490-53-9Relevant academic research and scientific papers
Structure and Biocatalytic Scope of Coclaurine N-Methyltransferase
Bennett, Matthew R.,Thompson, Mark L.,Shepherd, Sarah A.,Dunstan, Mark S.,Herbert, Abigail J.,Smith, Duncan R. M.,Cronin, Victoria A.,Menon, Binuraj R. K.,Levy, Colin,Micklefield, Jason
, p. 10600 - 10604 (2018/08/17)
Benzylisoquinoline alkaloids (BIAs) are a structurally diverse family of plant secondary metabolites, which have been exploited to develop analgesics, antibiotics, antitumor agents, and other therapeutic agents. Biosynthesis of BIAs proceeds via a common pathway from tyrosine to (S)-reticulene at which point the pathway diverges. Coclaurine N-methyltransferase (CNMT) is a key enzyme in the pathway to (S)-reticulene, installing the N-methyl substituent that is essential for the bioactivity of many BIAs. In this paper, we describe the first crystal structure of CNMT which, along with mutagenesis studies, defines the enzymes active site architecture. The specificity of CNMT was also explored with a range of natural and synthetic substrates as well as co-factor analogues. Knowledge from this study could be used to generate improved CNMT variants required to produce BIAs or synthetic derivatives.
Oxidation of Trialkylamines by BrCCl3: Scope, Applications and Mechanistic Aspects
Nauth, Alexander M.,Orejarena Pacheco, Julio Cesar,Pusch, Stefan,Opatz, Till
, p. 6966 - 6974 (2017/12/26)
The catalyst-free photochemical reaction of trialkylamines and BrCCl3 induced by visible light was investigated. The outcome of the reaction was found to depend strongly on the nature of the amine substrates. N-Methyl-1,2,3,4-tetrahydroisoquino
Synthesis of 1-substituted tetrahydroisoquinolines by lithiation and electrophilic quenching guided by in situ IR and NMR spectroscopy and application to the synthesis of salsolidine, carnegine and laudanosine
Li, Xiabing,Leonori, Daniele,Sheikh, Nadeem S.,Coldham, Iain
, p. 7724 - 7730 (2013/07/19)
The lithiation of N-tert-butoxycarbonyl (N-Boc)-1,2,3,4- tetrahydroisoquinoline was optimized by in situ IR (ReactIR) spectroscopy. Optimum conditions were found by using n-butyllithium in THF at -50 °C for less than 5 min. The intermediate organolithium was quenched with electrophiles to give 1-substituted 1,2,3,4-tetrahydroisoquinolines. Monitoring the lithiation by IR or NMR spectroscopy showed that one rotamer reacts quickly and the barrier to rotation of the Boc group was determined by variable-temperature NMR spectroscopy and found to be about 60.8 kJ mol-1, equating to a half-life for rotation of approximately 30 s at -50 °C. The use of (-)-sparteine as a ligand led to low levels of enantioselectivity after electrophilic quenching and the "poor man's Hoffmann test" indicated that the organolithium was configurationally unstable. The chemistry was applied to N-Boc-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline and led to the efficient synthesis of the racemic alkaloids salsolidine, carnegine, norlaudanosine and laudanosine. Copyright
Synthesis of new dopamine D1 antagonist SCH 23390 analogues by the stereoselective stevens rearrangement
Ariza, Manuela,Diaz, Amelia,Suau, Rafael,Valpuesta, Maria
experimental part, p. 6507 - 6518 (2011/12/05)
A convenient synthesis for new SCH 23390 analogues bearing different substituents at the C-1 position has been developed by using the diastereoselective Stevens rearrangement. This procedure has provided a good number of new 1,2-disubstituted 1H-3-benzaze
Transfer hydrogenation of isoquinolinium salts catalyzed by a rhodium complex
Wu, Jiashou,Liao, Jian,Zhu, Jin,Deng, Jingen
, p. 2059 - 2062 (2008/02/05)
Regio- and chemoselective transfer hydrogenation of isoquinolinium salts catalyzed by [Cp*RhCl2]2 using HCOOH-Et3N (5:2) as a hydrogen source was realized. A variety of N-methyl- and N-benzyl-1,2,3,4-tetrahydroisoquinoline
Synthesis and biological evaluation of N-methyl-laudanosine iodide analogues as potential SK channel blockers
Graulich,Mercier,Scuvee-Moreau,Seutin,Liegeois
, p. 1201 - 1209 (2007/10/03)
Neuronal action potentials are followed by an afterhyperpolarisation (AHP), which is mediated by small conductance Ca2+-activated K+ channels (SK channels or KCa2 channels). This AHP plays an important role in regulating neuronal act
Indium metal as a reducing agent in organic synthesis
Pitts,Harrison,Moody
, p. 955 - 977 (2007/10/03)
The low first ionisation potential (5.8 eV) of indium coupled with its stability towards air and water, suggest that this metallic element should be a useful reducing agent for organic substrates. The use of indium metal for the reduction of C=N bonds in imines, the heterocyclic ring in benzo-fused nitrogen heterocycles, of oximes, nitro compounds and conjugated alkenes and the removal of 4-nitrobenzyl protecting groups is described. Thus the heterocyclic ring in quinolines, isoquinolines and quinoxalines is selectively reduced using indium metal in aqueous ethanolic ammonium chloride. Treatment of a range of aromatic nitro compounds under similar conditions results in selective reduction of the nitro groups; ester, nitrile, amide and halide substituents are unaffected. Likewise indium in aqueous ethanolic ammonium chloride is an effective method for the deprotection of 4-nitrobenzyl ethers and esters. Indium is also an effective reducing agent under non-aqueous conditions and α-oximino carbonyl compounds can be selectively reduced to the corresponding N-protected amine with indium powder, acetic acid in THF in the presence of acetic anhydride or di-tert-butyl dicarbonate. Conjugated alkenes are also reduced by indium in THF-acetic acid.
A highly efficient synthesis of 1-methyl-, 1-benzyl-, and 1-phenyl-1,2,3,4-tetrahydroisoquinolines by a modified pummerer reaction
Shinohara, Tatsumi,Takeda, Akira,Toda, Jun,Terasawa, Noriyo,Sano, Takehiro
, p. 555 - 565 (2007/10/03)
(±)-1-Methyl- (13b), (±)-1-benzyl- (13c), and (±)-1-phenyl- (13d)-1,2,3,4-tetrahydroisoquinolines, which are supposed to participate in the pathogenesis of Parkinson's disease, were prepared by using a modified Pummerer reaction as a key step in excellent overall yields from the commercially available ketones (4b-c).
Synthesis of isoquinolines from 2-phenylethylamines, amides, nitriles and carboxylic acids in polyphosphoric acid
Venkov, Atanas P.,Ivanov, Ilian I.
, p. 12299 - 12308 (2007/10/03)
A convenient one pot synthesis of 1-, 1.3-substituted 3,4-dihydroisoquinolines 5 enamines 10 and 3-oxo-2,3-dihydroisoquinolines 18 as well as of enamides 22 of isoquinoline from 2-phenyl-, 1,2-diphenylethylamines, phenylacetamides, phenylacetonitriles, N-acylphenylethylamines and carboxylic acids in nonaqueous media has been accomplished.
Application of the intermolecular α-amido-alkylation reaction for the synthesis of tertiary amides and 1-substituted 2-acyltetrahydroisoquinolines. Synthesis of (±)-carnegine
Venkov,Statkova-Abeghe
, p. 1817 - 1824 (2007/10/02)
Adducts 4 of Schiff bases and 3,4-dihydroisoquinolines with acyl chlorides react with Grignard reagents 5 in an intermolecular α-amidoalkylation reaction to the corresponding tertiary amides or 1-substituted 2-acyltetrahydroisoquinolines.
