CN106380456B - A method of synthesis benzofuran naphthoquinone derivatives - Google Patents
A method of synthesis benzofuran naphthoquinone derivatives Download PDFInfo
- Publication number
- CN106380456B CN106380456B CN201610756212.1A CN201610756212A CN106380456B CN 106380456 B CN106380456 B CN 106380456B CN 201610756212 A CN201610756212 A CN 201610756212A CN 106380456 B CN106380456 B CN 106380456B
- Authority
- CN
- China
- Prior art keywords
- benzofuran
- raw material
- naphthoquinone derivatives
- solvent
- hydrogen persulfate
- 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.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/92—Naphthofurans; Hydrogenated naphthofurans
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention discloses it is a kind of synthesize benzofuran naphthoquinone derivatives method, with
Description
Technical field
The present invention relates to a kind of methods for synthesizing benzofuran naphthoquinone derivatives, in particular to synthesis 2- acetyl furan naphthalene
The method of quinone derivative and Avicennia marina quinone C.
Background technique
Bronze bell Mu Shu crape myrtle section Lapacho (roble) originates in South America, containing there are many naphthalenes in the bark and core material of Lapacho
Quinones active constituent has significant curative effect in antibacterial, anti-inflammatory, antiviral, anti-trypanosome and anti-tumor aspect.The study found that furan
Naphthaquinone derivatives of muttering are correct and neck, lung, brain, colon, liver cancer, oophoroma, cancer of pancreas and renal carcinoma cell line have stronger suppression
Production is used, and they also show very high activity in anti-leukocythemia and for the lively object of exo-antigen of schizotrypanum cruzi.Its
Not only anti-tumor activity is high for middle natural products 2- acetyl furan naphthoquinones (compound 1), but also has broad spectrum activity, currently, the change
Object is closed to have entered in the test of third stage inhibitor against colon carcinoma cells in America & Canada.
Avicenna marina (lapacho wood) belongs to Acanthaceae, commonly known as mangrove.For bite by mosquitos, skin tinea,
The diseases such as scabies have special effect.In recent years, researcher is from wherein extracting the important activities ingredient such as naphthoquinones and its derivative.It is logical
A large amount of biological experiment discovery is crossed, naphthoquinones and its derivative have antirheumatic, antibacterial, antiproliferative, anti-tumor activity.Wherein day
Right product Avicennia marina quinone C (compound 3) not only has preferable anti-tumor activity, but also can inhibit soliton-typed solution 1
(Molecules 2014,19,6809-6821).Separableization from the plants such as lapacho, Newbouldia leavis
Close object 2, the compound have antitumor, anti-onchocercosis isoreactivity (Med Chem Res (2015) 24:965-969,
J.Nat.Prod.1999,62,1134-1136)。
It is reported that 2- acetyl furan naphthoquinones (compound 1) synthetic method there are many kinds of, such as use CrO3It is right
2- ethyl furan naphthoquinones carries out oxidation reaction；2- (1- ethoxy) naphtho- [2,3-b] furans -4,9- diketone is carried out with PCC
Oxidation reaction；1- (4,9- dimethoxy-4 ', 9- dihydro-naphtho [2,3-b] furans -2- base) ethyl ketone is carried out with DBU or CAN
Oxidation reaction；With MnO22- acetyl group -2,3- dihydro-naphtho [2,3-b] furans -4,9- diketone is aoxidized etc..But this
Methods have the shortcomings that many a bit, as reagent is larger to human toxicity, environment is unfriendly, reaction step number multioperation is complicated, yield
Lowly, the heavy metal etc. for needing toxicity big.Compound 2 is usually obtained by the reduction reaction of compound 1.In particular, not having so far
The efficient synthesis of document report natural products Avicennia marina quinone C (compound 3).
Therefore, the new high-efficiency synthesis method of one kind is developed to prepare benzofuran naphthoquinone derivatives, especially prepares 2- second
Acyl group furans naphthoquinones and Avicennia marina quinone C have practical significance.
Summary of the invention
Present invention solves the technical problem that being to provide a kind of new method for synthesizing benzofuran naphthoquinone derivatives, can keep away
Exempt from existing synthetic method is larger to human toxicity, environment is unfriendly, reaction step number multioperation complexity, low yield, need poison
The problems such as property big heavy metal.
The technical scheme is that a kind of method for synthesizing benzofuran naphthoquinone derivatives is provided, withOxidation reaction is carried out in solvent and is obtained under hydrogen persulfate radical ion and bromide ion effect for raw material
To benzofuran naphthoquinone derivatives；Wherein, having one or two substituent group in R1, R2 and R3 is H atom, remaining substituent group is
The alkyl chain of C1-C6.
Further, the hydrogen persulfate radical ion is provided by potassium hydrogen persulfate；The bromide ion is provided by potassium bromide.
Further, remaining substituent group in R1, R2 and R3 in addition to H is methyl.
Further, the temperature of the oxidation reaction is 0-50 DEG C.
Further, the temperature of the oxidation reaction is 30-50 DEG C.
Further, the solvent is the mixed solvent that water and organic solvent form.
Further, the volume ratio of the organic solvent and water is 12:(1-4)；Further, the solvent and raw material
Mass ratio is (50-400): 1.
Further, the molar ratio of the hydrogen persulfate radical ion and raw material is (2-4): 1；Further, the solvent
Mass ratio with potassium hydrogen persulfate is (50-100): 1.
Further, the molar ratio of the bromide ion and raw material is (0.5-1): 1；Further, the solvent and bromination
The mass ratio of potassium is (800-1000): 1.
Further, the benzofuran naphthoquinone derivatives include:
Potassium hydrogen persulfate (oxone)-potassium bromide (KBr) oxysome is not applied to benzofuran naphthoquinone derivatives before this
In, present invention discover that potassium hydrogen persulfate (oxone)-potassium bromide (KBr) oxidation benzofuran naphthoquinone derivatives raw material effect is non-
Chang Hao.Certainly for such oxidation reaction, the substituent group on furan nucleus is required harsher: withFor
Example, must there is H on substituent group, i.e., R1, R2 and R3 must at least one substituent group be H, and R1, R2 and R3 cannot be H simultaneously,
Otherwise the oxidation effectiveness that cannot be oxidized or be not achieved；Meanwhile the substituent group in addition to H must be alkyl, and alkyl chain
It is shorter, it is the alkyl chain substituent of C1-C6, most representational is methyl.Natural products 2- acetyl furan naphthoquinones and white
The corresponding synthesis material situation of bone earth quinone C is respectively: in R1, R2 and R3 two be H, one be methyl；And two be methyl,
One is hydrogen.
The invention has the advantages that compared with prior art, present invention has an advantage that
1) the present invention provides a kind of potassium hydrogen persulfate (oxone)-potassium bromide (KBr) oxidation systems to synthesize benzofuran naphthalene
The variation route and method of quinone derivative, especially natural products 2- acetyl furan naphthoquinones and Avicennia marina quinone C；
2) synthetic method of the invention is environmental-friendly, and experimental procedure is few, easy to operate, high income, selectivity it is good, have compared with
High application value.
Specific embodiment
Embodiment 1
23mg (0.1mmol) 2- ethyl furan naphthoquinones is dissolved in 6mL acetonitrile and 1mL water, and potassium hydrogen persulfate 139mg is added
(0.22mmol) and potassium bromide 6mg (0.05mmol).After 45 DEG C are reacted 1 day, TLC shows that raw material completely disappears, first in appearance
Mesosome 2 and 4 adds potassium hydrogen persulfate 69mg (0.11mmol) and potassium bromide 3.5mg (0.025mmol).After the reaction was continued 1 day,
Intermediate is completely converted into product.Stop reaction, filtering, filtrate be added 30mL water, be extracted with ethyl acetate reaction solution (15mL ×
3), combined ethyl acetate extract liquor is added anhydrous magnesium sulfate and dries, filters, purified after concentration with silica gel column chromatography, eluted
Agent is petroleum ether: ethyl acetate (8:1) obtains yellow solid 2- acetyl furan naphthoquinones (compound 1), yield 100%.
mp.226.7-227.5℃。1HNMR(400MHz,CDCl3):δ:8.26(m,2H),7.81(m,2H),7.61(s,1H),2.66
(s,3H).
Embodiment 2
2- ethyl furan naphthoquinones 230mg (1mmol) is added in single neck bottle, completely, over cure is added in tetrahydrofuran 21mL dissolution
Potassium hydrogen phthalate 2.08g (3.3mmol) and potassium bromide 90mg (0.75mmol).After 45 DEG C are reacted 2 days, TLC detects raw material fully reacting.
Stop reaction, ethyl acetate extraction (50mL × 3) is added in addition water 30mL dilution, and it is dry to merge organic layer addition anhydrous sodium sulfate
It is dry, it is spin-dried for solvent, crosses column purification (PE/EA=3:1), obtains yellow solid 2,4.
2:mp.140.2-142.3 DEG C of compound,1H NMR(400MHz,CDCl3):δ:8.21(m,2H),7.57(m,2H),
6.85 (s, 1H), 5.04 (m, 1H), 1.65 (d, J=6.4Hz, 3H).
4:mp.247-248 DEG C of compound,1H NMR(500MHz,CDCl3)δ8.29–8.16(m,2H),7.83–7.73(m,
2H), 6.95 (s, 1H), 5.32-5.23 (m, 1H), 2.15 (dd, J=7.0,2.4Hz, 3H)；13C NMR(100MHz,CDCl3)δ
180.3,173.3,161.9,151.9,134.1,133.9,132.9,132.5,131.1,127.0,127.0,105.2,36.6,
23.5；HRMS(ESI)m/z[M+H]+calcd.ForC14H9BrO3,303.9735,found:304.9811。
Embodiment 3
23mg (0.1mmol) 2- ethyl furan naphthoquinones is dissolved in 6mL acetonitrile and 1mL water, and potassium hydrogen persulfate 139mg is added
(0.22mmol) and potassium bromide 6mg (0.05mmol).After 45 DEG C are reacted 1 day, TLC shows that raw material completely disappears, and occurs in part
Mesosome 2 and 4 largely remains in intermediate after the reaction was continued 1 day.Stop reaction, filtering, filtrate is added 30mL water, uses second
Acetoacetic ester extracts reaction solution (15mL × 3) combined ethyl acetate extract liquor, and anhydrous magnesium sulfate is added and dries, filters, uses after concentration
Silica gel column chromatography is purified, and eluant, eluent is petroleum ether: ethyl acetate (8:1), is obtained yellow intermediate (2,4), yield 42%, yellow
Color solid 1, yield 20%.
Embodiment 4
23mg (0.1mmol) 2- ethyl furan naphthoquinones is dissolved in 6mL acetonitrile and 1mL water, and potassium hydrogen persulfate 208mg is added
(0.33mmol) and potassium bromide 11mg (0.075mmol).After 45 DEG C are reacted 1 day, TLC shows that raw material completely disappears, and occurs a large amount of 2
With 4, after the reaction was continued 1 day, most of product 1 that generates stops reaction, filtering, and filtrate is added 30mL water, is extracted with ethyl acetate
Reaction solution (15mL × 3) combined ethyl acetate extract liquor is added anhydrous magnesium sulfate and dries, filters, silica gel column chromatography is used after concentration
Purified, eluant, eluent is petroleum ether: ethyl acetate (8:1) obtains yellow intermediate (2,4), yield 10%, yellow solid 1, produces
Rate 66%.
Embodiment 5
23mg (0.1mmol) 2- ethyl furan naphthoquinones is dissolved in 6mL acetonitrile and 1mL water, and potassium hydrogen persulfate 208mg is added
(0.33mmol) and potassium bromide 9mg (0.075mmol).After 0 DEG C is reacted 1 day, there is a small amount of intermediate 2 and 4, the reaction was continued 1 day
Afterwards, no significant change.Stop reaction, filtering, 30mL water is added in filtrate, and reaction solution (15mL × 3) merging is extracted with ethyl acetate
Acetic acid ethyl acetate extract is added anhydrous magnesium sulfate and dries, filters, purified after concentration with silica gel column chromatography, eluant, eluent is stone
Oily ether: ethyl acetate (8:1) obtains yellow intermediate (2,4), yield 35%.
Embodiment 6
The preparation of Avicennia marina quinone C (compound 3,2- (2- hydroxyl propyl- 2- yl) naphtho- [2,3-b] furans -4,9- diketone)
24mg (0.1mmol) 2- propyl furans naphthoquinones is dissolved in 6mL acetonitrile and 1mL water, and potassium hydrogen persulfate 139mg is added
(0.22mmol) and potassium bromide 6mg (0.05mmol).After 45 DEG C are reacted 1 day, TLC shows that raw material completely disappears, and generates product.Stop
It only reacting, filters, 30mL water is added in filtrate, reaction solution (15mL × 3) combined ethyl acetate extract liquor is extracted with ethyl acetate,
Anhydrous magnesium sulfate is added to dry, filter, is purified after concentration with silica gel column chromatography, eluant, eluent is petroleum ether: ethyl acetate (3:
1) yellow Avicennia marina quinone C (compound 3), is obtained, yield 95%, mp.256-257 DEG C, 1H NMR (500MHz, CDCl3) δ 8.25-
8.14 (m), 7.81-7.71 (m), 6.85 (d, J=4.1Hz), 1.72 (s) .13C NMR (100MHz, CDCl3) δ 180.8,
173.5,168.0,151.8,134.0,133.8,133.0,132.5,131.3,127.0,126.9,102.6,69.4,28.8。
Experiment condition inquires into 1
In mass ratio, feed ratio is determined in raw material: potassium hydrogen persulfate: potassium bromide=1:3.3:0.75, temperature determine
45 DEG C, the reaction time is determined as 2 days, and different solvents are discussed and its with the influence for comparing yield, the conditions such as discovery solvent are to reaction
There is certain influence.Its partial results is as shown in table 1.
Influence of 1 solvent of table to reaction
Wherein, DCM indicates that methylene chloride, THF indicate tetrahydrofuran, MeNO2Indicate nitromethane.
Experiment condition inquires into 2
In mass ratio, feed ratio is raw material: potassium hydrogen persulfate: the volume proportion of potassium bromide=1:3.3:0.75, solvent is
CH3CN:H2O=6/1, time are 2 days, and the results are shown in Table 2 for influence of the temperature to yield, when temperature is 0 DEG C, yield 35%；
When temperature is 45 DEG C, it is completely converted into product 1, i.e., its yield is 100%；When temperature is 60 DEG C, reaction product is complicated, does not separate
Compound 2,4 and 1 out.
Influence of 2 temperature of table to reaction
Claims (8)
1. a kind of method for synthesizing benzofuran naphthoquinone derivatives, which is characterized in that withFor raw material,
Under hydrogen persulfate radical ion and bromide ion effect, oxidation reaction is carried out in solvent and obtains benzofuran naphthoquinone derivatives；Wherein,
Having one or two substituent group in R1, R2 and R3 is H atom, remaining substituent group is methyl；The benzofuran naphthoquinones is derivative
Object includes:
2. the method as described in claim 1, which is characterized in that the hydrogen persulfate radical ion is provided by potassium hydrogen persulfate；Institute
Bromide ion is stated to be provided by potassium bromide.
3. the method as described in claim 1, which is characterized in that the temperature of the oxidation reaction is 0-50 DEG C.
4. the method as described in claim 1, which is characterized in that the temperature of the oxidation reaction is 30-50 DEG C.
5. the method as described in claim 1, which is characterized in that the solvent is the mixed solvent that water and organic solvent form.
6. method as claimed in claim 5, which is characterized in that the volume ratio of the organic solvent and water is 12:(1-4).
7. the method as described in claim 1, which is characterized in that the molar ratio of the hydrogen sulfate ion and raw material is (2-4):
1。
8. the method as described in claim 1, which is characterized in that the molar ratio of the bromide ion and raw material is (0.5-1): 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610756212.1A CN106380456B (en) | 2016-08-29 | 2016-08-29 | A method of synthesis benzofuran naphthoquinone derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610756212.1A CN106380456B (en) | 2016-08-29 | 2016-08-29 | A method of synthesis benzofuran naphthoquinone derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106380456A CN106380456A (en) | 2017-02-08 |
| CN106380456B true CN106380456B (en) | 2019-03-26 |
Family
ID=57917418
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610756212.1A Expired - Fee Related CN106380456B (en) | 2016-08-29 | 2016-08-29 | A method of synthesis benzofuran naphthoquinone derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106380456B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109988157B (en) * | 2018-01-03 | 2022-12-27 | 四川大学 | Novel small molecular compound, preparation method and application in preparation of drug-resistant mycobacterium tuberculosis and other mycobacteria drugs |
| CN107973788B (en) * | 2018-01-09 | 2021-07-09 | 沈阳药科大学 | BBI608 derivative and preparation and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003093171A1 (en) * | 2002-05-06 | 2003-11-13 | Bromine Compounds Ltd. | Process for the preparation of concentrated solutions of stabilized hypobromites |
| CN104586832A (en) * | 2007-09-10 | 2015-05-06 | 北京强新生物科技有限公司 | Novel compositions and methods for cancer treatment |
| CN105272953A (en) * | 2015-10-29 | 2016-01-27 | 中南大学 | Method for synthesizing coumarone naphthoquinone derivative |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015030699A (en) * | 2013-08-02 | 2015-02-16 | マナック株式会社 | Oxidative debenzylation reaction of benzyl amine and benzyl ether using alkali metal halide |
-
2016
- 2016-08-29 CN CN201610756212.1A patent/CN106380456B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003093171A1 (en) * | 2002-05-06 | 2003-11-13 | Bromine Compounds Ltd. | Process for the preparation of concentrated solutions of stabilized hypobromites |
| CN104586832A (en) * | 2007-09-10 | 2015-05-06 | 北京强新生物科技有限公司 | Novel compositions and methods for cancer treatment |
| CN105272953A (en) * | 2015-10-29 | 2016-01-27 | 中南大学 | Method for synthesizing coumarone naphthoquinone derivative |
Non-Patent Citations (5)
| Title |
|---|
| 2-乙酰基呋喃萘醌及其衍生物抗肿瘤作用的研究进展;谢朵朵，等;《中南药学》;20140228;第12卷(第2期);第148-151页 |
| A Facile Synthesis of 2-Acetylnaphtho[2,3-b]furan-4,9-dione;Jyunichi Koyanagi，等;《J. Heterocyclic Chem.》;19951231;第32卷;第1290-1291页 |
| A New Synthetic Route to 2-Substituted Naphtho[2,3-b]furan-4,9-dione;Jyunichi Koyanagi，等;《J. Heterocyclic Chem.》;19971231;第34卷;第407-412页 |
| A short-step Synthesis of Naphtho[2,3-b]furan-4,9-dione;Jyunichi Koyanagi，等;《J. Heterocyclic Chem.》;19941231;第31卷;1303-1304页 |
| Dual oxidation/bromination of alkylbenzenes;Marwa M. Aborways，等;《Tetrahedron Letters》;20160122;第57卷(第9期);第984页表1-2、图1，第985页结论部分 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106380456A (en) | 2017-02-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Luo et al. | Miscellaneous meroterpenoids from Ganoderma applanatum | |
| Wu et al. | Xyloccensins Q–V, six new 8, 9, 30-phragmalin ortho ester antifeedants from the Chinese mangrove Xylocarpus granatum | |
| Chiang et al. | Two novel α-tocopheroids from the aerial roots of Ficus microcarpa | |
| Li et al. | Absolute configuration, conformation, and chiral properties of flavanone-(3→ 8 ″)-flavone biflavonoids from Rheedia acuminata | |
| Anuradha et al. | Isolation and synthesis of analgesic and anti-inflammatory compounds from Ochna squarrosa L. | |
| Sun et al. | New bromopyrrole alkaloids from the marine sponge Agelas sp. | |
| CN106380456B (en) | A method of synthesis benzofuran naphthoquinone derivatives | |
| Jiang et al. | Brominated polyunsaturated lipids and their stereochemistry from the Chinese marine sponge Xestospongia testudinaria | |
| CN107312055A (en) | A kind of new preparation method of rocuronium | |
| Mishchenko et al. | Mirabiquinone, a new unsymmetrical binaphthoquinone from the sea urchin Scaphechinus mirabilis | |
| Homer et al. | A short synthesis of the endogenous plant metabolite 7-hydroxyoxindole-3-acetic acid (7-OH-OxIAA) using simultaneous C–H borylations | |
| Wu et al. | Ivorenoids A–F: limonoids from Khaya ivorensis | |
| Zhang et al. | A new cinnamamide derivative and two new β-carboline alkaloids from the stems of Picrasma quassioides | |
| Choi et al. | Synthesis of 6, 6-bisbenzannulated spiroketals related to the rubromycins using a double intramolecular hetero-Michael addition (DIHMA) | |
| Parasuraman et al. | Stereoselective synthesis of substituted 1, 2-annulated sugars by domino double-Michael addition reaction | |
| Al-Musayeib et al. | Labdane diterpenes from Otostegia fruticosa | |
| Li et al. | Unusual inner-salt guaiazulene alkaloids and bis-sesquiterpene from the south china sea gorgonian muriceides collaris | |
| Hu et al. | Seven new anthranilamide derivatives from Aconitum apetalum | |
| Fernández et al. | Isolation of naturally occurring dactylomelane metabolites as Laurencia constituents | |
| Mazzini et al. | Easy route to labeled and unlabeled R, R, R-γ-tocopherol by aryl demethylation of α-homologues | |
| Wang et al. | Two pairs of new benzofuran enantiomers with unusual skeletons from Eupatorium chinense | |
| Magnusson et al. | Synthesis of enantiomerically pure (Z)-(2′ R)-1-O-(2′-methoxyhexadec-4′-enyl)-sn-glycerol present in the liver oil of cartilaginous fish | |
| Chen et al. | Ochuscins A‒G, highly oxygenated usnic acid derivatives from the deep-sea-derived fungus Ochroconis sp. FS449 | |
| Yang et al. | New nonadjacent bis-THF ring acetogenins from the seeds of Annona squamosa | |
| NO322266B1 (en) | Taxane derivatives, their preparation and formulations containing them |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20190326 Termination date: 20190829 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |