6392-40-1

Upstream product

• 913985-87-2 8',9'-dimethoxy-1',5',6',10b'-tetrahydro-4H-spiro(cyclohexa-2,5-diene-1,2'-pyrrolo[2,1-a]isoquinoline)-3',4-dione 
• 836-42-0 4-benzyloxybenzyl chloride 
• 156-38-7 4-hydroxyphenylacetate 
• 120-20-7 2-(3,4-dimethoxyphenyl)-ethylamine 
• 10214-84-3 N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-hydroxyphenyl)acetamide 
• 123285-94-9 (3R,10bS)-8,9-dimethoxy-3-phenyl-2,3,5,6-tetrahydro-10bH-oxazolo<2.3-a>isoquinoline 
• 47626-99-3 1-(4-(benzyloxy)benzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline 
• 56441-69-1 2-<4-(phenylmethoxy)phenyl>acetic acid ethyl ester 
• 655245-11-7 1-(4-benzyloxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 
• 1609169-60-9 tert-butyl 1-(4-hydroxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1609169-59-6 tert-butyl 1-(4-(benzyloxy)benzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 5884-31-1 2-(4-benzyloxyphenyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]acetamide 
• 611182-78-6 [4-(bromomethyl)phenoxy][tri(propan-2-yl)]silane 
• 1210-57-7 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-1-carbonitrile 

Downstream Products

• 5701-00-8 (R)-O-methylarmepavine 

Relevant academic research and scientific papers

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet-Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

We present a systematic investigation on an improved variant of the N-acyl-Pictet-Spengler condensation for the synthesis of 1-benzyltetrahydroisoquinolines, based on our recently published synthesis of N-methylcoclaurine, exemplified by the total syntheses of 10 alkaloids in racemic form. Major advantages are a) using ω-methoxystyrenes as convenient alternatives to arylacetaldehydes, and b) using the ethoxycarbonyl residue for both activating the arylethylamine precursors for the cyclization reaction, and, as a significant extension, also as protective group for phenolic residues. After ring closure, the ethoxycarbonyl-protected phenols are deprotected simultaneously with the further processing of the carbamate group, either following route A (lithium alanate reduction) to give N-methylated phenolic products, or following route B (treatment with excess methyllithium) to give the corresponding alkaloids with free N-H function. This dual use of the ethoxycarbonyl group shortens the synthetic routes to hydroxylated 1-benzyltetrahydroisoquinolines significantly. Not surprisingly, these ten alkaloids did not show noteworthy effects on TPC2 cation channels and the tumor cell line VCR-R CEM, and did not exhibit P-glycoprotein blocking activity. But due to their free phenolic groups they can serve as valuable intermediates for novel derivatives addressing all of these targets, based on previous evidence for structure-activity relationships in this chemotype.

Multienzyme One-Pot Cascades Incorporating Methyltransferases for the Strategic Diversification of Tetrahydroisoquinoline Alkaloids

The tetrahydroisoquinoline (THIQ) ring system is present in a large variety of structurally diverse natural products exhibiting a wide range of biological activities. Routes to mimic the biosynthetic pathways to such alkaloids, by building cascade reactions in vitro, represents a successful strategy and can offer better stereoselectivities than traditional synthetic methods. S-Adenosylmethionine (SAM)-dependent methyltransferases are crucial in the biosynthesis and diversification of THIQs; however, their application is often limited in vitro by the high cost of SAM and low substrate scope. In this study, we describe the use of methyltransferases in vitro in multi-enzyme cascades, including for the generation of SAM in situ. Up to seven enzymes were used for the regioselective diversification of natural and non-natural THIQs on an enzymatic preparative scale. Regioselectivites of the methyltransferases were dependent on the group at C-1 and presence of fluorine in the THIQs. An interesting dual activity was also discovered for the catechol methyltransferases used, which were found to be able to regioselectively methylate two different catechols in a single molecule.

Total Synthesis of (S, S)-Tetramethylmagnolamine via Aerobic Desymmetrization

We describe a concise synthesis of the pseudodimeric tetrahydroisoqunoline alkaloid (S,S)-tetramethylmagnolamine by a catalytic aerobic desymmetrization of phenols. Desymmetrization reactions increase molecular complexity with high levels of efficiency, b

Effect of 1-Substitution on Tetrahydroisoquinolines as Selective Antagonists for the Orexin-1 Receptor

Selective blockade of the orexin-1 receptor (OX1) has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain's reward system. We have recently reported a series of tetrahydroisoquinoline-based OX1 selective antagonists. Aimed at elucidating structure-activity relationship requirements in other regions of the molecule and further enhancing OX1 potency and selectivity, we have designed and synthesized a series of analogues bearing a variety of substituents at the 1-position of the tetrahydroisoquinoline. The results show that an optimally substituted benzyl group is required for activity at the OX1 receptor. Several compounds with improved potency and/or selectivity have been identified. When combined with structural modifications that were previously found to improve selectivity, we have identified compound 73 (RTIOX-251) with an apparent dissociation constant (Ke) of 16.1 nM at the OX1 receptor and >620-fold selectivity over the OX2 receptor. In vivo, compound 73 was shown to block the development of locomotor sensitization to cocaine in rats. (Chemical Equation Presented).

Design, synthesis and biological evaluation of benzylisoquinoline derivatives as multifunctional agents against Alzheimer's disease

A novel series of benzylisoquinoline derivatives were designed, synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). The screening results showed that most of the compounds significantly inhibited cholinesterases (ChEs),

1,3-benzyl migration in iminium ions: Evidence for a fast free-radical chain reaction

The "exocyclic" 1,3-benzyl shift observed in iminium salts derived from 1-benzyl-1,2,3,4-tetrahydroisoquinolines is related to the "endocyclic" Knabe rearrangement. A crossover experiment, isotopic labelling, the study of initiators and inhibitors as well as DFT calculations of gas-phase model structures provide evidence for a free-radical pathway under kinetic entropy control that is not affected by "slow" radical traps. An unexpected rearrangement of methyleneiminium ions derived from 1-benzyl-1,2,3,4-tetrahydroisoquinolines has been investigated by isotopic labelling, trapping experiments and DFT calculations. Theobserved benzyl migration proceeds by an exceptionally fast radical chain reaction closely related to the Knabe reaction.Remarkably, the process is inhibited byneither methyl acrylate nor dioxygen. Copyright

Unexpected unique behavior of spiro-isoquinolines with a cyclohexadienone system in attempted dienone-phenol rearrangement

8',9'-Dimethoxy-1',5',6',10b'-tetrahydro-4H-spiro(cyclohexa-2,5-diene-1,2'-pyrrolo[2,1-a]isoquinoline)-3',4-dione 2 with a basic skeleton of a natural product, annnosqualine, exhibited unique behavior in a dienone-phenol rearrangement. Treatment of 2 with trifluoroacetic acid gave a simple 1-benzylisoquinoline alkaloid, norarmepavine 4. Plausible reaction mechanism for the observed transformation is also described.

Method and health food for preventing and/or alleviating psychiatric disorder, and/or for effectuating sedation

A method for preventing and/or alleviating a psychiatric disorder, and/or effectuating sedation, comprising administering a benzylisoquinoline derivative represented by General Formula (I): wherein R1, R2, R3 and X each re

Enantioselective synthesis of the tetrahydrobenzyl-isoquinoline alkaloid (-)-norarmepavine using polymer supported reagents

We describe, in full, the enantioselective synthesis of the tetrahydrobenzylisoquinoline alkaloid (-)-norarmepavine (1) in 77% e.e. This compound was prepared using solid-supported reagents and scavengers in multi-step sequences of reactions to give mater

Simplified tetrandrine congeners as possible antihypertensive agents with a dual mechanism of action

A series of O- and/or N-substituted derivatives of (±)-coclaurine (1a) were synthesized as simplified structural mimics of the antihypertensive alkaloid tetrandrine (2) and assayed for binding to brain cortical sites labeled with the α1-adrener