91-21-4 Usage
Description
1,2,3,4-Tetrahydroisoquinoline is a tetrahydroisoquinoline compound that is found in various drugs, including the muscle relaxant tubocurarine. It is a clear yellow to brown liquid and has a wide range of applications in the pharmaceutical industry.
Uses
Used in Pharmaceutical Industry:
1,2,3,4-Tetrahydroisoquinoline is used as a reagent in the preparation of 4-(1,2,4-oxadiazol-5-yl)piperidine-1-carboxamides, which are antiproliferative tubulin inhibitors. These inhibitors have potential applications in cancer treatment by preventing the proliferation of cancer cells.
1,2,3,4-Tetrahydroisoquinoline can also be used for the synthesis of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), which has strong applications in peptides and peptidomimetics design and discovery. This makes it a valuable compound for the development of new drugs and therapeutic agents.
Additionally, 1,2,3,4-tetrahydroisoquinoline has been made into some derivatives with potential for prevention of parkinsonism, cancer treatment, and acting as Anticonvulsant Agents. These applications highlight its versatility and importance in the pharmaceutical industry.
Synthesis
To a solution of the isoquinolinone (1.156 g, 9.90 mmol) and tert-butyl alcohol
(0.88 mL, 11.9 mmol) in THF (30 mL) at ?78 °C was added liquid ammonia (about
280 mL). Lithium was added in small pieces until the blue coloration persisted, after
which the solution was stirred at ?78 °C for 30 min. The blue coloration was dissipated
with piperlyne, 4-methoxybenzyl chloride (4.83 g, 31.00 mmol) in THF (5 mL)
was introduced by syringe, and the mixture was stirred for an additional 150 min at
?78 °C. Solid ammonium chloride was added and then the ammonia was allowed to
evaporate. The pale yellow residue was partitioned between CH2Cl2 (30 mL) and
water (40 mL). The layers were separated, and the aqueous layer was extracted
with CH2Cl2 (2 × 30 mL). The combined organic layers were washed with 10%
sodium thiosulfate solution (20 mL), dried over magnesium sulfate, and concentrated.
Flash chromatography (EtOAc:hexane, 2:1) on silica gave 2.21 g (75%) of the
tetrahydroisoquinolinone.??Reference: Schultz, A. G.; Guzi, T. J.; Larsson, E.; Rahm, R.; Thakker, K.
Bidlack, J. M. J. Org. Chem. 1998, 63, 7795–7804.
Reference
https://www.alfa.com/en/catalog/L08143/
https://www.ncbi.nlm.nih.gov/pubmed/21235510
https://en.wikipedia.org/wiki/Tetrahydroisoquinoline
Okuda, K, Y. Kotake, and S. Ohta. "Parkinsonism-preventing activity of 1-methyl-1, 2, 3, 4-tetrahydroisoquinoline derivatives in C57BL mouse in vivo. Biological & Pharmaceutical Bulletin 29.7(2006):1401-1403.
Luca, Laura De, et al. "3D Pharmacophore Models for 1, 2, 3, 4‐Tetrahydroisoquinoline Derivatives Acting as Anticonvulsant Agents." Archiv Der Pharmazie 339.7(2006):388-400.
Hatano, H, et al. "Tumor-specific cytotoxic activity of 1, 2, 3, 4-tetrahydroisoquinoline derivatives against human oral squamous cell carcinoma cell lines."Anticancer Research 29.8(2009):3079-3086.
Synthesis Reference(s)
The Journal of Organic Chemistry, 40, p. 1191, 1975 DOI: 10.1021/jo00897a001Tetrahedron Letters, 26, p. 4633, 1985 DOI: 10.1016/S0040-4039(00)98771-9
Check Digit Verification of cas no
The CAS Registry Mumber 91-21-4 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 9 and 1 respectively; the second part has 2 digits, 2 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 91-21:
(4*9)+(3*1)+(2*2)+(1*1)=44
44 % 10 = 4
So 91-21-4 is a valid CAS Registry Number.
InChI:InChI=1/C9H11N/c1-2-4-9-7-10-6-5-8(9)3-1/h1-4,10H,5-7H2/p+1
91-21-4Relevant articles and documents
Engineering of Thermostable β-Hydroxyacid Dehydrogenase for the Asymmetric Reduction of Imines
Stockinger, Peter,Schelle, Luca,Schober, Benedikt,Buchholz, Patrick C. F.,Pleiss, Jürgen,Nestl, Bettina M.
, p. 3511 - 3514 (2020)
The β-hydroxyacid dehydrogenase from Thermocrinus albus (Ta-βHAD), which catalyzes the NADP+-dependent oxidation of β-hydroxyacids, was engineered to accept imines as substrates. The catalytic activity of the proton-donor variant K189D was further increased by the introduction of two nonpolar flanking residues (N192 L, N193 L). Engineering the putative alternative proton donor (D258S) and the gate-keeping residue (F250 A) led to a switched substrate specificity as compared to the single and triple variants. The two most active Ta-βHAD variants were applied to biocatalytic asymmetric reductions of imines at elevated temperatures and enabled enhanced product formation at a reaction temperature of 50 °C.
carba Nicotinamide Adenine Dinucleotide Phosphate: Robust Cofactor for Redox Biocatalysis
D?ring, Manuel,Sieber, Volker,Simon, Robert C.,Tafertshofer, Georg,Zachos, Ioannis
supporting information, p. 14701 - 14706 (2021/05/13)
Here we report a new robust nicotinamide dinucleotide phosphate cofactor analog (carba-NADP+) and its acceptance by many enzymes in the class of oxidoreductases. Replacing one ribose oxygen with a methylene group of the natural NADP+ was found to enhance stability dramatically. Decomposition experiments at moderate and high temperatures with the cofactors showed a drastic increase in half-life time at elevated temperatures since it significantly disfavors hydrolysis of the pyridinium-N?glycoside bond. Overall, more than 27 different oxidoreductases were successfully tested, and a thorough analytical characterization and comparison is given. The cofactor carba-NADP+ opens up the field of redox-biocatalysis under harsh conditions.
Homogeneous pressure hydrogenation of quinolines effected by a bench-stable tungsten-based pre-catalyst
Heizinger, Christian,Topf, Christoph,Vielhaber, Thomas
, p. 451 - 461 (2021/11/11)
We report on an operationally simple catalytic method for the tungsten-catalyzed hydrogenation of quinolines through the use of the easily handled and self-contained precursor [WCl(η5-Cp)(CO)3]. This half sandwich complex is indefinitely storable on the bench in simple screw-capped bottles or stoppered flasks and can, if required, be prepared on a multi-gram scale while the actual catalytic transformations were performed in the presence of a Lewis acid in order to achieve both decent substrate conversions and product yields. The described method represents a facile and atom-efficient access to a variety of 1,2,3,4-tetrahydroquinolines that circumvents the use of cost-intensive and oxygen-sensitive phosphine ligands as well as auxiliary hydride reagents.