3323-73-7Relevant academic research and scientific papers
New photosensitive polymers: Synthesis and free radical polymerization of oxypyridinium and oxyisoquinolinium functionalized methacrylate and styrene derivatives
Goertz, Verena,Ritter, Helmut
, p. 4258 - 4265 (2002)
Polymerizable hydroxypyridinium and hydroxyisoquinolinium salts 1a-4a, 2d, and 3d have been prepared from vinylbenzyl chloride or glycidyl methacrylate and 3-hydroxypyridine (2), 4- or 5-hydroxyisoquinoline (1, 3), and 8-hydroxyquinoline (4). Radical homo- and copolymerization with styrene or methyl methacrylate of the salts 1a-3a, 2d, and 3d produced (co)polymers 1e, 2e, 2f, 3f, 1g, 2g, 2h, and 3h. The photosensitive dipolar oxypyridinium or oxyisochinolinium betaine structures were generated in solutions with triethylamine from the low molecular weight and polymeric salt precursors. For the model compounds 1b-4b and (co)polymers 1e, 2e, 2f, 3f, 1g, 2g, 2h, and 3h, the degradation of the longest wavelength absorption of this betaine structure was detected during UV irradiation. UV irradiation of the model compound N-benzyl-4-hydroxyisochinolinium chloride (1b) in the presence of triethylamine produced the expected aziridine type structure 1k by intramolecular cyclization.
Synthesis and biological evaluation of isofebrifugine analogues
Zhang, Jinjin,Huang, Baohua,Lu, Yujing,Li, Wenbin,Zhuang, Zichong,Ke, Donghua,Zhong, Jingpeng,Zhou, Jinlin,Chen, Qian
, p. 1004 - 1010 (2019/11/22)
Isofebrifugine, as a kind of natural quinazolinone alkaloid with important physiological activities and good pharmacological effects, was isolated from a Chinese medicinal plant, Chang Shan (Dichroa febrifuga). In this paper, the synthesis of a series of novel isofebrifugine analogues was accomplished by employing the N-alkylation of 4(3H)-quinazolinones with benzyl (3aR,7aR)-rel-2-(bromomethyl)hexahydrofuro[3,2-b]pyridine-4(2H)carboxylates and the subsequent N-deprotection. These analogues were characterized by1 H NMR,13 C NMR and HRMS spectra. The MTT assay was used to examine the inhibitory effects of these analogues on the growth of human hepatoma cells (HepG2). The results indicated that some halogenated or hemiketal analogues showed interesting inhibition activity.
A benidipine hydrochloride method for synthesizing intermediate
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Paragraph 0030-0031; 0034, (2018/07/30)
The invention discloses a synthetic method for a benidipine hydrochloride intermediate. The synthetic method comprises performing a nucleophilic substitution reaction on 3-hydroxypyridine and a benzyl halide under a solvent refluxing condition, so as to generate 1-benzyl-3-hydroxypyridiniumhalide; taking an alcohol as a solvent and reducing 1-benzyl-3-hydroxypyridiniumhalide to generate 1-benzyl-3-piperidinol; then performing transesterification reaction on 1-benzyl-3-piperidinol and ethyl acetoacetate under a refluxing condition by taking toluene as a solvent in the presence/absence of a catalyst, and under the condition that less than 30% of the alcohol is left, performing normal-pressure distillation until the alcohol completely finishes reaction, so as to obtain the product. The synthetic method is simple and has the three-step total yield of 80% or more, and all employed materials are industrialized products and are cheap and easily obtained, and the quality is easily controlled.
Metabolites of febrifugine and its synthetic analogue by mouse liver S9 and their antimalarial activity against Plasmodium malaria parasite
Hirai, Shingo,Kikuchi, Haruhisa,Kim, Hye-Sook,Begum, Khurshida,Wataya, Yusuke,Tasaka, Hidehisa,Miyazawa, Yuriko,Yamamoto, Keisuke,Oshima, Yoshiteru
, p. 4351 - 4359 (2007/10/03)
Quinazolinone type alkaloids, febrifugine (1) and isofebrifugine (2), isolated from Dichroa febrifuga roots, show powerful antimalarial activity against Plasmodium falciparum. Unfortunately, their emetic effect and other undesirable side effects have precluded their clinical use for malaria. Because of their antimalarial potency, analogues were searched for, with the goal of preserving the strong antimalarial activity, while dramatically reducing side effects. We expected that compounds useful in drug development would exist in metabolites derived from 1 and Df-1 (3), the condensation product of 1 with acetone, by mouse liver S9. Feb-A and -B (4 and 5) were isolated as the major metabolites of 1. In addition to 4 and 5, feb-C and -D (6 and 7) were also purified from the metabolic mixture of 3. Compounds 4 and 5 were compounds oxidized at C-6 and C-2 of the quinazolinone ring of 1, respectively. Compounds 6 and 7, derived from 3, also bear febrifugine type structures in which the 4″- and 6″-positions of the piperidine ring of 1 were oxidized. In vitro antimalarial and cytotoxic tests using synthetically obtained racemic 4-6 and enantiomerically pure 7 demonstrated that 4 and 6 had antimalarial activity against P. falciparum, of similar potency to that of 1, with high selectivity. The antimalarial activity of 5 and 7, however, was dramatically decreased in the test. The in vitro antimalarial activity of analogues 22 and 43, which are stereoisomers of 4 and 6, was also evaluated, showing that 22 is active. The results suggest that basicity of both the 1- and the 1″-nitrogen atoms of 1 is crucial in conferring powerful antimalarial activity. Racemic 4 and 6 exhibited powerful in vivo antimalarial activity against mouse malaria P. berghei, and especially, no serious side effects were observed with 4. Thus, the metabolite 4 appears to be a promising lead compound for the development of new types of antimalarial drugs.
Synthesis of D/L-febrifugine and D/L-isofebrifugine
Takeuchi, Yasuo,Hattori, Mayumi,Abe, Hitoshi,Harayama, Takashi
, p. 1814 - 1818 (2007/10/03)
Racemic compounds (1 and 2) of the antimalarial agents febrifugine (D-1) and isofebrifugine (D-2) were synthesized using an unusual Claisen rearrangement of allyl enol ether 6 and the stereoselective reduction of 2- allylpiperid-3-one 8. This method is widely applicable to the synthesis of febirifugine derivatives.
Total synthesis of dl-febrifugine and dl-isofebrifugine
Takeuchi, Yasuo,Abe, Hitoshi,Harayama, Takashi
, p. 905 - 906 (2007/10/03)
Racemic compounds (1 and 2) of the antimalarial agents febrifugine (d- l) and isofebrifugine (d-2) were synthesized using an unusual Claisen rearrangement of allyl enol ether (7) and the stereoselective reduction of 2- allyl-3-piperidone (8). This method is widely applicable to the synthesis of derivatives needed to study the structure-activity relationship of febrifugine.
Methyl (S)-Lactate as a Chiral Auxiliary in the Asymmetric Synthesis of Bao Gong Teng A
Pham, Vinh C.,Charlton, James L.
, p. 8051 - 8055 (2007/10/03)
The asymmetric synthesis of Bao Gong Teng A, (-)-1, a natural product that shows strong antiglaucoma properties, is described.The synthesis begins with an asymmetric 1,3-dipolar cycloaddition of the acrylate of methyl (S)-lactate to the betaine of N-benzyl-3-hydroxypyridinium chloride giving cycloadduct 5a as a major product.The crude cycloadduct was reduced by catalytic hydrogenation to produce 6 in 61percent yield.The ketone 6 was reduced with LiAl(OtBu)3H to give exo alcohol 7b in 62percent yield.Protection of the alcohol group followed by replacement of the benzyl group on the nitrogen with a Boc group gave 12, which was then hydrolyzed to the acid 13 in 91percent yield for the three steps.The acid 13 was converted to the ketone 14 in 82percent yield via the acid chloride.Baeyer-Villiger oxidation converted 14 to 15 in 52percent yield.Optically pure Bao Gong Teng A was obtained in 9percent overall yield by the removal of both the Boc and the TBDMS groups using 1percent HCl - EtOH.
Kinetics of Benzylation of Hydroxypyridines & Hydroxyquinolines in Dimethyl Sulphoxide - Water & Isopropanol - Water Mixtures
Rajasekar, N.,Srinivasan, V. S.,Venkatasubramanian, N.
, p. 800 - 802 (2007/10/02)
The kinetics of benzylation of hydroxypyridines and hydroxyquinolines have been investigated in DMSO-water and isopropanol-water mixtures.A formal comparison of rate of benzylation of phenols and naphthols has also been made.DMSO, being a dipolar aprotic solvent facilitates O-alkylation of phenols and naphthols and a considerable rate increase has been observed in DMSO-water, giving the O-alkylated products in more than 90percent yield in both the cases.However, in the case of benzylation of hydroxypyridine in DMSO-water, O-alkylated product formed is only 65percent and the magnitude of rate increase, compared to phenols and naphthols, is much less, under similar conditions.But the rate of benzylation of 8-hydroxyquinoline in DMSO-water is retarded considerably and the rate is even slower than the rate of N-benzylation of quinoline, indicating only O-benzylation of 8-hydroxyquinoline in DMSO-water is unique and is mainly due to greater ground state solvation of substrate by DMSO, a factor which has been considered insignificant in all the other cases.
