3423-14-1

Usage

InChI:InChI=1/C19H23NO3/c1-20-9-8-14-11-18(22-2)19(23-3)12-16(14)17(20)10-13-4-6-15(21)7-5-13/h4-7,11-12,17,21H,8-10H2,1-3H3

Upstream product

• 228271-22-5 6,7-dimethoxy-1-[[4-[5-(6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinolinyl)methyl-2-methoxy]phenoxy]benzyl]-2-methyl-1,2,3,4-tetrahydroisoquinoline 
• 14199-15-6 Methyl 4-hydroxyphenylacetate 
• 1580442-46-1 C₅₃H₅₈N₂O₈ 
• 1246431-52-6 C₁₉H₁₇Cl₃O₇ 
• 518-94-5 (-)-cycleanine 
• 6392-40-1 N-Norarmepavine 
• 50-00-0 formaldehyd 
• 5990-67-0 d-tetrandrine 
• 5884-31-1 2-(4-benzyloxyphenyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]acetamide 
• 42971-27-7 2-(benzo[d][1,3]dioxol-5-yl)-N-(3,4-dimethoxyphenethyl)acetamide 
• 3472-22-8 N-norarmepavine 
• 1260158-09-5 1-(4-isopropoxybenzyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline 
• 1246431-54-8 C₁₈H₁₅Cl₃O₆ 
• 1580442-44-9 methyl 2-{4-hydroxy-3-[4-(2-methoxy-2-oxoethyl)phenoxy]phenyl}acetate 

Downstream Products

• 5701-00-8 (R)-O-methylarmepavine 
• 36417-79-5 2-methylisococlaurine 

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.

Gene editing and synthetically accessible inhibitors reveal role for TPC2 in HCC cell proliferation and tumor growth

The role of two-pore channel 2 (TPC2), one of the few cation channels localized on endolysosomal membranes, in cancer remains poorly understood. Here, we report that TPC2 knockout reduces proliferation of cancer cells in vitro, affects their energy metabolism, and successfully abrogates tumor growth in vivo. Concurrently, we have developed simplified analogs of the alkaloid tetrandrine as potent TPC2 inhibitors by screening a library of synthesized benzyltetrahydroisoquinoline derivatives. Removal of dispensable substructures of the lead molecule tetrandrine increases antiproliferative properties against cancer cells and impairs proangiogenic signaling of endothelial cells to a greater extent than tetrandrine. Simultaneously, toxic effects on non-cancerous cells are reduced, allowing in vivo administration and revealing a TPC2 inhibitor with antitumor efficacy in mice. Hence, our study unveils TPC2 as valid target for cancer therapy and provides easily accessible tetrandrine analogs as a promising option for effective pharmacological interference.

Organocatalytic Enantioselective Pictet-Spengler Approach to Biologically Relevant 1-Benzyl-1,2,3,4-Tetrahydroisoquinoline Alkaloids

(Figure Presented) A general procedure for the synthesis of 1-benzyl-1,2,3,4-tetrahydroisoquinolines was developed, based on organocatalytic, regio- and enantioselective Pictet-Spengler reactions (86-92% ee) of N-(o-nitrophenylsulfenyl)-2-arylethylamines with arylacetaldehydes. The presence of the o-nitrophenylsulfenyl group, together with the MOM-protection in the catechol part of the tetrahydroisoquinoline ring system, appeared to be a productive combination. To demonstrate the versatility of this approach, 10 biologically and pharmaceutically relevant alkaloids were prepared using (R)-TRIP as the chiral catalyst: (R)-norcoclaurine, (R)-coclaurine, (R)-norreticuline, (R)-reticuline, (R)-trimemetoquinol, (R)-armepavine, (R)-norprotosinomenine, (R)-protosinomenine, (R)-laudanosine, and (R)-5-methoxylaudanosine.

Synthesis of (+)-O-methylthalibrine by employing a stereocontrolled Bischler-Napieralski reaction and an electrochemically generated diaryl ether

An efficient electrochemical four-step route was developed for the preparation of diaryl ether derivatives by using halogenation and dehalogenation processes in addition to electrochemical phenolic oxidation and reduction reactions. The synthesis of (+)-O

Synthesis of alkaloids by stevens rearrangement of nitrile-stabilized ammonium ylides: (±)-laudanosine, (±)-laudanidine, (±)-armepavine, (±)-7-methoxycryptopleurine, and (±)-xylopinine

The Stevens rearrangement of nitrile-stabilized ammonium ylides in conjunction with the reductive removal of the nitrile function permits the facile construction of α-branched amines from α-aminonitriles. We employed this reaction sequence for the preparation of (±)-laudanosine, (±)-laudanidine and (±)-armepavine, (±)-7- methoxycryptopleurine, and (±)-xylopinine from two closely related and readily accessible bicyclic α-aminonitriles. The final products were obtained in high to almost quantitative yields (71-98%) from the quaternary ammonium salts obtained by N-alkylation of these starting materials.

Enantioselective synthesis of tetrahydroprotoberberines and bisbenzylisoquinoline alkaloids from a deprotonated α-aminonitrile

Under controlled conditions, 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline- 1-carbonitrile can be quantitatively deprotonated in the α-position. Its alkylation directly furnishes 3,4-dihydroisoquinolines which can serve as starting materials for the preparation of various alkaloids. Here, the preparation of the benzylisoquinolines (+)-laudanidine, (+)-armepavine, and (+)-laudanosine as well as the tetrahydroprotoberberines ( - )-corytenchine and ( - )-tetrahydropseudoepiberberine using Noyori's asymmetric transfer hydrogenation are described. The dimeric alkaloids (+)-O-methylthalibrine and (+)-tetramethylmagnolamine were obtained from nonracemic precursors in Ullmann diaryl ether syntheses.

Total synthesis of (±)-armepavines and (±)-nuciferines from (2-nitroethenyl)benzene derivatives

A concise route to armepavine 1 and nuciferine 2 and 3, which can be isolated from the leaves of Nelumbo nucifera (Nymphaceae), has been achieved in which the longest linear sequence is only six steps from commercially available benzaldehyde in 28%, 21%, and 20% overall yield, respectively. The key transformations in the synthesis are the radical cyclization of aryl bromide with Bu3SnH and the Pictet-Spengler reaction of N-substituted amine with aldehyde. Copyright Taylor & Francis Group, LLC.

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

Effect of isoquinoline alkaloids of different structural types on antiplatelet aggregation in vitro

Forty-one isoquinoline alkaloids were tested for antiplatelet aggregation effects. Among them, (-)-discretamine (6), protopine (7), ochotensimine (18), O-methylarmepavinemethine (23), lindoldhamine (25), isotetrandrine (26), thalicarpine (27), papaverine (28), and D-(+)-N-norarmepavine (32) exhibited significant inhibitory activity towards adenosine 5′-diphosphate (ADP)-, arachidonic acid (AA)-, collagen-, and/or platelet-activating factor (PAF)-induced platelet aggregation. The results are discussed on the basis of structure-activity relationships. Georg Thieme Verlag KG Stuttgart.

Isolation and preparation of 3H-tetrandrine

Tetrandrine is a biabenzytehahydroisoquinoline alkaloid. Its structure is vary complex and the preparation of labeled derivatives is difficult. We have prepared 3H-tatrandrine using the tritium gas exposure method. This method produces many fragments which make isolation and purification of small quantities difficult. We investigated these fragments of unlabeled d-tetrandrine and found almost all contain one to several hydroxide groups. Using this information, we designed a two-step paper chromatography method for isolation and purification of 3H-Tetrandrine. This method involves the application of a pH 4.7 Na2HPO4-citric acid buffer to the paper to block the migration of hydroxide group fragments of tetrandrine. 3H-tetrandrine was successfully with a radiochemical purity of 90%.