, only 1-(ortho-substituted)aryl DHIQs, or with an electron-rich fused ring gave products with high enantioselectivity; therefore, this approach solves a long-standing challenge for imine ATH.

Enantioselective synthesis of 1-Aryl-substituted tetrahydroisoquinolines employing imine reductase

Tetrahydroisoquinolines (THIQs) with a C1-aryl-substituted groups are common in many natural and synthetic compounds of biological importance. Currently, their enantioselective synthesis are primarily reliant on chemical catalysis. Enzymatic synthesis using imine reductase is very attractive, because of the cost-effectiveness, high catalytic efficiency, and enantioselectivity. However, the steric hindrance of the 1-aryl substituents make this conversion very challenging, and current successful examples are mostly restricted to the simple alkyl-THIQs. In this report, through extensive evaluation of a large collection of IREDs (including 88 enzymes), we successfully identified a panel of steric-hindrance tolerated IREDs. These enzymes are able to convert meta- and para-substituted chloro-, methyl-, and methoxyl-benzyl dihydroisoquinolines (DHIQs) into corresponding R- or S- THIQs with very high enantioselectivity and conversion. Among them, the two most hindrance-tolerated enzymes (with different stereospecificity) are also able to convert ortho-substituted chloro-, methyl-, and methoxyl-benzyl DHIQs and dimethoxyl 1-chlorobenzyl-DHIQs with good enantiometric excess. Furthermore, using in silico modeling, a highly conserved tryptophan residue (W191) was identified to be critical for substrate accommodation in the binding cavity of the S-selective IRED (IR45). Replacing W191 with alanine can dramatically increase the catalytic performance by decreasing the Km value by 2 orders of magnitude. Our results provide an effective route to synthesize these important classes of THIQs. Moreover, the disclosed sequences and substrate binding model set a solid basis to generate more-efficient and broad-selective enzymes via protein engineering.

Enantioselective Synthesis of 1-Aryl-Substituted Tetrahydroisoquinolines Through Ru-Catalyzed Asymmetric Transfer Hydrogenation

A convenient and general asymmetric transfer hydrogenation of a wide array of 1-aryl-3,4-dihydroisoquinoline derivatives using a [RuIICl(η6-benzene)TsDPEN] complex in combination with a 5:2 HCOOH-Et3N azeotropic mixture as a hydrogen source was developed. Under mild reaction conditions, the described catalytic transformation secured a practical synthetic access to the corresponding valuable chiral 1-aryltetrahydroisoquinoline units with high atom economy, a broad substrate scope, high isolated yields (up to 97%) and good to excellent enantioselectivities (up to 99% ee). It was found that the stereochemical outcome of the reaction was strongly influenced by both the structure of the catalyst and the substituents present on the substrate. The synthetic utility of the present protocol has been demonstrated through the asymmetric synthesis of several biologically important alkaloids including the antiepileptic drug agent 1c, as well as (-)-nor-cryptostyline alkaloids I and II.

Substituted tetrahydroisoquinolines as C5a receptor modulators

Substituted tetrahydroisoquinolines and related compounds are provided. Such compounds are ligands that may be used to modulate C5a receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions associated with pathologi