CN105884768A - Method for preparing 1-substituted-beta-carboline-3-carboxylic ester - Google Patents
Method for preparing 1-substituted-beta-carboline-3-carboxylic ester Download PDFInfo
- Publication number
- CN105884768A CN105884768A CN201610077168.1A CN201610077168A CN105884768A CN 105884768 A CN105884768 A CN 105884768A CN 201610077168 A CN201610077168 A CN 201610077168A CN 105884768 A CN105884768 A CN 105884768A
- Authority
- CN
- China
- Prior art keywords
- carboline
- carboxylate
- replacement
- preparation
- nano
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/20—Spiro-condensed systems
Abstract
The invention discloses a method for preparing 1-substituted-beta-carboline-3-carboxylic ester. Methyl tryptophan and aromatic aldehyde or a carbonyl containing cyclic compound and a catalyst are added into a solvent, separation and purification are carried out after a heating reaction, and 1-substituted-beta-carboline-3-carboxylic ester is obtained. A 1-substituted-beta-carboline-3-carboxylic ester derivative is synthesized through a one-step method with high yield. The defects that in a current synthesis reaction, a poisonous catalyst and a poisonous solvent are adopted, the reaction temperature is high, the steps are complex, and the yield is not ideal are avoided.
Description
Technical field
The invention belongs to chemistry or field of pharmaceutical chemistry technology, be specifically related to the preparation method of a kind of 1-replacement-B-carboline-3-carboxylate.
Background technology
B-carboline structure (shown in formula I) is the part of nitrogenous indoles alkaloid, is natural and the elementary cell of synthetic drug.This compounds has biochemistry and pharmacological activity, such as anti-malarial widely, antitumor, AntiHIV1 RT activity, antianxiety, calm etc..B-carboline-3-carboxylate compound (shown in formula II) is as a kind of important pharmaceutical intermediate, its synthesis receives significant attention, the synthesis of existing B-carboline-3-carboxylic acid ester compound is all that precursor is at isopropylbenzene or reflux in toluene oxidative synthesis β carboline compounds with 4-(H)-B-carboline-3-carboxylate, used catalyst has: palladium supporting carbon catalyst, sulphur, SeO2Or MnO2Tetrachloroquinone; DDQ (DDQ); sym-closene (TCCA), repefral (DMP), iodosobenzoic acid (IBX) etc.; it is big with solvent toxicity to there is catalyst, oxidant in these synthetic methods; oxidizing reaction temperature is higher, and step is complicated, and productivity is undesirable waits many problems.Therefore, develop the synthetic method of a kind of succinct high effective green environmentally friendly, be to need the urgent technical barrier solved.
Summary of the invention
It is an object of the invention to provide the preparation method of a kind of 1-replacement-B-carboline-3-carboxylate, with the defect overcoming above-mentioned prior art to exist, the present invention uses one-step method high yield synthesis 1-to replace B-carboline-3-carboxylic ester derivative.Avoid catalyst poisonous in current synthetic reaction, toxic solvent, high reaction temperature, the defect that step complexity productivity is undesirable.
For reaching above-mentioned purpose, the present invention adopts the following technical scheme that
A kind of preparation method of 1-replacement-B-carboline-3-carboxylate, add in solvent the tryptophan methyl ester as shown in formula III and the aromatic aldehyde as shown in formula IV or as shown in formula V containing carbonyl cyclic compound, and catalyst, add separating-purifying after thermal response completes and i.e. obtain the 1-replacement-B-carboline-3-carboxylate as shown in formula VI or formula VII；
Wherein, R1For with the aryl of substituent or heteroaryl.
Further, the substituent of described aryl or heteroaryl is H, C1-C6Alkyl, C1-C6Alkoxyl, aldehyde radical or halogen.
Further, described aryl is phenyl or naphthyl；Described heteroaryl is furyl, pyridine radicals, piperidyl, pyrrole radicals, thienyl, pyrazolyl, thiazolyl or piperazinyl.
Further, described is cyclohexanone containing carbonyl cyclic compound, acenaphthenequinone, replaces acenaphthenequinone, Fluorenone or replacement Fluorenone.
Further, described catalyst is nano-metal-oxide, and described nano-metal-oxide is the combination of one or more of nano cupric oxide, nano-cerium oxide, nano ferriferrous oxide, nano-titanium oxide.
Further, described solvent is ethanol and the mixture of water or methyl alcohol with water, and wherein ethanol or methyl alcohol are 1:(0.2～5 with the volume ratio of water).
Further, tryptophan methyl ester is 1:(1.1～1.2 with the ratio of aromatic aldehyde or the amount of the material containing carbonyl cyclic compound).
Further, tryptophan methyl ester is 1:(0.002～0.5 with the ratio of the amount of the material of catalyst).
Further, the temperature adding thermal response is 40-75 DEG C, and the reaction time is 1-30h.
A kind of preparation method of 1-replacement-B-carboline-3-carboxylate, the tryptophan methyl ester as shown in formula III and the isatin as shown in formula VIII is added in solvent, and nano cupric oxide is as catalyst, after being heated to reflux 6h at a temperature of 75 DEG C, separating-purifying i.e. obtains the 1-replacement-B-carboline-3-carboxylate as shown in formula Ⅸ；
Wherein, tryptophan methyl ester is 1:1.1 with the ratio of the amount of the material of isatin, and tryptophan methyl ester is 1:0.009 with the ratio of the amount of the material of catalyst；
Solvent is ethanol and the mixture of water or methyl alcohol with water, and the volume ratio of ethanol or methyl alcohol and water is 3:1, when solvent is ethanol with the mixture of water, and R2For ethyl；When the mixture that solvent is methyl alcohol and water, R2For methyl.
Compared with prior art, the present invention has a following useful technique effect:
The present invention uses one-step method to complete the composition of aromatic ring, being directly generated B-carboline compounds by tryptophan methyl ester with aromatic aldehyde or the cyclic compound Han carbonyl, the most efficiently, raw material is readily obtained, additionally use nontoxic non-all to catalyst participation reaction, productivity is high, it is not necessary to adding other oxidant, preparation method is simple, avoid catalyst poisonous in current synthetic reaction, toxic solvent, high reaction temperature, the defect that step complexity productivity is undesirable.
Further, the present invention uses green solvent water or methanol/ethanol, convenient post-treatment, does not cause environmental pollution.
Further, reaction temperature is 40-75 DEG C, less than existing a lot of method for oxidation, energy-saving safe.
Accompanying drawing explanation
Fig. 1 is the product prepared by embodiment 11H NMR spectra；
Fig. 2 is the product prepared by embodiment 113C NMR spectra；
Fig. 3 is the product prepared by embodiment 21H NMR spectra；
Fig. 4 is the product prepared by embodiment 213C NMR spectra；
Fig. 5 is the product prepared by embodiment 31H NMR spectra；
Fig. 6 is the product prepared by embodiment 313C NMR spectra；
Fig. 7 is the product prepared by embodiment 41H NMR spectra；
Fig. 8 is the product prepared by embodiment 413C NMR spectra；
Fig. 9 is the product prepared by embodiment 51H NMR spectra；
Figure 10 is the product prepared by embodiment 513C NMR spectra；
Figure 11 is the product prepared by embodiment 61H NMR spectra；
Figure 12 is the product prepared by embodiment 613C NMR spectra；
Figure 13 is the product prepared by embodiment 71H NMR spectra；
Figure 14 is the product prepared by embodiment 713C NMR spectra；
Figure 15 is the product prepared by embodiment 81H NMR spectra；
Figure 16 is the product prepared by embodiment 91H NMR spectra；
Figure 17 is the product prepared by embodiment 913C NMR spectra；
Figure 18 is the product prepared by embodiment 101H NMR spectra；
Figure 19 is the product prepared by embodiment 1013C NMR spectra；
Figure 20 is the product prepared by embodiment 111H NMR spectra；
Figure 21 is the product prepared by embodiment 1113C NMR spectra.
Detailed description of the invention
Below embodiments of the present invention are described in further detail:
A kind of preparation method of 1-replacement-B-carboline-3-carboxylate, add in solvent the tryptophan methyl ester as shown in formula III and the aromatic aldehyde as shown in formula IV or as shown in formula V containing carbonyl cyclic compound, wherein, tryptophan methyl ester is 1:(1.1～1.2 with the ratio of aromatic aldehyde or the amount of the material containing carbonyl cyclic compound), and catalyst, described catalyst is nano-metal-oxide, described nano-metal-oxide is nano cupric oxide, nano-cerium oxide, nano ferriferrous oxide, the combination of one or more of nano-titanium oxide, and the ratio of tryptophan methyl ester and the amount of the material of catalyst is 1:(0.002～0.5), after adding thermal response 1-30h at 40-75 DEG C, separating-purifying i.e. obtains the 1-replacement-B-carboline-3-carboxylate as shown in formula VI or formula VII；
Wherein, R1For with the aryl of substituent or heteroaryl, the substituent of described aryl or heteroaryl is H, C1-C6Alkyl, C1-C6Alkoxyl, aldehyde radical or halogen, C1-C6Alkyl refers to the straight or branched alkyl with 1-6 carbon atom, including C1Alkyl, C2Alkyl, C3Alkyl, C4Alkyl, C5Alkyl, C6Alkyl, C1-C6Alkoxyl refers to C1-C6Alkyl be connected with oxygen atom after group；Described aryl is phenyl or naphthyl；Described heteroaryl is furyl, pyridine radicals, piperidyl, pyrrole radicals, thienyl, pyrazolyl, thiazolyl or piperazinyl.
Described solvent is ethanol and the mixture of water or methyl alcohol with water, and wherein ethanol or methyl alcohol are 1:(0.2～5 with the volume ratio of water).
Described is cyclohexanone containing carbonyl cyclic compound, acenaphthenequinone, replaces acenaphthenequinone, Fluorenone or replacement Fluorenone.
A kind of preparation method of 1-replacement-B-carboline-3-carboxylate, the tryptophan methyl ester as shown in formula III and the isatin (belonging to containing carbonyl cyclic compound) as shown in formula VIII is added in solvent, and nano cupric oxide is as catalyst, after being heated to reflux 6h at a temperature of 75 DEG C, separating-purifying i.e. obtains the 1-replacement-B-carboline-3-carboxylate as shown in formula Ⅸ；
Wherein, tryptophan methyl ester is 1:1.1 with the ratio of the amount of the material of isatin, and tryptophan methyl ester is 1:0.009 with the ratio of the amount of the material of catalyst；
Solvent is ethanol and the mixture of water or methyl alcohol with water, and the volume ratio of ethanol or methyl alcohol and water is 3:1, when solvent is ethanol with the mixture of water, and R2For ethyl；When the mixture that solvent is methyl alcohol and water, R2For methyl.
Below in conjunction with embodiment, the present invention is described in further detail:
Embodiment 1
The preparation of 1-(4 '-methoxyl group) phenyl-B-carboline-3-carboxylate methyl ester
The tryptophan methyl ester of 2mmol is dissolved in the ethanol and water mixed liquid solvent that volume ratio is 1:2, add 2.1mmol P-methoxybenzal-dehyde, with the nano ferriferrous oxide of 0.004mmol nano cupric oxide and 0.004mmol as catalyst, it is heated to reflux at 75 DEG C 1 hour, with the carrying out of TLC monitoring reaction, concentrates after reaction completely, through column chromatography for separation, obtaining 265mg faint yellow solid, productivity is 89%, and structure of title compound formula is as follows:
As depicted in figs. 1 and 2, product nuclear-magnetism characterizes1H NMR(400MHz,CDCl3) δ 8.99 (s, 1H), 8.85 (s, 1H), 8.23 (d, J=7.9Hz, 1H), 7.87 (d, J=8.6Hz, 2H), 7.61 (t, J=11.8Hz, 2H), 7.43 7.33 (m, 1H), 7.01 (d, J=8.6Hz, 2H), 4.07 (s, 3H), 3.85 (s, 3H).13C NMR(101MHz,CDCl3)δ166.50,159.83,142.34,140.11,137.51,134.54,129.71,129.12,128.36,121.68,121.44,120.55,116.01,114.09,113.98,111.46,54.89,52.18.
Embodiment 2
The preparation of 1-(2 '-pyridine)-B-carboline-3-carboxylate methyl ester
The tryptophan methyl ester of 2mmol is dissolved in the methyl alcohol and water mixed liquid solvent that volume ratio is 5:1, add the two pyridine benzaldehydes of 2.4mmol, with 0.006mmol nano ferriferrous oxide as catalyst, it is heated to reflux at 40 DEG C 30 hours, with the carrying out of TLC monitoring reaction, concentrates after reaction completely, through column chromatography for separation, obtaining 515mg faint yellow solid, productivity is 86%, and structure of title compound formula is as follows:
As shown in Figure 3 and Figure 4, product nuclear-magnetism characterizes:1H NMR(400MHz,CDCl3) δ 11.67 (s, 1H), 8.96 8.91 (m, 2H), 8.83 (d, J=4.8Hz, 1H), 8.25 (d, J=7.8Hz, 1H), 8.00 7.95 (m, 1H), 7.71 (d, J=8.2Hz, 1H), 7.65 (t, J=7.3Hz, 1H), 7.44 7.38 (m, 2H), 4.12 (s, 3H).13C NMR(101MHz,CDCl3)δ166.24,156.53,147.72,140.50,137.07,136.69,136.15,135.66,130.18,128.51,123.10,121.62,121.40,120.98,120.33,117.81,111.83,52.18.
Embodiment 3
The preparation of 1-(4 '-pyridine)-B-carboline-3-carboxylate methyl ester
The tryptophan methyl ester of 2mmol is dissolved in the ethanol and water mixed liquid solvent that volume ratio is 1:5, add the two pyridine benzaldehydes of 2.2mmol, with 0.008mmol nano-cerium oxide as catalyst, it is heated to reflux at 50 DEG C 20 hours, with the carrying out of TLC monitoring reaction, concentrates after reaction completely, through column chromatography for separation, obtaining 500mg faint yellow solid, productivity is 84%, and structure of title compound formula is as follows:
As shown in Figure 5 and Figure 6, product nuclear-magnetism characterizes:1H NMR(400MHz,CDCl3) δ 9.74 (s, 1H), 8.95 (d, J=10.5Hz, 1H), 8.72 (d, J=5.5Hz, 2H), 8.26 (d, J=7.9Hz, 1H), 7.87 (d, J=5.8Hz, 2H), 7.74 7.58 (m, 2H), 7.47 7.39 (m, 1H), 4.08 (s, 3H).13C NMR(101MHz,CDCl3)δ166.04,149.85,145.12,140.54,139.19,137.86,134.81,130.21,129.02,122.65,121.60,121.36,121.01,117.55,111.68,52.37.
Embodiment 4
The preparation of 1-(2 '-furans)-B-carboline-3-carboxylate methyl ester
The tryptophan methyl ester of 2mmol is dissolved in the ethanol and water mixed liquid solvent that volume ratio is 1:3, add the furfural of 2.2mmol, with 0.009mmol nano-cerium oxide as catalyst, it is heated to reflux at 60 DEG C 10 hours, with the carrying out of TLC monitoring reaction, concentrates after reaction completely, through column chromatography for separation, obtaining 500mg faint yellow solid, productivity is 86%, and structure of title compound formula is as follows:
As shown in Figure 7 and Figure 8, product nuclear-magnetism characterizes:1H NMR(400MHz,CDCl3) δ 9.64 (s, 1H), 8.83 (s, 1H), 8.22 (d, J=7.8Hz, 1H), 7.77 (d, J=1.1Hz, 1H), 7.69 7.61 (m, 2H), 7.48 (d, J=3.4Hz, 1H), 7.42 7.37 (m, 1H), 6.71 (dd, J=3.5,1.8Hz, 1H), 4.09 (s, 3H).13C NMR(101MHz,CDCl3)δ163.98,142.68,140.13,132.79,132.33,129.80,128.61,125.93,121.85,121.42,121.12,120.61,116.09,111.99,111.46,109.69,52.18.
Embodiment 5
The preparation of 1-(4 '-isobutyl group) phenyl-B-carboline-3-carboxylate methyl ester
The tryptophan methyl ester of 2mmol is dissolved in the ethanol and water mixed liquid solvent that volume ratio is 1:5, add the cumal of 2.4mmol, with 0.012mmol nano-cerium oxide as catalyst, it is heated to reflux at 70 DEG C 14 hours, with the carrying out of TLC monitoring reaction, concentrates after reaction completely, through column chromatography for separation, obtaining 600mg faint yellow solid, productivity is 87%, and structure of title compound formula is as follows:
As shown in Figure 9 and Figure 10, product nuclear-magnetism characterizes:1H NMR(400MHz,CDCl3) δ 8.96 (s, 1H), 8.87 (s, 1H), 8.24 (d, J=7.9Hz, 1H), 7.84 (d, J=8.1Hz, 2H), 7.71 7.49 (m, 2H), 7.43 7.32 (m, 3H), 4.07 (s, 3H), 2.98 (dt, J=13.8,6.9Hz, 1H), 1.30 (s, 3H), 1.28 (s, 3H).13C NMR(101MHz,CDCl3)δ166.50,149.62,142.66,140.09,137.59,134.72,134.62,129.08,128.38,127.81,126.72,121.65,121.47,120.54,116.21,111.42,52.16,33.55,23.42.
Embodiment 6
The preparation of 1-(3 '-nitro) phenyl-B-carboline-3-carboxylate methyl ester
The tryptophan methyl ester of 2mmol is dissolved in the ethanol and water mixed liquid solvent that volume ratio is 4:1, add the 3-nitrobenzaldehyde of 2.2mmol, with 0.004mmol nano-titanium oxide as catalyst, it is heated to reflux at 75 DEG C 20 hours, with the carrying out of TLC monitoring reaction, concentrates after reaction completely, through column chromatography for separation, obtaining 558mg faint yellow solid, productivity is 79%, and structure of title compound formula is as follows:
As is illustrated by figs. 11 and 12, product nuclear-magnetism characterizes:1H NMR (400MHz, DMSO) δ 12.15 (s, 1H), 9.02 (s, 1H), 8.78 (s, 1H), 8.48 (d, J=7.8Hz, 2H), 8.43 (dd, J=8.0,1.8Hz, 1H), 7.95 (t, J=8.0Hz, 1H), 7.71 (d, J=8.2Hz, 1H), 7.65 (t, J=7.8Hz, 1H), 7.37 (t, J=7.1Hz, 1H), 3.96 (s, 3H).13C NMR(101MHz,DMSO)δ165.75,148.13,141.50,139.49,138.86,136.81,134.95,134.67,130.41,128.99,123.52,123.25,122.13,121.01,120.61,117.38,112.61,52.07,48.50.
Embodiment 7
The preparation of 1-spiral shell-indoles-2-ethyoxyl-B-carboline-3-carboxylate methyl ester
The tryptophan methyl ester of 2mmol is dissolved in the ethanol and water mixed liquid solvent that volume ratio is 3:1, add the isatin of 2.2mmol, with 0.018mmol nano cupric oxide as catalyst, it is heated to reflux at 75 DEG C 6 hours, with the carrying out of TLC monitoring reaction, concentrates after reaction completely, through column chromatography for separation, obtaining 505mg white solid, productivity is 65%, and structure of title compound formula is as follows:
As shown in Figure 13 and Figure 14, product nuclear-magnetism characterizes:1H NMR (400MHz, DMSO) δ 12.03 (s, 1H), 10.80 (s, 1H), 8.99 (s, 1H), 8.48 (d, J=7.9Hz, 1H), 8.19 (d, J=8.2Hz, 1H), 7.96 (dd, J=7.7,1.3Hz, 1H), 7.71 (d, J=8.2Hz, 1H), 7.63 (dd, J=11.7,4.5Hz, 1H), 7.56 (dd, J=11.4,4.3Hz, 1H), 7.40 7.27 (m, 2H), 4.05 (q, J=7.1Hz, 2H), 3.97 (s, 3H), 1.16 (t, J=7.1Hz, 3H).13C NMR(101MHz,DMSO)δ165.60,153.30,141.50,140.71,136.93,134.87,129.95,129.74,128.93,123.17,122.11,121.10,120.58,116.72,112.81,60.33,52.18,14.36.
Embodiment 8
The preparation of 1-spiral shell-indoles-2-methoxy-p-carboline-3-carboxylate methyl ester
The tryptophan methyl ester of 2mmol is dissolved in the methyl alcohol and water mixed liquid solvent that volume ratio is 3:1, add the isatin of 2.2mmol, with 0.018mmol nano cupric oxide as catalyst, 6 hours it are heated to reflux at 75 DEG C, carrying out with TLC monitoring reaction, concentrating after reaction completely, through column chromatography for separation, structure of title compound formula is as follows:
As shown in figure 15, product nucleus magnetic hydrogen spectrum characterizes1H NMR(400MHz,CDCl3) δ 10.45 (s, 1H), 9.67 (s, 1H), 8.91 (s, 1H), 8.27 (d, J=7.9Hz, 1H), 8.22 (d, J=7.5Hz, 1H), 7.81 (d, J=7.3Hz, 1H), 7.76 7.64 (m, 2H), 7.45 (t, J=7.5Hz, 2H), 7.27 (s, 1H), 4.12 (s, 3H), 3.70 (s, 3H).
Embodiment 9
The preparation of 1-ethenylphenyl-B-carboline-3-carboxylate methyl ester:
The tryptophan methyl ester of 2mmol is dissolved in the ethanol and water mixed liquid solvent that volume ratio is 1:3, add the cinnamic acid of 2.2mmol, with the nano ferriferrous oxide of 0.004mol nano-cerium oxide, the nano-titanium oxide of 0.004mol and 0.004mol as catalyst, it is heated to reflux at 75 DEG C 1 hour, with the carrying out of TLC monitoring reaction, concentrates after reaction completely, through column chromatography for separation, obtaining 452mg faint yellow solid, productivity is 69%, and structure of title compound formula is as follows:
As shown in Figure 16 and Figure 17, product nuclear-magnetism characterizes:1H NMR(400MHz,CDCl3) δ 8.88 (s, 1H), 8.81 (s, 1H), 8.22 (d, J=7.9Hz, 1H), 7.94 (d, J=7.1Hz, 2H), 7.61 (d, J=8.0Hz, 1H), 7.55 (dd, J=14.7,7.6Hz, 4H), 7.47 (t, J=7.3Hz, 1H), 7.38 (t, J=7.9Hz, 2H), 4.05 (s, 3H).13C NMR(101MHz,CDCl3)δ166.92,142.98,140.58,138.31,137.79,136.48,135.15,129.83,129.26,129.23,129.02,128.72,128.38,122.17,122.04,121.18,116.95,111.90,52.70.
Embodiment 10
The preparation of 1-(4 '-formyl-phenyl)-B-carboline-3-carboxylate methyl ester
The tryptophan methyl ester of 2mmol is dissolved in the ethanol and water mixed liquid solvent that volume ratio is 4:1, add the terephthalaldehyde of 2.2mmol, with 1mol nano cupric oxide as catalyst, it is heated to reflux at 50 DEG C 30 hours, with the carrying out of TLC monitoring reaction, concentrates after reaction completely, through column chromatography for separation, obtaining 0.561mg white solid, productivity is 85%, and structure of title compound formula is as follows:
As shown in Figure 18 and Figure 19, product nuclear-magnetism is characterized as:1H NMR (400MHz, DMSO) δ 12.09 (s, 1H), 12.09 (s, 1H), 10.19 (s, 1H), 10.19 (s, 1H), 9.01 (s, 1H), 9.01 (s, 1H), 8.48 (d, J=7.9Hz, 1H), 8.27 (d, J=8.2Hz, 2H), 8.19 (d, J=8.3Hz, 2H), 7.72 (d, J=8.2Hz, 1H), 7.67 7.60 (m, 1H), 7.41 7.33 (m, 1H), 3.96 (s, 3H).13C NMR(101MHz,DMSO)δ193.01,165.89,142.95,141.54,140.52,136.83,136.14,134.78,129.89,129.69,129.34,128.96,122.15,121.02,120.61,117.36,112.75,52.12.
Embodiment 11
The preparation of 1-spiral shell-acenaphthylene ketone group-B-carboline-3-carboxylate methyl ester
The tryptophan methyl ester of 2mmol is dissolved in the ethanol and water mixed liquid solvent that volume ratio is 4:1, add the acenaphthenequinone of 2.2mmol, with 1mmol nano cupric oxide as catalyst, it is heated to reflux at 75 DEG C 1 hour, with the carrying out of TLC monitoring reaction, concentrates after reaction completely, through column chromatography for separation, obtaining 463mg white solid, productivity is 61%, and structure of title compound formula is as follows:
As shown in Figure 20 and Figure 21, product nuclear-magnetism characterizes:1H NMR(400MHz,CDCl3) δ 9.24 (dd, J=7.6,1.3Hz, 1H), 8.97 (dd, J=7.6,1.4Hz, 1H), 8.90 (d, J=8.5Hz, 1H), 8.74 (s, 1H), 8.20 (d, J=7.9Hz, 2H), 8.07 (dd, J=8.0,1.1Hz, 1H), 7.80 (dd, J=7.3,4.5Hz, 1H), 7.78 7.73 (m, 1H), 7.69 (t, J=7.8Hz, 1H), 7.59 (t, J=7.2Hz, 1H), 4.13 (s, 3H).13C NMR(101MHz,DMSO)δ170.00,165.29,141.71,140.27,136.07,135.38,134.57,134.47,132.56,132.20,131.33,130.63,130.58,128.90,128.25,126.32,125.48,125.30,124.02,122.02,119.16,117.73,116.03,52.57。
Claims (10)
1. the preparation method of a 1-replacement-B-carboline-3-carboxylate, it is characterised in that add in solvent
Enter the tryptophan methyl ester as shown in formula III and the aromatic aldehyde as shown in formula IV or as shown in formula V containing carbonyl ring
Shape compound, and catalyst, add separating-purifying after thermal response completes and i.e. obtain as shown in formula VI or formula VII
1-replacement-B-carboline-3-carboxylate；
Wherein, R1For with the aryl of substituent or heteroaryl.
The preparation method of a kind of 1-replacement-B-carboline-3-carboxylate the most according to claim 1, its
Being characterised by, the substituent of described aryl or heteroaryl is H, C1-C6Alkyl, C1-C6Alkoxyl, aldehyde
Base or halogen.
The preparation method of a kind of 1-replacement-B-carboline-3-carboxylate the most according to claim 1, its
Being characterised by, described aryl is phenyl or naphthyl；Described heteroaryl be furyl, pyridine radicals, piperidyl,
Pyrrole radicals, thienyl, pyrazolyl, thiazolyl or piperazinyl.
The preparation method of a kind of 1-replacement-B-carboline-3-carboxylate the most according to claim 1, its
Being characterised by, described is cyclohexanone containing carbonyl cyclic compound, acenaphthenequinone, replaces acenaphthenequinone, Fluorenone or replacement
Fluorenone.
The preparation method of a kind of 1-replacement-B-carboline-3-carboxylate the most according to claim 1, its
Being characterised by, described catalyst is nano-metal-oxide, and described nano-metal-oxide is nano oxidized
Copper, nano-cerium oxide, nano ferriferrous oxide, the combination of one or more of nano-titanium oxide.
The preparation method of a kind of 1-replacement-B-carboline-3-carboxylate the most according to claim 1, its
Being characterised by, described solvent is ethanol and the mixture of water or methyl alcohol with water, wherein ethanol or methyl alcohol and water
Volume ratio be 1:(0.2～5).
The preparation method of a kind of 1-replacement-B-carboline-3-carboxylate the most according to claim 1, its
Being characterised by, tryptophan methyl ester is 1 with the ratio of aromatic aldehyde or the amount of the material containing carbonyl cyclic compound:
(1.1～1.2).
The preparation method of a kind of 1-replacement-B-carboline-3-carboxylate the most according to claim 1, its
Being characterised by, tryptophan methyl ester is 1:(0.002～0.5 with the ratio of the amount of the material of catalyst).
The preparation method of a kind of 1-replacement-B-carboline-3-carboxylate the most according to claim 1, its
Being characterised by, the temperature adding thermal response is 40-75 DEG C, and the reaction time is 1-30h.
10. the preparation method of a 1-replacement-B-carboline-3-carboxylate, it is characterised in that in solvent
Add the tryptophan methyl ester as shown in formula III and the isatin as shown in formula VIII, and nano cupric oxide is as urging
Agent, after being heated to reflux 6h at a temperature of 75 DEG C, separating-purifying i.e. obtains the 1-replacement-β as shown in formula Ⅸ
-carboline-3-carboxylate；
Wherein, tryptophan methyl ester is 1:1.1, tryptophan methyl ester and catalyst with the ratio of the amount of the material of isatin
The ratio of amount of material be 1:0.009；
Solvent is ethanol and the mixture of water or methyl alcohol with water, and the volume ratio of ethanol or methyl alcohol and water is
3:1, when the mixture that solvent is ethanol and water, R2For ethyl；When the mixture that solvent is methyl alcohol and water
Time, R2For methyl.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610077168.1A CN105884768B (en) | 2016-02-03 | 2016-02-03 | A kind of preparation method of the carboxylate of 1 substituted beta carboline 3 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610077168.1A CN105884768B (en) | 2016-02-03 | 2016-02-03 | A kind of preparation method of the carboxylate of 1 substituted beta carboline 3 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105884768A true CN105884768A (en) | 2016-08-24 |
| CN105884768B CN105884768B (en) | 2017-07-07 |
Family
ID=57013703
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610077168.1A Active CN105884768B (en) | 2016-02-03 | 2016-02-03 | A kind of preparation method of the carboxylate of 1 substituted beta carboline 3 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105884768B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106397434A (en) * | 2016-09-05 | 2017-02-15 | 清华大学 | Preparation method of 1-carbonyl-beta-carboline compound |
| CN109134460A (en) * | 2018-08-02 | 2019-01-04 | 南开大学 | A kind of synthetic method of B-carboline class compound |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008103470A2 (en) * | 2007-02-21 | 2008-08-28 | Trustees Of Columbia University In The City Of New York | Oncogenic-ras-signal dependent lethal compounds |
| CN103130800A (en) * | 2011-12-05 | 2013-06-05 | 上海药明康德新药开发有限公司 | 1,3,6,9-substitution beta-carboline compound and preparation method thereof |
-
2016
- 2016-02-03 CN CN201610077168.1A patent/CN105884768B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008103470A2 (en) * | 2007-02-21 | 2008-08-28 | Trustees Of Columbia University In The City Of New York | Oncogenic-ras-signal dependent lethal compounds |
| CN103130800A (en) * | 2011-12-05 | 2013-06-05 | 上海药明康德新药开发有限公司 | 1,3,6,9-substitution beta-carboline compound and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| DALIA S. EL-GAMIL ET AL.: ""Design of Novel β-Carboline Derivatives with Pendant 5-Bromothienyl and Their Evaluation as Phosphodiesterase-5 Inhibitors"", 《ARCH. PHARM. CHEM. LIFE SCI》 * |
| WEN CAI ET AL.: ""Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents"", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106397434A (en) * | 2016-09-05 | 2017-02-15 | 清华大学 | Preparation method of 1-carbonyl-beta-carboline compound |
| CN106397434B (en) * | 2016-09-05 | 2018-02-09 | 清华大学 | The preparation method of 1 carbonyl β carboline class compounds |
| CN109134460A (en) * | 2018-08-02 | 2019-01-04 | 南开大学 | A kind of synthetic method of B-carboline class compound |
| CN109134460B (en) * | 2018-08-02 | 2021-04-06 | 南开大学 | Synthesis method of beta-carboline compound |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105884768B (en) | 2017-07-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Paul et al. | An efficient green protocol for the synthesis of coumarin fused highly decorated indenodihydropyridyl and dihydropyridyl derivatives | |
| CN106928215A (en) | A kind of preparation method of Quinolizinone type compounds | |
| Cheng et al. | Intramolecular cross dehydrogenative coupling of 4-substituted coumarins: rapid and efficient access to coumestans and indole [3, 2-c] coumarins | |
| CN114031542A (en) | Novel preparation method of azabicyclo medical intermediate | |
| Khalafy et al. | A Green, Organometallic Catalyzed Synthesis of a Series of Novel Functionalized 4‐Aroyl‐4H‐benzo [g] chromenes through One‐pot, Three Component Reaction | |
| Flader et al. | Brønsted acid mediated synthesis and properties of dibenzoacridine derivatives | |
| Obydennov et al. | An improved synthesis and some reactions of diethyl 4-oxo-4H-pyran-2, 5-dicarboxylate | |
| Zhang et al. | Three-component domino cyclization of novel carbazole and indole fused pyrano [2, 3-c] pyridine derivatives | |
| CN105884768A (en) | Method for preparing 1-substituted-beta-carboline-3-carboxylic ester | |
| Liu et al. | Copper-Catalyzed One-Pot Synthesis of 2, 3-Dihydroquinazolin-4 (1H)-ones from 2-Nitrobenzonitriles and Carbonyl Compounds Mediated by Diboronic Acid in Methanol–Water | |
| Sun et al. | Efficient synthesis of novel cyclic fused-phenothiazines via domino cyclization of 2-(benzo [b][1, 4] thiazin-3-ylidene) acetate, aromatic aldehydes and cyclic 1, 3-diketones | |
| Peschko et al. | Biomimetic syntheses of lamellarin and lukianol-type alkaloids | |
| Thirumurugan et al. | A simple one-pot synthesis of functionalised 6-(indol-3-yl)-2, 2′-bipyridine derivatives via multi-component reaction under neat condition | |
| Moghaddam et al. | The stereoselective synthesis of tetrahydrothiopyrano [2, 3-b] indole skeletons via tandem reaction of indoline-2-thiones to Baylis–Hillman adduct acetates | |
| CN110357805B (en) | Preparation method of N-methyl-3-phenylseleno maleimide compound | |
| Gürtler et al. | [4+ 2]-cycloaddition reactions between β-acceptor-substituted enamines and 2-vinylindole radical cations acting as hetero-dienes | |
| Sun et al. | Selective construction of indeno [1, 2-b] phenothiazine and indeno [2, 1-c] phenothiazine via tandem annulation reaction | |
| Duan et al. | Convenient one-pot three-component synthesis of trifluoromethylated tetrahydrobenzo [g] chromene derivatives | |
| CN111471046A (en) | Carbazole indoquinone derivative and preparation method and application thereof | |
| Bulumulla et al. | π-spacer-linked bisthienopyrroles with tunable optical properties | |
| Jana et al. | Lateral Lithiation-Initiated Annulations in the Synthesis of 1-Oxygenated Carbazole Alkaloids and a Cycloheptacarbazole | |
| Mohammed et al. | Synthesis and spectral characterization of 1, 5-naphthyridine derivatives through cross-coupling Suzuki reaction | |
| Verma et al. | Piperidine-mediated annulation of 2-acylphenols with 4-nitrobenzaldehyde to 3-benzofuranones | |
| CN106117247B (en) | A kind of preparation method of the cyclohexadione compounds of 2 methyl 1,2,3,9 tetrahydro benzo [b] pyrroles [1,4] thiazine 1,3 | |
| Wakchaure et al. | Intramolecular chemoselective acylation of a suitably substituted isoindole: synthesis of (±)-chilenine and (±)-deoxychilenine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |