4876-00-0

Upstream product

• 4876-02-2 N-(3,4-dimethoxyphenethyl)-phenyl acetamide 
• 14301-36-1 N-[2-(3,4-dimethoxyphenyl)ethyl]formamide 
• 93-97-0 benzoic acid anhydride 
• 120-20-7 2-(3,4-dimethoxyphenyl)-ethylamine 
• 103-80-0 phenylacetyl chloride 
• 101-97-3 Ethyl 2-phenylethanoate 
• 6125-24-2 2-Phenylnitroethane 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 39220-86-5 2-nitro-1-(3,4-dimethoxyphenyl)ethanol 
• 103-82-2 phenylacetic acid 
• 77199-00-9 N-(2-<3,4-dimethoxyphenyl>-ethyl)-benzene-sulfonylamide 
• 894419-48-8 N-[2-(4,5-dimethoxy-2-phenylacetylphenyl)ethyl]formamide 

Downstream Products

• 23818-73-7 6,7-dimethoxy-1-benzylisoquinoline 
• 3423-37-8 1-benzyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 22190-45-0 (6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)(phenyl)methanone 
• 3972-79-0 1-benzyl-2-formyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 64229-28-3 C₄₆H₅₈N₂O₈⁽²⁺⁾*2I^(1-) 
• 81165-36-8 3-(1-Benzyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propionic acid 2-[3-(1-benzyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propionyloxy]-ethyl ester; compound with oxalic acid 
• 1126908-64-2 1-(α,α-dichlorobenzyl)-3,4-dihydro-6,7-dimethoxyisoquinoline 
• 47145-37-9 (1R)-1,2,3,4-tetrahydro-1-benzoyl-6,7-dimethoxyisoquinoline 
• 3423-13-0 1-benzyl-6,7-dimethoxy-N-methyl-1,2,3,4-tetrahydroisoquinoline 
• 4875-97-2 1-benzyl-6,7-dimethoxy-2-methyl-3,4-dihydro-isoquinolinium iodide 

Relevant academic research and scientific papers

Design, synthesis, and biological evaluation of tetrahydroisoquinolines derivatives as novel, selective PDE4 inhibitors for antipsoriasis treatment

Psoriasis is a kind of chronic inflammatory skin disorder, while the long-term use of conventional therapies for this disease are limited by severe adverse effects. Novel small molecules associated with new therapeutic mechanisms are greatly needed. It is known that phosphodiesterase 4 (PDE4) plays a central role in regulating inflammatory responses through hydrolyzing intracellular cyclic adenosine monophosphate (cAMP), making PDE4 to be an important target for the treatment of inflammatory diseases (e.g. psoriasis). In our previous work, we identified a series of novel PDE4 inhibitors with a tetrahydroisoquinoline scaffold through structure-based drug design, among which compound 1 showed moderate inhibition activity against PDE4. In this study, a series of novel tetrahydroisoquinoline derivatives were developed based on the crystal structure of PDE4D in complex with compound 1. Anti-inflammatory effects of these compounds were evaluated, and compound 36, with high safety, permeability and selectivity, exhibited significant inhibitory potency against the enzymatic activity of PDE4D and the TNF-α release from the LPS-stimulated RAW 264.7 and hPBMCs. Moreover, an in vivo study demonstrated that a topical administration of 36 achieved more significant efficacy than calcipotriol to improve the features of psoriasis-like skin inflammation. Overall, our study provides a basis for further development of tetrahydroisoquinoline-based PDE4 inhibitors against psoriasis.

Enhancement of the carbamate activation rate enabled syntheses of tetracyclic benzolactams: 8-oxoberbines and their 5- And 7-membered C-ring homologues

A route to the direct amidation of aromatic-ring-tetheredN-carbamoyl tetrahydroisoquinoline substrates was developed. This route enabled general access to 8-oxoberberines and their 5- and 7- membered C-ring homologues. It overcomes the undesired tandem side-reactions that result in the destruction of the isoquinoline backbone, which inevitably occurred under our previously reported superacidic carbamate activation method.

Copper(ii)-catalyzed and acid-promoted highly regioselective oxidation of tautomerizable C(sp3)-H bonds adjacent to 3,4-dihydroisoquinolines using air (O2) as a clean oxidant

A mild, efficient and eco-friendly method for the oxidation of 1-Bn-DHIQs to 1-Bz-DHIQs without concomitant excessive oxidation of 1-Bz-DHIQs to 1-Bz-IQs is very important for the syntheses of 1-Bz-DHIQ alkaloids and analogues. In this article, we developed a novel Cu(ii)-catalyzed and acid-promoted highly regioselective oxidation of tautomerizable C(sp3)-H bonds adjacent to the C-1 positions of various 1-Bn-DHIQs. It was observed that when 0.2 equiv. of Cu(OAc)2·2H2O was used as the catalyst, 3.0 equiv. of AcOH was used as the additive and air (O2) was used as a clean oxidant, various 1-Bn-DHIQs could be efficiently oxidized to corresponding 1-Bz-DHIQs at 25 °C in DMSO. Especially, almost no concomitant excessive oxidation of 1-Bz-DHIQs to 1-Bz-IQs was observed during the above reaction. In addition, this method was successfully applied in the first total synthesis of the alkaloid canelillinoxine.

Synthesis of N-Heterocycles by Reductive Cyclization of Nitroalkenes Using Molybdenum Hexacarbonyl as Carbon Monoxide Surrogate

The development of a method that uses molybdenum hexacarbonyl [Mo(CO)6] as carbon monoxide (CO) surrogate for the palladium-catalyzed reductive cyclization of nitroalkenes into indoles or thienopyrroles is reported. Several types of nitroalkenes could be transformed into the desired products in excellent yields and in most cases with complete regioselectivities and higher yields than those previously reported with palladium/CO system.

Development of Pd(OAc)2-catalyzed tandem oxidation of C[sbnd]N, C[sbnd]C, and C(sp3)–H bonds: Concise synthesis of 1-aroylisoquinoline, oxoaporphine, and 8-oxyprotoberberine alkaloids

A catalytic tandem oxidation of C[sbnd]N, C[sbnd]C, and C(sp3)–H bonds is developed. This tandem oxidation is applied to two-step total syntheses of papaveraldine and pulcheotine A. Additionally, the total synthesis of liriodenine is achieved in six steps from homopiperonyl alcohol and 2-bromophenylacetonitrile by applying this catalytic tandem oxidation. Moreover, the direct conversion of xylopinine to 8-oxypseudopalmatine in a 76% yield demonstrates the versatility of this catalytic reaction.

Synthesis of 3,4-dihydroisoquinolines using nitroalkanes in polyphosphoric acid

A new method for the synthesis of 6,7-dimethoxy-3,4-dihydroisoquinoline based on the reaction of 2-(3,4-dimethoxyphenyl)ethan-1-amine (homoveratrylamine) with aliphatic nitro compounds in polyphosphoric acid (PPA) was developed.

Reactions of 3,4-dihydroisoquinolines and dihydrothieno[3,2-c]pyridines with benzyne

Cyanomethyl-substituted tetrahydroisoquinolines and tetrahydrothieno[3,2-c]pyridines were synthesized by multicomponent reaction of the dihydro analogues of aforesaid systems with benzyne and acetonitrile. The products obtained relate to alkaloids of isoq

Designing new analogs for streamlining the structure of cytotoxic lamellarin natural products

Despite the therapeutic potential of marine-derived lamellarin natural products, their preclinical development has been hampered by their lipophilic nature, causing very poor aqueous solubility. In order to develop more drug-like analogs, their structure was streamlined in this study from both the cytotoxic activity and lipophilicity standpoints. First, a modified total synthetic route was successfully devised to construct a library of 59 systematically designed lamellarin analogs, which were then subjected to cytotoxicity and log P determinations. Along with the 25 first-generation lamellarins previously synthesized in our laboratory, the structure-activity and structure-lipophilicity relationships were extensively evaluated. Our results clearly indicated the additional structural requirements around the lamellarin skeleton which, when combined with those reported previously, can provide invaluable guidance for further modifications to increase the aqueous solubility of these compounds.

Synthesis of 8-oxoberbines and related benzolactams by Pd(OAc) 2-catalyzed direct aromatic carbonylation

A variety of alkoxy-substituted benzolactams with a berbine or yohimbane skeleton were prepared from 1-benzyl-1,2,3,4-tetrahydroisoquinolines or 1-benzyl-1,2,3,4-tetrahydro-β-carbolines by a phosphine-free Pd(II)-catalyzed direct aromatic carbonylation in a Pd(OAc)2-Cu(OAc) 2 catalytic system. The site selectivity was compared with that of the carbonylation with Pd(OAc)2 or Pd(OAc)2·2 PPh3, respectively.

Synthesis of pyrido[2,1-a]isoquinolin-4-ones and oxazino[2,3-a]isoquinolin- 4-ones: New inhibitors of mitochondrial respiratory chain

Benzo[a]quinolizine is an important heterocyclic framework that can be found in numerous bioactive compounds. The general scheme for the synthesis of these compounds was based on the preparation of the appropriate dihydroisoquinolines by Bischler-Napieral