13063-04-2 Usage
Description
This quaternary alkaloid occurs primarily in Zanthoxylum nitidum (Lam.) DC
but has also been found in several species of Fagara. It is normally isolated as the
chloride which forms bright yellow needles when recrystallized from EtOH-HCl.
The crystals decompose on heating to 240°C yielding a product having m.p.
285-6°C. The iodide also forms yellow needles and undergoes a similar trans_x0002_formation at the same temperature to yield a product with the same melting point, possibly identical to that obtained from the chloride. The crystalline
acetate, m.p. 255-260°C and the pseudocyanide, m.p. 215-6°C and decomposing completely at 234°C in vacuo have also been prepared. A periodide, which
fonns chocolate-brown needles when crystallized from Me2CO, m.p. 300-1 °c
(dec.) is useful for characterizing the base.
Preparation
A solution of 1555 (0.102 g, 0.278 mmol) and triphosgene (0.179 g, 0.602 mmol) in acetonitrile (2.5 mL) was stirred at 60 C° (bath temperature) for 0.5 h. After the addition of ice/water, a yellow precipitate was collected by filtration and recrystallized from ethanol/diethyl ether to directly afford nitidine chloride (0.098 g, 91%); mp 285–292 C°.
An isocyano group can serve as both a protecting group for the amino function, and, due to its electronic effect, as an activating group as well. These two functionalities are employed in a synthetic route whereby an amino function has to be protected and a condensation reaction is performed at the a-carbon atom, for which activation is required.
3,4-Fused tryptophan analogues 1563 and 1564 contain a ring that bridges the a-carbon and the 4-position of the indole ring, thus limiting the conformational flexibility of the side chain. The synthesis proceeds from N-formylated 40-bromotryptophan 1558 via isocyanide 1559, 2-propenoate 1560, and Pd-catalyzed cyclization of the a-2-propenyl dl-tryptophan derivatives 1561 and 1562 to give both the seven- and eight-membered constrained ring analogues 1564 and 1563. Dehydration of the formamide 1558 with triphosgene affords the isocyanide 1559 in 75% (87%) yield.
Biochem/physiol Actions
Nitidine chloride is a natural product with anti-cancer activity. Its mechanism of action likely involves several pathways. Nitidine chloride has been found to inhibit topoisomerase I and topoisomerase II, induce cell apoptosis by activation of the caspase-dependent pathway, suppress c-Src/FAK associated signaling pathways and suppress Janus kinase 2/STAT3 signaling and the expression of STAT3-dependent target genes, including cyclin D1, Bcl-xL, and VEGF. Nitidine chloride has also been found to have anti-malaria activity.
References
Arthur, Hui, Ng., Chern. Ind., 1514 (1958)Arthur, Hui, Ng.,J. Chern. Soc., 1840 (1959)Kuck, Albonico, Deulofeu., Chern. Ind., 945 (1966)
Check Digit Verification of cas no
The CAS Registry Mumber 13063-04-2 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,3,0,6 and 3 respectively; the second part has 2 digits, 0 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 13063-04:
(7*1)+(6*3)+(5*0)+(4*6)+(3*3)+(2*0)+(1*4)=62
62 % 10 = 2
So 13063-04-2 is a valid CAS Registry Number.
InChI:InChI=1/C21H19NO4/c1-22-10-13-7-17(23-2)18(24-3)8-15(13)14-5-4-12-6-19-20(26-11-25-19)9-16(12)21(14)22/h4-10,18H,11H2,1-3H3
13063-04-2Relevant articles and documents
A combined pathway for the synthesis of nitidine family alkaloids
Pallikonda, Gangaram,Hsieh, Chang-Yu,Su, Haw-Lih,Hsieh, Jen-Chieh
, p. 5399 - 5407 (2019)
Three related alkaloids, oxynitidine, nitidine and 5,6-dihydronitidine, have been afforded by the new synthetic protocols. In this approach, the Ni-catalyzed annulation reaction is indicated as the key step to construct the isoquinolinone core structure. The subsequent transformations lead to the target alkaloids.
Compounds from Toddalia asiatica: Immunosuppressant Activity and Absolute Configurations
Reinhardt, Jakob K.,Zimmermann-Klemd, Amy M.,Danton, Ombeline,Smie?ko, Martin,Gründemann, Carsten,Hamburger, Matthias
, p. 3012 - 3020 (2020)
In a screening of an extract library from plants used in Traditional Chinese Medicine the MeOH extract of Toddalia asiatica inhibited proliferation of human primary T cells with an IC50 of 25.8 μg/mL. Activity in the extract was tracked by HPLC activity profiling, and a total of 15 compounds were characterized. Three compounds, toddalic acid (6) and both enantiomers (7a and 7b) of toddanolic acid (7), were new natural products, and two recently published compounds, (2′R)-toddalolactone 3′-O-β-d-glucopyranoside (10) and (2′S)-toddalolactone 2′-O-β-d-glucopyranoside (11), were described in detail for the first time. The absolute configurations of compounds 8, 9, 10, 12, 13, and 15 were determined by comparison of experimental and calculated ECD spectra. For glucosides 9 and 10, ECD data and chiral-phase HPLC of the aglycones after enzymatic hydrolysis confirmed the results. Nitidine chloride (4) inhibited proliferation of primary human T cells with an IC50 of 0.4 μM.
A chlorinated nitidine synthesis method
-
, (2017/07/01)
The invention discloses a synthetic method of nitidine chloride. The synthetic method comprises the following steps: 1) dissolving 3,4-dimethoxybenzoic acid in a first organic solvent, adding thionyl chloride to react, evaporating out the solvent from reactants to obtain an intermediate 1; 2) dissolving the intermediate 1 by use of the first organic solvent, adding 3,4-methylenedioxy naphthylamine, and performing nucleophilic substitution reaction to obtain an intermediate 2; 3) dissolving the intermediate 2 in the first organic solvent, adding boron trifluoride diethyl etherate and di(trifluoroacetoxyl) iodobenzene to react, removing the solvent from the reactants, performing column chromatography on obtained residues on silica gel to obtain an intermediate 3; 4) dissolving the intermediate 3 in a second organic solvent, and performing lithium aluminum hydride reduction, dehydration and dimethyl sulfate methylation under an atmosphere protection condition, and then treating with sodium chloride to obtain the target product nitidine chloride. The synthetic method disclosed by the invention is relatively simple in synthesis route and relatively high in yield of the target product and the yield is higher than 27%.
