5843-65-2

Usage

Uses

Used in Pharmaceutical Industry:
Demethyl-Coclaurine is used as a neuroprotective agent for the prevention and treatment of Alzheimer's disease. It inhibits the release of high-mobility group box 1 (HMGB1) protein, which is associated with neuroinflammation and neuronal damage in Alzheimer's disease.
Used in Respiratory Therapy:
Demethyl-Coclaurine is used as a bronchodilator to improve lung function in various respiratory diseases. It helps to relax and widen the airways, making it easier to breathe.
Used in Antiviral Applications:
Demethyl-Coclaurine can be used to prevent and treat viral infections by binding to the SARS-CoV-2 spike protein and human angiotensin-converting enzyme 2 (ACE2) complex, thereby inhibiting viral entry into host cells.
Used in Ketogenic Diets:
Demethyl-Coclaurine is used as a racemic salt-acidic compound to produce elevated and sustained ketosis. It helps to increase the production of ketone bodies, which can be used as an alternative energy source by the brain and other tissues during periods of low carbohydrate availability.
Used in Antioxidant Therapy:
Demethyl-Coclaurine is used as an antioxidant in lipid-like environments. It helps to neutralize free radicals and protect cells from oxidative damage, which can contribute to various diseases and aging.
Used in Neuroprotection:
Demethyl-Coclaurine acts through inhibition of middle cerebral artery occlusion (MCAO)-mediated HMGB1 release in vivo, making it useful towards ischemic injuries and neuroprotection.

InChI:InChI=1/C16H17NO3/c18-12-3-1-10(2-4-12)7-14-13-9-16(20)15(19)8-11(13)5-6-17-14/h1-4,8-9,14,17-20H,5-7H2

Upstream product

• 51-61-6 dopamine 
• 7339-87-9 4-hydroxyphenylacetaldehyde 
• 59-92-7 levodopa 
• 51-67-2 tyrosamine 
• 60-18-4 L-tyrosine 
• 1421820-28-1 (1S)-6,7-dimethoxy-1-[(4-methoxyphenyl)methyl]-2-((1S)-1-phenylethyl)-1,2,3,4-tetrahydroisoquinoline 
• 1421820-27-0 N-[2-(3,4-dimethoxyphenyl)ethyl]-N-[1-((1S)-phenyl)ethyl]-2-(4-methoxyphenyl)acetamide 
• 114105-51-0 (S)-(-)-[2-(3,4-dimethoxyphenyl)ethyl](1-phenylethyl)amine 
• 114105-64-5 (S)-(+)-2-(3,4-dimethoxyphenyl)-N-(1-phenylethyl)acetamide 
• 93-40-3 (3,4-Dimethoxyphenyl)acetic acid 
• 41498-37-7 7,12-O,O'-dimethylcoclaurine 
• 5703-26-4 4-Methoxyphenylacetaldehyde 
• 104-01-8 4-Methoxyphenylacetic acid 
• 2746-25-0 p-Methoxybenzyl bromide 

Downstream Products

• 66277-20-1 1,2,3,4-tetrahydro-1-[(4-hydroxyphenyl)methyl]-2-methyl-6,7-Isoquinolinediol 
• 1421820-29-2 C₂₁H₂₅NO₅ 
• 1421820-31-6 (2S)-1-(6,7-dihydroxy-1-(4-hydroxybenzyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3,3,3-trifluoro-2-methoxy-2-phenylpropan-1-one 
• 106032-53-5 (1R)-1-(4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol 
• 5843-65-2 (1S)-1-(4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol 
• 1421820-30-5 (2S)-1-((1S)-6,7-dihydroxy-1-(4-hydroxybenzyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3,3,3-trifluoro-2-methoxy-2-phenylpropan-1-one 
• 486-39-5 Coclaurine 
• 3472-22-8 N-norarmepavine 

Relevant academic research and scientific papers

A multi-omics strategy resolves the elusive nature of alkaloids in Podophyllum species

Podophyllum hexandrum and, to a much lesser extent P. peltatum, are sources of podophyllotoxin, extensively used as a chemical scaffold for various anti-cancer drugs. In this study, integrated omics technologies (including advanced mass spectrometry/metabolomics, transcriptome sequencing/gene assemblies, and bioinformatics) gave unequivocal evidence that both plant species possess a hitherto unknown aporphine alkaloid metabolic pathway. Specifically, RNA-seq transcriptome sequencing and bioinformatics guided gene assemblies/analyses in silico suggested presence of transcripts homologous to genes encoding all known steps in aporphine alkaloid biosynthesis. A comprehensive metabolomics analysis, including UPLC-TOF-MS and MALDI-MS imaging in situ, then enabled detection, identification, localization and quantification of the aporphine alkaloids, magnoflorine, corytuberine and muricinine, in the underground and aerial tissues. Interestingly, the purported presence of alkaloids in Podophyllum species has been enigmatic since the 19th century, remaining unresolved until now. The evolutionary and phylogenetic ramifications of this discovery are discussed. This journal is

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.

Design and Use of de novo Cascades for the Biosynthesis of New Benzylisoquinoline Alkaloids

The benzylisoquinoline alkaloids (BIAs) are an important group of secondary metabolites from higher plants and have been reported to show significant biological activities. The production of BIAs through synthetic biology approaches provides a higher-yielding strategy than traditional synthetic methods or isolation from plant material. However, the reconstruction of BIA pathways in microorganisms by combining heterologous enzymes can also give access to BIAs through cascade reactions. Most importantly, non-natural BIAs can be generated through such artificial pathways. In the current study, we describe the use of tyrosinases and decarboxylases and combine these with a transaminase enzyme and norcoclaurine synthase for the efficient synthesis of several BIAs, including six non-natural alkaloids, in cascades from l-tyrosine and analogues.

Synthesis technology of higenamine and pharmaceutical salt of higenamine

The invention discloses a synthesis technology of higenamine and pharmaceutical salt of the higenamine, and belongs to the technical field of medicine synthesis. According to the synthesis technology,4-methoxyphenylacetic acid is used as a raw material, and through steps of reduction, oxidation, cyclization, deprotection and the like, the higenamine and the hydrochloride of the higenamine are obtained. Compared with existing technical routes, the synthesis technology has the few steps, and is simple to operate, the raw material is cheap, reaction conditions are mild, a reaction process is easy to control, the total yield and the purity are high, and the synthesis technology is environmentally friendly, safe and suitable for industrial production, and has large industrial prospects.

Compositions and methods for producing benzylisoquinoline alkaloids

The present invention relates to host cells that produce compounds that are characterized as benzylisoquinolines, as well as select precursors and intermediates thereof. The host cells comprise one, two or more heterologous coding sequences wherein each of the heterologous coding sequences encodes an enzyme involved in the metabolic pathway of a benzylisoquinoline, or its precursors or intermediates from a starting compound. The invention also relates to methods of producing the benzylisoquinoline, as well as select precursors and intermediates thereof by culturing the host cells under culture conditions that promote expression of the enzymes that produce the benzylisoquinoline or precursors or intermediates thereof.

Facile one-pot synthesis of tetrahydroisoquinolines from amino acids via hypochlorite-mediated decarboxylation and Pictet-Spengler condensation

A convenient method for oxidative decarboxylation of α-amino acids is presented. The aldehyde products may be isolated or converted to tetrahydroisoquinolines by addition of dopamine via Pictet-Spengler reaction. Racemic products are generated by phosphate buffer >300 mM to maximize regioselectivity. (S)-Enantiomer products are generated by norcoclaurine synthase reaction in maleic acid buffer to minimize chemical background reaction.

The catalytic potential of Coptis japonica NCS2 revealed - Development and utilisation of a fluorescamine-based assay ETI

The versatility and potential of a norcoclaurine synthase (NCS) from Coptis japonica NCS2 has been investigated, together with the development and application of a novel fluorescence-based high-throughput assay using nearly forty amines/aldehydes. The stereocontrol exerted by CjNCS2 on selected non-natural substrates has been determined, where the tetrahydroisoquinolines (THIAs) were formed as the (1S)-isomer in >95% ee, as observed with the natural product norcoclaurine. Docking calculations involving THIA mechanism intermediates, utilising the reported Thalictrum flavum NCS X-ray crystallographic structure, were carried out and combined with the CjNCS2 screening results to further understand the mode of action of NCS. These findings suggested that in addition to the key active-site residues K122 and E110, D141 is also mechanistically essential for the enzymatic transformation. The exceptional tolerance of NCS towards aldehyde substrates is furthermore supported by our proposed mechanism in which the aldehydes protrude out of the enzymatic pocket. Copyright

Biocatalytic production of tetrahydroisoquinolines

The promiscuity of the enzyme norcoclaurine synthase is described. This biocatalyst yielded a diverse array of substituted tetrahydroisoquinolines by cyclizing dopamine with various acetaldehydes in a Pictet-Spengler reaction. This enzymatic reaction may provide a biocatalytic route to a range of tetrahydroisoquinoline alkaloids.

Phosphate mediated biomimetic synthesis of tetrahydroisoquinoline alkaloids

A one-pot synthesis of tetrahydroisoquinoline alkaloids in a phosphate buffer has been achieved, and a reaction mechanism proposed. The utilisation of mild reaction conditions readily afforded a range of isoquinolines, including norcoclaurine.