CN111925326B - Selenoisonone compound and preparation method and application thereof - Google Patents
Selenoisonone compound and preparation method and application thereof Download PDFInfo
- Publication number
- CN111925326B CN111925326B CN202010966459.2A CN202010966459A CN111925326B CN 111925326 B CN111925326 B CN 111925326B CN 202010966459 A CN202010966459 A CN 202010966459A CN 111925326 B CN111925326 B CN 111925326B
- Authority
- CN
- China
- Prior art keywords
- compound
- electrode
- methyl
- phenyl
- preparation
- 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.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/58—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing atoms other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur or phosphorus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
- C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
- C25B3/00—Electrolytic production of organic compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Electrochemistry (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Metallurgy (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the field of organic synthesis, and in particular relates to a selenoisonone compound and a preparation method and application thereof. The invention generates functional isoquinolone compounds by electrochemical anodic oxidation of N-alkyl isoquinolone salt, and utilizes electrochemical reaction to construct C ═ O and C-Se bonds. The method has the advantages of good regioselectivity, high yield, novelty and environmental friendliness, and has wide application prospect in the preparation of natural products and medicines.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to the field of electrochemical synthesis, and more particularly relates to a selenoisonone compound and a preparation method and application thereof.
Background
Isoquinolones are important components of organic compounds, and their characteristic structures are widely present in natural products, drugs and bioactive compounds1-3. Isoquinolinone derivatives as NK3Of melatonin MT1Agonists of receptor and inhibitors of Rho-kinase4-6. In addition, they have powerful physiological functions, including antidepressant, antiulcer, antihypertensive, and asthma and tumor treatment7-11. Therefore, the construction of isoquinolone derivatives has been the direction of people's efforts. Using terminal oxidizing agents K3Fe(CN)6The direct oxidation preparation of isoquinoline salt is an important method for synthesizing isoquinoline salt12-14. However, these methods usually require the use of expensive or harmful oxidizing agents, which makes the whole preparation process cumbersome and costly15-21。
The organic selenium compound has important significance in the pharmaceutical industry, material science and synthetic chemistry30-36. In particular, recent studies have shown that N-heterocyclic molecules with seleno substituents possess unique biological and chemical properties37-40. At present, the related reports of the preparation method of the selenizing isoquinolone are less. Zhu you quan, etc41Use of isoquinolones and aryldiselenides in AgSbF6Under the mediation, dichloroethane is used as a solvent, and aryl selenium is introduced into the position C4 of the isoquinolone at 110 ℃, but the reaction temperature of the method is high, and the solvent and the catalyst are not environment-friendly. There is no doubt that the development of a green synthetic approach to introduce a seleno group into a heterocycle is highly desirable.
Organic electrochemistry is now an increasingly important topic22-26. Since the oxidizing agent and the reducing agent can be replaced with a constant current, the electrochemical method can be a reliable alternative to the conventional method27-29. While it is a potential alternative, it represents a clean and more sustainable transition.
At present, the reports of the selenoisonone compound are less, the activity of the compound is not reported in the related technology, and the related technology does not report a preparation method for directly obtaining the selenoisonone from the N-alkyl isoquinolone in one step.
Reference to the literature
(1)G.R.Pettit,V.Gaddamidi,G.M.Cragg,D.L.Herald and Y.Sagawa,J.Chem.Soc.,Chem.Commun.,1984,0,1693-1694.
(2)G.R.Pettit,Y.Meng,D.L.Herald,K.A.N.Graham,R.K.Pettit and D.L.Doubek,J.Nat.Prod.,2003,66,1065-1069.
(3)K.Cheng,N.J.Rahier,B.M.Eisenhauer,R.Gao,S.J.Thomas and S.M.Hecht,J.Am.Chem.Soc.,2005,127,838-839.
(4)K.B.Simonsen,J.Kehler,K.Juhl,N.Khanzhin and S.M.Nielsen,Patent WO2008131779 A1,2008.
(5)Y.H.Wong,M.K.C.Ho,Y.Q.Hu,D.C.New,X.X.He and H.H.Pang,PatentWO2008092292 A1,2008.
(6)O.Plettenburg,K.Lorenz,J.Goerlitzer and M.Loehn,Patent WO2008077555 A2.
(7)N.Kaila,B.Follows,L.Leung,J.Thomason,A.Huang,A.Moretto,K.Janz,M.Lowe,T.S.Mansour,C.Hubeau,K.Page,P.Morgan,S.Fish,X.Xu,C.Williams and E.Saiah,J.Med.Chem.,2014,57,1299-1322.
(8)L.J.Martin,M.Koegl,G.Bader,X.-L.Cockcroft,O.Fedorov,D.Fiegen,T.Gerstberger,M.H.Hofmann,A.F.Hohmann,D.Kessler,S.Knapp,P.Knesl,S.Kornigg,S.Müller,H.Nar,C.Rogers,K.Rumpel,O.Schaaf,S.Steurer,C.Tallant,C.R.Vakoc,M.Zeeb,A.Zoephel,M.Pearson,G.Boehmelt and D.McConnell,J.Med.Chem.,2016,59,4462-4475.
(9)K.R.Fales,F.G.Njoroge,H.B.Brooks,S.Thibodeaux,A.Torrado,C.Si,J.L.Toth,J.R.Mc Cowan,K.D.Roth,K.J.Thrasher,K.Frimpong,M.R.Lee,R.D.Dally,T.A.Shepherd,T.B.Durham,B.J.Margolis,Z.Wu,Y.Wang,S.Atwell,J.Wang,Y.-H.Hui,T.I.Meier,S.A.Konicek and S.Geeganage,J.Med.Chem.,2017,60,9599-9616.
(10)J.Roth,F.Madoux,P.Hodder and W.R.Roush,Bioorg.Med.Chem.Lett.,2008,18,2628-2632.
(11)P.T.Sunderland,E.C.Y.Woon,A.Dhami,A.B.Bergin,M.F.Mahon,P.J.Wood,L.A.Jones,S.R.Tully,M.D.Lloyd,A.S.Thompson,H.Javaid,N.M.B.Martin and M.D.Threadgill,J.Med.Chem.,2011,54,2049-2059.
(12)C.González-Bello,C.Abell and F.J.Leeper,J.Chem.Soc.,Perkin Trans.1,1997,1,1017-1024.
(13)J.J.Youte,D.Barbier,A.Al-Mourabit,D.Gnecco and C.Marazano,J.Org.Chem.,2004,69,2737-2740.
(14)T.-T.Fan-Chiang,H.-K.Wang and J.-C.Hsieh,Tetrahedron,2016,72,5640-5645.
(15)D.Wang,R.Zhang,R.Deng,S.Lin,S.Guo and Z.Yan,J.Org.Chem.,2016,81,11162-11167.
(16)W.-K.Luo,X.Shi,W.Zhou and L.Yang,Org.Lett.,2016,18,2036-2039.
(17)D.Zhu,W.K.Luo,L.Yang and D.-Y.Ma,Org.Biomol.Chem.,2017,15,7112-7116.
(18)A.Motaleb,A.Bera and P.Maity,Org.Biomol.Chem.,2018,16,5081-5085.
(19)Y.Jin,L.Ou,H.Yang and H.Fu,J.Am.Chem.Soc.,2017,139,14237-14243.
(20)G.Wang,W.Hu,Z.Hu,Y.Zhang,W.Yao,L.Li,Z.Fu and W.Huang,Green Chem.,2018,20,3302-3307.
(21)Z.Fang,Y.Wang and Y.Wang,Org.Lett.,2019,21,434-438.
(22)M.Yan,Y.Kawamata and P.S.Baran,Chem.Rev.,2017,117,13230-13319.
(23)R.Francke and R.D.Little,Chem.Soc.Rev.,2014,43,2492-2521.
(24)Y.Yuan and A.Lei,Nature Commun.,2020,11.
(25)Y.Yuan and A.Lei,Acc.Chem.Res.,2019,52,12,3309-3324.
(26)J.C.Siu,N.Fu and S.Lin,Acc.Chem.Res.,2020,53,547-560.
(27)J.Yoshida,K.Kataoka,R.Horcajada and A.Nagaki,Chem.Rev.2008,108,2265-2299.(28)S.R.Waldvogel and B.Janza,Angew.Chem.Int.Ed.,2014,53,7122-7123.(29)M.K.
Chem.Soc.Rev.2018,47,5786-5865.
(30)L.Sancineto,A.Mariotti,L.Bagnoli,F.Marini,J.Desantis,N.Iraci,C.Santi,C.Pannecouque and O.Tabarrini,J.Med.Chem.,2015,58,9601–9614.
(31)G.Mugesh,W.W.du Mont and H.Sies,Chem.Rev.,2001,101,2125–2180.
(32)C.W.Nogueira,G.Zeni and J.B.T.Rocha,Chem.Rev.,2004,104,6255–6285.
(33)D.S.Rampon,F.S.Rodembusch,J.M.F.M.Schneider,I.H.Bechtold,P.F.B.Goncalves,A.Merlo and P.H.Schneider,J.Mater.Chem.,2010,20,715–722.
(34)I.Samb,J.Bell,P.Y.Toullec,V.Michelet and I.Leray,Org.Lett.,2011,13,1182–1185.
(35)D.Tanini,B.Lupori,G.Malevolti,M.Ambrosi,P.L.Nostro and A.Capperucci,Chem.Commun.,2019,55,5705–5708.
(36)A.Angeli,D.Tanini,A.Nocentini,A.Capperucci,M.Ferraroni,P.Gratteri and C.T.Supuran,Chem.Commun.,2019,55,648–651.
(37)Z.Y.Wen,J.W.Xu,Z.W.Wang,H.Qi,Q.L.Xu,Z.S.Bai,Q.Zhang,K.Bao,Y.L.Wu and W.G.Zhang,Eur.J.Med.Chem.,2015,90,184.
(38)Guan,C.M.Han,D.Y.Zuo,M.A.Zhai,Z.Q.Li,Q.Zhang,Y.P.Zhai,X.W.Jiang,K.Bao,Y.L.Wu and W.G.Zhang,Eur.J.Med.Chem.,2014,87,306–315.
(39)H.R.P.Naik,H.S.B.Naik,T.R.R.Naik,H.R.Naika,K.Gouthamchandra,R.Mahmood,B.M.K.Ahamed Eur.J.Med.Chem.,2009,44,981-989.
(40)H.R.P.Naik,H.S.B.Naik,T.R.R.Naik,H.R.Naika,K.Gouthamchandra,R.Mahmood and B.M.Ahamed,Eur.J.Med.Chem.,2009,44,981-989.
(41)Y.Q.Zhu,J.L.He,Y.X.Niu,el,J.Org.Chem.2018,83,17,9958–9967.
Disclosure of Invention
In view of the problems and defects in the related art, an object of the present invention is to provide a selenoisonone compound and its application in sunscreen cream, which provides a direction for the expansion and application of the selenoisonone compound.
The invention also aims to provide a simple and clean preparation method of the selenized isoquinolone, which accords with the green chemical concept and solves the problems of complex operation and serious pollution in the related technology.
In order to achieve the above objects, one aspect of the present invention provides a selenoisonone compound represented by formula I,
wherein R is1-R6Each independently satisfies the following condition:
R1selected from H, C1-C6Alkyl radical, C2-C6Alkenyl radical, C3-C6Alkynyl or-Ar, wherein said C1-C6Alkyl is optionally substituted with 1,2 or 3 groups independently selected from C1-C6Alkoxy, halogen, -OH, -heterocycloalkyl, C3-C7Cycloalkyl, -C1-C6Alkyl-amino, -di-C1-C6Alkyl-amino or-Ar;
R2is selected from C1-C6Alkyl or-Ar, wherein said C1-C6Alkyl is optionally substituted with 1,2 or 3 groups independently selected from: -C1-C6Alkyl, -C1-C6Alkoxy or-Ar;
R3-R6each independently selected from H, C1-C6Alkyl radical, C1-C6Alkoxy, halogen, -Ar or R3-R6Wherein adjacent two may also form a five-seven membered ring; the five-seven membered ring is selected from saturated aliphatic ring, saturated aliphatic heterocyclic ring, aromatic ring or aromatic heterocyclic ring; the number of heteroatoms in the saturated aliphatic heterocycle or the aromatic heterocycle is 1-2; the five-seven membered ring may be substituted with 1-3 independent substituents selected from-C1-C6Alkyl, -C1-C6Alkoxy, -heterocycloalkyl, -CN, -OH, halogen, -C3-C7Cycloalkyl or-Ar;
-Ar is an aryl or heteroaryl ring, optionally substituted with 1,2 or 3 groups independently selected from: -C1-C6Alkyl, -CN, -OH, -phenyl, -heterocycloalkyl, -C3-C7Cycloalkyl, -C1-C6Alkyl-amino or-di-C1-C6An alkyl-amino group;
C1-C6the alkyl is straight-chain alkyl or branched-chain alkyl with 3-6 carbon atoms.
Further, in the compounds of formula I, R1When it is methyl, R3-R6The following conditions are also satisfied:
R3-R6not H at the same time;
R3-R6in when R is3Is C1When alkyl, R4-R6Not H at the same time; when R is4Is Br or ClWhen R is3And R5-R6Not H at the same time; when R is5Is ClWhen alkyl, R3-R4And R6Is not simultaneousIs H.
Further, in the compounds of formula I, R1-R6Each independently satisfies the following condition:
R1is methyl or ethyl;
R2is phenyl or p-methylphenyl;
R3-R6at least one selected from the group consisting of H, methyl, Cl, Br, methoxy, phenyl and thiophen-2-yl;
when R is1When it is methyl, R3-R6The following conditions are also satisfied:
R3-R6not H at the same time;
R3-R6in when R is3When it is methyl, R4-R6Not H at the same time; when R is4When Br or Cl, R3And R5-R6Not H at the same time; when R is5Is ClWhen R is3-R4And R6Not H at the same time.
In another aspect, the present invention provides a preparation method of a selenized isoquinolone compound, wherein the reaction formula of the preparation method is as follows:
the preparation method comprises the following steps:
mixing N-alkyl isoquinoline salt shown in a formula II and a diselenide ether substrate shown in a formula III, then adding an additive and an electrolyte, adding a solvent to dissolve the mixture, inserting an electrode, and electrifying under a sufficient oxygen environment to carry out electrochemical synthesis.
Further, in the preparation method,
X-is Cl-、Br-、I-Any one of (a);
R1-R6each independently satisfies the following condition:
R1selected from H, C1-C6Alkyl radical, C2-C6Alkenyl radical、C3-C6Alkynyl or-Ar, wherein said C1-C6Alkyl is optionally substituted with 1,2 or 3 groups independently selected from C1-C6Alkoxy, halogen, -OH, -heterocycloalkyl, C3-C7Cycloalkyl, -C1-C6Alkyl-amino, -di-C1-C6Alkyl-amino or-Ar;
R2is selected from C1-C6Alkyl or-Ar, wherein said C1-C6Alkyl is optionally substituted with 1,2 or 3 groups independently selected from: -C1-C6Alkyl, -C1-C6Alkoxy or-Ar;
R3-R6each independently selected from H, C1-C6Alkyl radical, C1-C6Alkoxy, halogen, -Ar or R3-R6Wherein adjacent two may also form a five-seven membered ring; the five-seven membered ring is selected from saturated aliphatic ring, saturated aliphatic heterocyclic ring, aromatic ring or aromatic heterocyclic ring; the number of heteroatoms in the saturated aliphatic heterocycle or the aromatic heterocycle is 1-2; the five-seven membered ring may be substituted with 1-3 independent substituents selected from-C1-C6Alkyl, -C1-C6Alkoxy, -heterocycloalkyl, -CN, -OH, halogen, -C3-C7Cycloalkyl or-Ar;
-Ar is an aryl or heteroaryl ring, optionally substituted with 1,2 or 3 groups independently selected from: -C1-C6Alkyl, -CN, -OH, -phenyl, -heterocycloalkyl, -C3-C7Cycloalkyl, -C1-C6Alkyl-amino or-di-C1-C6An alkyl-amino group;
C1-C6the alkyl is straight-chain alkyl or branched-chain alkyl with 3-6 carbon atoms.
Further, said X-Is I-；
R1-R6Each independently satisfies the following condition:
R1is methyl or ethyl;
R2is phenyl or p-methylphenyl;
R3-R6at least one selected from the group consisting of H, methyl, Cl, Br, methoxy, phenyl and thiophen-2-yl.
Further, in the preparation method, the molar ratio of the compound II to the compound III is 1: 0.5-2.
Further, the molar ratio of the compound II to the compound III is 1: 1.
further, the additive is selected from Cs2CO3、Na2CO3、KH2PO4And K2CO3Any one of the above.
Further, the additive is Cs2CO3。
Further, in the preparation method, the molar ratio of the additive to the compound II is 0.5-2: 1.
Further, the molar ratio of the additive to the compound II is 1.5:1
Further, the electrolyte is selected from KI, KBr, NH4I，n-Bu4NI，n-Bu4NBF4And Et4NPF6Any one of the above.
Further, the electrolyte is KI.
Further, in the preparation method, the molar ratio of the electrolyte to the compound II is 1-5: 1.
Further, in the preparation method, the molar ratio of the electrolyte to the compound II is 5: 1.
Further, in the electrodes, the positive electrode is a graphite electrode (C) or a Pt electrode; the negative electrode is a Pt electrode or a graphite electrode (C).
Further, in the electrode, the positive electrode is a graphite electrode (C).
Further, among the electrodes, the negative electrode is a Pt electrode.
Further, in the preparation method, the electrifying current is constant current.
Further, the constant current is 8-12 mA.
Further, the constant current was 10 mA.
Further, the solvent is selected from CH3CN, THF and water.
Further, the solvent is CH3CN/H2O。
Further, the CH3CN/H2O(V/V)＝X/X。
Further, the CH3CN/H2O(V/V)＝4/1。
Further, the oxygen pressure is 2-3 psi.
Further, the reaction temperature is 20-30 ℃.
Further, the preparation method comprises the following steps: mixing the N-alkylisoquinolinium salt of formula II (1eq) with the diselenide of formula III (1eq), and adding the additive Cs2CO3(1.5eq) and electrolyte KI (5eq), adding solvent CH3CN/H2The mixture was dissolved in O (V/V) ═ 4/1, and a C (+) | Pt (-) electrode was inserted to replace the gas in the reaction flask with O at a pressure of 2-3psi2Electrochemical synthesis was carried out at 25 ℃ with a constant current of 10 mA.
In a further aspect the invention provides the use of a compound of formula I in a sunscreen product.
The main advantages of the invention are:
1. the selenoisonone compound provided by the invention has sun-screening performance.
2. According to the preparation method, N-alkyl isoquinoline salt is used as a raw material, and C (O) -C and C4-C-Se bonds are directly constructed at C1 site in one step at the same time to obtain the selenoisonone compound.
3. The preparation method disclosed by the invention uses an electrochemical synthesis method, avoids the use of a strong oxidant and a toxic oxidant, is simple and clean, and accords with a green chemical concept.
Drawings
Figure 1 ultraviolet absorption spectrum of compound 1;
fig. 2 ultraviolet absorption spectra of selenized isoquinolone sunscreen cream and blank cream.
Detailed Description
The invention will be further described with reference to specific examples, but the scope of the invention is not limited thereto.
Example 1:
81.3mg (0.3mmol) of the N-alkylisoquinolinium salt shown below, 93.6mg (0.3mmol) of the selenoether substrate are introduced into a 20ml reaction flask with stirrer, followed by 146.6mg (0.45mmol) of additive Cs2CO3And 249mg (1.5mmol) of KI, followed by addition of CH3CN/H2O (V/V-4/1) cosolvent was dissolved, and then a C (+) | Pt (-) electrode was inserted to replace the gas in the reaction flask with O at a pressure of 2-3psi2The reaction was carried out at 25 ℃ under 10mA current for 10 hours, and the target product was isolated by silica gel chromatography after spin-drying in 83% yield.
1H NMR(400MHz,CDCl3)δppm 8.46(d,J＝8.9Hz,1H),7.93(d,J＝7.8Hz,1H),7.71(s,1H),7.63(t,J＝8.4Hz,1H),7.51(t,J＝8.1Hz,1H),7.24(d,J＝1.5Hz,2H),7.21–7.14(m,3H),3.64(s,3H).
13C NMR(100MHz,CDCl3)δppm 162.6,140.9,137.9,132.8,132.3,129.3,129.0,128.1,127.5,127.3,126.4,104.1,37.0.
HR-MALDI-MS m/z calcd.for C16H13NOSe[M+H]+:316.0241,found:316.0240.
Example 2:
81.3mg (0.3mmol) of the N-alkylisoquinolinium salt shown below, 93.6mg (0.3mmol) of the selenoether substrate are introduced into a 20ml reaction flask with stirrer, followed by 62.2mg (0.45mmol) of additive K2CO3And 249mg (1.5mmol) of KI, followed by addition of CH3CN/H2O (V/V-2/1) cosolvent was dissolved, and then a C (+) | Pt (-) electrode was inserted to replace the gas in the reaction flask with O at a pressure of 2-3psi2The reaction was carried out at 25 ℃ under 10mA current for 10 hours, and the target product was isolated by silica gel chromatography after spin-drying in 63% yield.
1H NMR(400MHz,CDCl3)δppm 8.46(d,J＝8.9Hz,1H),7.93(d,J＝7.8Hz,1H),7.71(s,1H),7.63(t,J＝8.4Hz,1H),7.51(t,J＝8.1Hz,1H),7.24(d,J＝1.5Hz,2H),7.21–7.14(m,3H),3.64(s,3H).
13C NMR(100MHz,CDCl3)δppm 162.6,140.9,137.9,132.8,132.3,129.3,129.0,128.1,127.5,127.3,126.4,104.1,37.0.
HR-MALDI-MS m/z calcd.for C16H13NOSe[M+H]+:316.0241,found:316.0240.
Example 3:
81.3mg (0.3mmol) of the N-alkylisoquinolinium salt shown below, 93.6mg (0.3mmol) of the selenoether substrate are introduced into a 20ml reaction flask with stirrer, followed by 146.6mg (0.45mmol) of additive Cs2CO3And 554.1mg (1.5mmol) of n-Bu4NI, then CH is added3CN/H2O (V/V-4/1) cosolvent was dissolved, and then a C (+) | Pt (-) electrode was inserted to replace the gas in the reaction flask with O at a pressure of 2-3psi2The reaction was carried out at 25 ℃ under 10mA current for 10 hours, and the target product was isolated by silica gel chromatography after spin-drying in 45% yield.
1H NMR(400MHz,CDCl3)δppm 8.46(d,J＝8.9Hz,1H),7.93(d,J＝7.8Hz,1H),7.71(s,1H),7.63(t,J＝8.4Hz,1H),7.51(t,J＝8.1Hz,1H),7.24(d,J＝1.5Hz,2H),7.21–7.14(m,3H),3.64(s,3H).
13C NMR(100MHz,CDCl3)δppm 162.6,140.9,137.9,132.8,132.3,129.3,129.0,128.1,127.5,127.3,126.4,104.1,37.0.
HR-MALDI-MS m/z calcd.for C16H13NOSe[M+H]+:316.0241,found:316.0240.
Example 4:
81.3mg (0.3mmol) of the N-alkylisoquinolinium salt shown below, 93.6mg (0.3mmol) of the selenoether substrate are introduced into a 20ml reaction flask with stirrer, followed by 146.6mg (0.45mmol) of additive Cs2CO3And 249mg (1.5mmol) of KI, followed by addition of CH3CN/H2O (V/V-4/1) cosolvent was dissolved, and then a C (+) | Pt (-) electrode was inserted to replace the gas in the reaction flask with O at a pressure of 2-3psi2The reaction was carried out at 25 ℃ under 8mA current for 10 hours, and the target product was isolated by silica gel chromatography after spin-drying in 80% yield.
1H NMR(400MHz,CDCl3)δppm 8.46(d,J＝8.9Hz,1H),7.93(d,J＝7.8Hz,1H),7.71(s,1H),7.63(t,J＝8.4Hz,1H),7.51(t,J＝8.1Hz,1H),7.24(d,J＝1.5Hz,2H),7.21–7.14(m,3H),3.64(s,3H).
13C NMR(100MHz,CDCl3)δppm 162.6,140.9,137.9,132.8,132.3,129.3,129.0,128.1,127.5,127.3,126.4,104.1,37.0.
HR-MALDI-MS m/z calcd.for C16H13NOSe[M+H]+:316.0241,found:316.0240.
Example 5:
66.9mg (0.3mmol) of the N-alkylisoquinolinium salt shown below, 93.6mg (0.3mmol) of the selenoether substrate are introduced into a 20ml reaction flask with stirrer, followed by 146.6mg (0.45mmol) of additive Cs2CO3And 249mg (1.5mmol) of KI, followed by addition of CH3CN/H2O (V/V-4/1) cosolvent was dissolved, and then a C (+) | Pt (-) electrode was inserted to replace the gas in the reaction flask with O at a pressure of 2-3psi2The reaction was carried out at 25 ℃ under 10mA current for 10 hours, and the target product was isolated by silica gel chromatography after spin-drying in 78% yield.
1H NMR(400MHz,CDCl3)δppm 8.46(d,J＝8.9Hz,1H),7.93(d,J＝7.8Hz,1H),7.71(s,1H),7.63(t,J＝8.4Hz,1H),7.51(t,J＝8.1Hz,1H),7.24(d,J＝1.5Hz,2H),7.21–7.14(m,3H),3.64(s,3H).
13C NMR(100MHz,CDCl3)δppm 162.6,140.9,137.9,132.8,132.3,129.3,129.0,128.1,127.5,127.3,126.4,104.1,37.0.
HR-MALDI-MS m/z calcd.for C16H13NOSe[M+H]+:316.0241,found:316.0240.
Example 6:
85.5mg (0.3mmol) of the N-alkylisoquinolinium salt shown below, 93.6mg (0.3mmol) of the selenoether substrate are introduced into a 20ml reaction flask with stirrer, followed by 146.6mg (0.45mmol) of additive Cs2CO3And 249mg (1.5mmol) of KI, followed by addition of CH3CN/H2O (V/V-4/1) cosolvent was dissolved, and then a C (+) | Pt (-) electrode was inserted to replace the gas in the reaction flask with O at a pressure of 2-3psi2The reaction was carried out at 25 ℃ under 10mA current for 10 hours, and the target product was isolated by silica gel chromatography after spin-drying in 82% yield.
1H NMR(400MHz,CDCl3)δppm 8.35(d,J＝8.2Hz,1H),7.73(s,1H),7.67(s,1H),7.32(d,J＝7.5Hz,1H),7.24(t,J＝1.6Hz,2H),7.21–7.13(m,3H),3.62(s,3H),2.43(s,3H).
13C NMR(100MHz,CDCl3)δppm 162.6,143.5,141.1,138.0,132.5,129.3,129.0,128.9,128.1,126.9,126.3,124.1,103.9,36.9,22.0.
HRMS MALDI m/z calcd.for C17H15NOSe[M+H]+:330.0397,found:330.0400.
Example 7:
104.7mg (0.3mmol) of the N-alkylisoquinolinium salt shown below, 93.6mg (0.3mmol) of the selenoether substrate are added to a 20ml reaction flask with stirrer, followed by146.6mg (0.45mmol) of additive Cs are added2CO3And 249mg (1.5mmol) of KI, followed by addition of CH3CN/H2O (V/V-4/1) cosolvent was dissolved, and then a C (+) | Pt (-) electrode was inserted to replace the gas in the reaction flask with O at a pressure of 2-3psi2The reaction was carried out at 25 ℃ under 10mA current for 10 hours, and the target product was isolated by silica gel chromatography after spin-drying in 77% yield.
1H NMR(400MHz,CDCl3)δppm 8.29(d,J＝8.6Hz,1H),8.12(d,J＝1.9Hz,1H),7.71(s,1H),7.60–7.57(m,1H),7.26–7.16(m,5H),3.62(s,3H).
13C NMR(100MHz,CDCl3)δppm 162.1,142.2,139.6,131.8,130.8,129.9,129.9,129.4,129.3,128.4,126.7,125.0,103.1,37.1.
HRMS MALDI m/z calcd.for C16H12BrNOSe[M+H]+:393.9346,found:393.9348.
Example 8:
90.3mg (0.3mmol) of the N-alkylisoquinolinium salt shown below, 93.6mg (0.3mmol) of the selenoether substrate are introduced into a 20ml reaction flask with stirrer, followed by 146.6mg (0.45mmol) of additive Cs2CO3And 249mg (1.5mmol) of KI, followed by addition of CH3CN/H2O (V/V-4/1) cosolvent was dissolved, and then a C (+) | Pt (-) electrode was inserted to replace the gas in the reaction flask with O at a pressure of 2-3psi2The reaction was carried out at 25 ℃ under 10mA current for 10 hours, and the target product was isolated by silica gel chromatography after spin-drying in 72% yield.
1H NMR(400MHz,CDCl3)δppm 7.86–7.82(m,2H),7.57(s,1H),7.23–7.13(m,6H),3.91(s,3H),3.63(s,3H).
13C NMR(100MHz,CDCl3)δppm 162.3,159.2,138.5,132.4,131.8,129.3,129.0,129.0,127.5,126.3,123.0,108.0,104.0,55.7,37.1.
HRMS MALDI m/z calcd.for C17H15NO2Se[M+H]+:346.0346,found:346.0355.
Example 9:
105.9mg (0.3mmol) of the N-alkylisoquinolinium salt shown below, 93.6mg (0.3mmol) of the selenoether substrate are introduced into a 20ml reaction flask with stirrer, followed by 146.6mg (0.45mmol) of additive Cs2CO3And 249mg (1.5mmol) of KI, followed by addition of CH3CN/H2O (V/V-4/1) cosolvent was dissolved, and then a C (+) | Pt (-) electrode was inserted to replace the gas in the reaction flask with O at a pressure of 2-3psi2The reaction was carried out at 25 ℃ under 10mA current for 10 hours, and the target product was isolated by silica gel chromatography after spin-drying in 64% yield.
1H NMR(400MHz,CDCl3)δppm 8.41(d,J＝9.0Hz,1H),8.12(s,1H),7.70(d,J＝9.0Hz,2H),7.36–7.31(m,4H),7.21–7.13(m,3H),7.06(t,J＝3.7Hz,1H),3.61(s,3H).
13C NMR(100MHz,CDCl3)δppm 162.3,143.1,141.3,138.4,132.0,129.7,129.4,128.9,128.3,126.7,126.6,125.1,125.0,124.8,123.8,104.4,37.0.
HRMS MALDI m/z calcd.for C20H15NOSSe[M+H]+:398.0118,found:398.0119.
Example 10:
104.1mg (0.3mmol) of the N-alkylisoquinolinium salt shown below, 93.6mg (0.3mmol) of the selenoether substrate are introduced into a 20ml reaction flask with stirrer, followed by 146.6mg (0.45mmol) of additive Cs2CO3And 249mg (1.5mmol) of KI, followed by addition of CH3CN/H2O (V/V-4/1) cosolvent was dissolved, and then a C (+) | Pt (-) electrode was inserted to replace the gas in the reaction flask with O at a pressure of 2-3psi2Reacting at 25 ℃ under 10mA currentAfter 10 hours of spin-drying, the desired product was isolated by silica gel chromatography in 75% yield.
1H NMR(400MHz,CDCl3)δppm 8.70(s,1H),7.97(d,J＝8.4Hz,1H),7.85(d,J＝8.1Hz,1H),7.71–7.66(m,3H),7.45(t,J＝7.6Hz,2H),7.36(t,J＝7.3Hz,1H),7.27(d,J＝7.5Hz,2H),7.16(dd,J＝9.4,6.9Hz,3H),3.64(s,3H).
13C NMR(100MHz,CDCl3)δppm 162.7,140.8,140.2,139.7,136.9,132.3,131.7,129.4,129.1,129.0,128.0,127.9,127.2,126.7,126.4,126.0,103.9,37.1.
HRMS MALDI m/z calcd.for C22H17NOSe[M+H]+:392.0554,found:392.0554.
Example 11:
85.5mg (0.3mmol) of the N-alkylisoquinolinium salt shown below, 93.6mg (0.3mmol) of the selenoether substrate are introduced into a 20ml reaction flask with stirrer, followed by 146.6mg (0.45mmol) of additive Cs2CO3And 249mg (1.5mmol) of KI, followed by addition of CH3CN/H2O (V/V-4/1) cosolvent was dissolved, and then a C (+) | Pt (-) electrode was inserted to replace the gas in the reaction flask with O at a pressure of 2-3psi2The reaction was carried out at 25 ℃ under 10mA current for 10 hours, and the target product was isolated by silica gel chromatography after spin-drying in 79% yield.
1H NMR(400MHz,CDCl3)δppm 8.46(d,J＝7.8Hz,1H),7.92(d,J＝8.2Hz,1H),7.70(s,1H),7.62(t,J＝7.9Hz,1H),7.53–7.47(m,1H),7.24(d,J＝1.6Hz,2H),7.17(q,J＝7.8,7.0Hz,3H),4.10(q,J＝7.2Hz,2H),1.42(t,J＝7.2Hz,3H).
13C NMR(100MHz,CDCl3)δppm 162.0,139.8,137.7,132.8,132.3,129.3,129.0,128.2,127.4,127.2,126.6,126.3,104.3,44.5,14.7.
HRMS MALDI(m/z):calcd for C17H15NOSe[M+H]+:330.0397,found:330.0398.
Example 12:
81.0mg (0.3mmol) of the N-alkylisoquinolinium salt shown below, 102.6mg (0.3mmol) of the selenoether substrate are introduced into a 20ml reaction flask with stirrer, followed by 146.6mg (0.45mmol) of additive Cs2CO3And 249mg (1.5mmol) of KI, followed by addition of CH3CN/H2O (V/V-4/1) cosolvent was dissolved, and then a C (+) | Pt (-) electrode was inserted to replace the gas in the reaction flask with O at a pressure of 2-3psi2The reaction was carried out at 25 ℃ under 10mA current for 10 hours, and the target product was isolated by silica gel chromatography after spin-drying in 70% yield.
1H NMR(400MHz,CDCl3)δppm 8.45(d,J＝9.4Hz,1H),7.94(d,J＝7.6Hz,1H),7.68(s,1H),7.63(t,J＝8.4Hz,1H),7.49(t,J＝7.0Hz,1H),7.18(d,J＝8.2Hz,2H),7.00(d,J＝7.9Hz,2H),3.63(s,3H),2.26(s,3H).
13C NMR(100MHz,CDCl3)162.6,140.6,137.9,136.5,132.8,130.1,129.5,128.2,128.0,127.4,127.3,126.4,104.7,37.0,21.0.
HRMS MALDI(m/z):calcd for C17H15NOSe[M+H]+:330.0397,found:330.0406.
Through the above examples, those skilled in the art can understand that the compound of formula II mentioned in the summary of the present invention can obtain the selenized isoquinolone compound represented by formula I through the preparation method provided by the present invention.
Effect example 1
Ultraviolet light absorption Performance test
In the UVB region, evaluation was carried out by ultraviolet spectroscopy.
Weighing 10.0391 g of the following selenized isoquinolone compound, adding 1mL of dimethyl sulfoxide into an EP tube for dissolving, and transferringPut into a 100mL volumetric flask, continuously diluted to the scale with dimethyl sulfoxide, and shaken up for standby. Taking 1mL of the solution, transferring the solution into a 100mL volumetric flask, diluting to a scale, and uniformly mixing to 10%-5mol·L-1Standard stock solutions, detected by uv absorption.
The absorption strength of the compounds in different solvents was determined, DMSO was replaced with another solvent, and the above experimental procedure was repeated. And testing the absorbance of the selenoisonone compound under different solvents, and evaluating the protective effect of the UVB region.
The chemical structural formulas of the selenoisonone compounds 1-5 are as follows:
the test results of the selenoisonone compound 1 in the UVB region are shown in fig. 1. In addition, ultraviolet absorption tests are carried out on the selenoisonone compounds 2-5, and the results show that the selenoisonone compounds have a strong absorption effect in various solvents within the range of 290-350 nm and have a certain protection effect in a UVB region.
Effect example 2
Ultraviolet absorption Performance test of sunscreen cream
The formula of the selenized isoquinolone sunscreen cream is as follows:
sunscreen base formula table
Blank cream: the difference with the selenized isoquinolone sunscreen cream is that the base formula of the sunscreen cream does not contain the compound 1.
The preparation method of the sunscreen cream and the blank cream comprises the following steps:
taking a beaker (recording the weight of the beaker, recording as A cup), accurately weighing each raw material of the phase A, heating to 80 ℃ and stirring. Accurately weighing each raw material of phase B in another beaker (marked as cup B), heating to 80 deg.C, and stirring. Adding the raw materials of B cup into A cup, and homogenizing for 3 min. Cooling to 50 deg.C, and adding C phase material. Stirring and cooling to about 45 ℃, adding the D-phase raw material, and uniformly stirring to obtain the composition.
Accurately weighing 1g of hollow white cream and each 1g of the selenized isoquinolone sunscreen cream, adding absolute ethyl alcohol to dissolve the hollow white cream and the selenized isoquinolone sunscreen cream, metering the volume to 100ml, and measuring the absorbance within the wavelength range of 280 plus 400 nm.
The test result is shown in fig. 2, and it can be seen that, due to the addition of the isoquinolone selenide compound, compared with the blank cream, the ultraviolet absorption performance of the prepared sunscreen cream in the wavelength ranges of UVB (280-320nm) and UVA (320-400nm) is obviously improved, which indicates that the prepared isoquinolone selenide sunscreen cream has better ultraviolet absorption performance. In addition, ultraviolet absorption tests are also carried out on the sunscreen cream prepared from the selenized isoquinolone compounds 2-5 by the same method, and the results show that the ultraviolet absorption performance of the sunscreen cream prepared from the selenized isoquinolone compounds 2-5 in the wavelength range of 320-400nm is obviously improved, which shows that the selenized isoquinolone sunscreen cream provided by the invention has better ultraviolet absorption performance.
Effect example 3
Chick embryo chorioallantoic membrane blood vessel test
Drilling a small hole at the top of an air chamber of a 9-12-day-old chick embryo, slightly clamping an eggshell by using a pair of tweezers to expose an eggshell membrane, blowing away eggshell fragments by using an ear washing ball, dripping 3-4 drops of normal saline on the eggshell membrane, pouring the redundant normal saline, and uncovering the eggshell membrane by using sterile tweezers to find out the chorioallantoic membrane of the chick embryo.
Negative control group: 0.3mL of 0.9% sodium chloride solution was applied to the chick embryo chorioallantoic membrane for 5min as a negative control.
Positive control group: 0.1mol/L NaOH solution is taken to act on chick embryo chorioallantoic membrane for 5min as positive control.
Experimental groups: dripping 0.3mL of the solution to be detected on the surface of the chick chorioallantoic membrane, observing the blood vessel change and the initial time of bleeding, hemolysis and coagulation in 5min of the chick chorioallantoic membrane, calculating the stimulation score (IS) according to the result by the formula (7), and keeping the two digits after the decimal point.
In the formula: sec H is the mean time to first bleeding(s) of the CAM; sec L is the mean time to vascular melting of the CAM,(s); sec C (clotting time) is the average time to onset of clotting in the CAM,(s).
The evaluation criteria of the chick embryo chorioallantoic membrane blood vessel test are as follows:
the experiment is carried out by using selenoisonone 1 with the concentration of 10mg/mL as an experimental group test solution. The results show that secH, secL and secC of the selenized isoquinolone 1 of 10mg/mL are all 300s, the calculated IS value IS 0.07, less than 1, and no irritation exists. In addition, the same method IS adopted to carry out chick embryo chorioallantoic membrane blood vessel tests on the selenoisonone compounds 2-5, IS IS less than 1, and the results show that no irritation exists in the compounds 2-5.
As can be seen from the effect examples 1-3, the selenoisonone compound provided by the invention has a strong absorption effect in the wavelength range of 290-350 nm, and has a certain protection effect in a UVB region. After the invention is applied to the sunscreen cream, the ultraviolet absorption performance of the sunscreen cream prepared by using the selenizing isoquinolone compound is obviously improved in the wavelength ranges of UVB (280-320nm) and UVA (320-400nm), and the selenizing isoquinolone sunscreen cream prepared by using the selenizing isoquinolone compound is shown to have better ultraviolet absorption performance. Meanwhile, the selenoisonone compound provided by the invention has no irritation in a chick embryo chorioallantoic membrane blood vessel test, so that the selenoisonone compound provided by the invention can be used in the production of sunscreen products.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that are within the spirit and principle of the present invention are intended to be included in the scope of the present invention.
Claims (8)
1. Selenoisonone compound represented by formula I
Wherein R is1-R6Each independently satisfies the following condition:
R1is methyl or ethyl;
R2is phenyl or p-methylphenyl;
R3-R6at least one selected from the group consisting of H, methyl, Cl, Br, methoxy, phenyl and thiophen-2-yl.
2. The compound of claim 1,
when R is1When it is methyl, R3-R6The following conditions are also satisfied:
R3-R6not H at the same time.
3. A preparation method of a selenoisonone compound, which has the following reaction formula:
the preparation method comprises the following steps:
mixing N-alkyl isoquinoline salt shown in a formula II with a diselenide substrate shown in a formula III, then adding an additive and an electrolyte, adding a solvent to dissolve the mixture, inserting an electrode, and electrifying to carry out electrochemical synthesis in a sufficient oxygen environment;
the additive is selected from Cs2CO3、Na2CO3、KH2PO4And K2CO3Any one of (a);
the electrolyte is selected from KI, KBr, NH4I，n-Bu4NI，n-Bu4NBF4And Et4NPF6Any one of (a);
the oxygen pressure is 2-3 psi;
wherein, X-Is Cl-、Br-、I-Any one of (a);
R1-R6each independently satisfies the following condition:
R1is methyl or ethyl;
R2is phenyl or p-methylphenyl;
R3-R6at least one selected from the group consisting of H, methyl, Cl, Br, methoxy, phenyl and thiophen-2-yl.
4. The method according to claim 3, wherein the molar ratio of compound II to compound III in the method is 1: 0.5-2; the molar ratio of the additive to the compound II is 0.5-2: 1; the molar ratio of the electrolyte to the compound II is 1-5: 1; in the electrodes, the positive electrode is a graphite electrode or a Pt electrode; the negative electrode is a Pt electrode or a graphite electrode; the solvent is selected from CH3CN, THF and water.
5. The method according to claim 4, wherein the molar ratio of compound II to compound III in the preparation method is 1: 1; the additive is Cs2CO3The molar ratio of the compound II to the compound II is 1.5: 1; the electrolyte is KI, and the molar ratio of the KI to the compound II is 5: 1; in the electrodes, the positive electrode is a graphite electrode, and the negative electrode is a Pt electrode; the solvent is CH3CN/H2O mixed solvent; the electrified current is a constant current of 8-12 mA; the reaction temperature is 20-30 ℃.
6. The method according to claim 5, wherein the solvent is CH3CN/H2O-4/1; the current was 10 mA.
7. The production method according to claim 3,
X-is I-；
R1-R6Each independently satisfies the followingConditions are as follows:
R1is methyl or ethyl;
R2is phenyl or p-methylphenyl;
R3-R6at least one selected from the group consisting of H, methyl, Cl, Br, methoxy, phenyl and thiophen-2-yl.
8. The application of the selenized isoquinolone compound is characterized in that the selenized isoquinolone compound is applied to a sunscreen product; wherein the selenoisonone compound is a compound represented by formula I,
wherein R is1-R6Each independently satisfies the following condition:
R1is methyl or ethyl;
R2is phenyl or p-methylphenyl;
R3-R6at least one selected from the group consisting of H, methyl, Cl, Br, methoxy, phenyl and thiophen-2-yl.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010966459.2A CN111925326B (en) | 2020-09-15 | 2020-09-15 | Selenoisonone compound and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010966459.2A CN111925326B (en) | 2020-09-15 | 2020-09-15 | Selenoisonone compound and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111925326A CN111925326A (en) | 2020-11-13 |
| CN111925326B true CN111925326B (en) | 2021-11-23 |
Family
ID=73335323
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010966459.2A Active CN111925326B (en) | 2020-09-15 | 2020-09-15 | Selenoisonone compound and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111925326B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117247352A (en) * | 2023-09-15 | 2023-12-19 | 上海陶术生物科技有限公司 | Method for synthesizing selenized isoquinolone derivative based on photocatalysis and application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107108429A (en) * | 2015-12-23 | 2017-08-29 | 联邦科学与工业研究组织 | Compound |
| CN111053775A (en) * | 2009-11-20 | 2020-04-24 | 西姆莱斯股份公司 | Physiologically cooling active ingredients and use of substances containing such active ingredients |
-
2020
- 2020-09-15 CN CN202010966459.2A patent/CN111925326B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111053775A (en) * | 2009-11-20 | 2020-04-24 | 西姆莱斯股份公司 | Physiologically cooling active ingredients and use of substances containing such active ingredients |
| CN107108429A (en) * | 2015-12-23 | 2017-08-29 | 联邦科学与工业研究组织 | Compound |
Non-Patent Citations (3)
| Title |
|---|
| AgSbF6-Mediated Selective Thiolation and Selenylation at C-4 Position of Isoquinolin-1(2H-ones;You-Quan Zhu,等;《J. Org. Chem.》;20180711;9958-9967,table3中化合物3aa、3ab、3ac * |
| Metal-free regioselective direct thiolation of 2-pyridones;Kunita Phakdeeyothin，等;《Org. Biomol. Chem.》;20190614;6432-6440,table3中化合物4m * |
| Regio- and Stereoselective Synthesis of Isoindolin-1-ones via Electrophilic Cyclization;Tuanli Yao，等;《J. Org. Chem.》;20050127;1432-1437,table2中entry4的产物7 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111925326A (en) | 2020-11-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Liu et al. | Visible-light promoted one-pot synthesis of sulfonated spiro [4, 5] trienones from propiolamides, anilines and sulfur dioxide under transition metal-free conditions | |
| Ma et al. | Photocatalytic transition-metal-free direct 3-alkylation of 2-aryl-2 H-indazoles in dimethyl carbonate | |
| Baranov et al. | A synthetic approach to GFP chromophore analogs from 3-azidocinnamates. Role of methyl rotors in chromophore photophysics | |
| CN111925326B (en) | Selenoisonone compound and preparation method and application thereof | |
| Chen et al. | Photocatalyst and additive-free visible light induced trifluoromethylation–arylation of N-arylacrylamides with Umemoto's reagent | |
| CN105164318A (en) | Electrochemical coupling of two phenols which differ in their oxidation potential | |
| Wang et al. | One-pot synthesis of 2-hydroxymethylindoles via photoredox-catalyzed ketyl–ynamide coupling/1, 3-allylic alcohol transposition | |
| Font et al. | Indoles and pyridazino [4, 5-b] indoles as nonnucleoside analog inhibitors of HIV-1 reverse transcriptase | |
| Chen et al. | Efficient synthesis of functionalized pyrido [2, 3-c] coumarin derivatives by a one-pot three-component reaction | |
| Hong et al. | Direct electrochemical reductive amination between aldehydes and amines with a H/D-donor solvent | |
| Teng et al. | Synthesis of benzannulated spiroketals with gold-catalyzed cycloisomerization/spiroketalization cascade | |
| Du et al. | Photochemical and electrochemical C–N borylation of arylhydrazines | |
| Guan et al. | Catalyst-and oxidant-free electrooxidative site-selective [3/4+ 2] annulation to fused polycyclic heteroaromatics | |
| Wenyi et al. | Electrochemical Selenylation of N-Unprotected Anilines for Consturcing 4-(Organylselanyl) anilines | |
| Liu et al. | Cyclometalated iridium (III) complexes containing an anthracene unit for sensing and imaging singlet oxygen in cellular mitochondria | |
| Cen et al. | Electrochemical Selenylation of Alkynyl Aryl Ketones: Efficient Synthesis of 3‐Selenylated Chromones under Catalyst‐and Chemical‐Oxidant‐Free Conditions | |
| Lombardino | Preparation of some 4‐hydroxyl‐1‐methyl‐1H‐2, 1‐benzothiazine‐3‐carboxanilide 2, 2‐dioxides | |
| CN107522584A (en) | A kind of α trifluoromethyl ketones compound and preparation method thereof | |
| Yu et al. | Regioselective electrochemical radical cascade cyclization of internal alkynes to selenated and trifluoromethylated dihydropyran | |
| Yuan et al. | Total synthesis, structural revision and biological evaluation of γ-elemene-type sesquiterpenes | |
| Cui et al. | Stereoselective synthesis of enamino ketones through an aza-Michael/hydrolysis cascade reaction | |
| CN115124531A (en) | 4-azatryptanthrin aromatic thioether derivatives, and preparation method and application thereof | |
| Reddy et al. | A" green" synthesis of N-(quinoline-3-ylmethylene) benzohydrazide derivatives and their cytotoxicity activities | |
| Shimizu et al. | Regioselectivity of 1, 3-dipolar cycloaddition reactions of nitrilimines with aryl vinyl sulfones | |
| Petrini et al. | Oxidative conversion of sulfonyl indoles into 3-alkylidene-2-oxindoles under flow chemical conditions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |