CN102134247A - Xanthotoxol derivative and new composite method thereof - Google Patents
Xanthotoxol derivative and new composite method thereof Download PDFInfo
- Publication number
- CN102134247A CN102134247A CN 201110021826 CN201110021826A CN102134247A CN 102134247 A CN102134247 A CN 102134247A CN 201110021826 CN201110021826 CN 201110021826 CN 201110021826 A CN201110021826 A CN 201110021826A CN 102134247 A CN102134247 A CN 102134247A
- Authority
- CN
- China
- Prior art keywords
- xanthotoxol
- derivative
- structure shown
- chemical formula
- milliliters
- 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
- JWVYQQGERKEAHW-UHFFFAOYSA-N xanthotoxol Chemical class C1=CC(=O)OC2=C1C=C1C=COC1=C2O JWVYQQGERKEAHW-UHFFFAOYSA-N 0.000 title claims abstract description 65
- 238000000034 method Methods 0.000 title abstract description 8
- 239000002131 composite material Substances 0.000 title abstract 2
- 239000000126 substance Substances 0.000 claims abstract description 50
- GIJHDGJRTUSBJR-UHFFFAOYSA-N Bergaptol Natural products O1C(=O)C=CC2=C1C=C1OC=CC1=C2O GIJHDGJRTUSBJR-UHFFFAOYSA-N 0.000 claims abstract description 44
- YXCORZFYRFZUOV-UHFFFAOYSA-N Xanthotoxol Natural products COc1c2OC(O)C=Cc2cc3ccoc13 YXCORZFYRFZUOV-UHFFFAOYSA-N 0.000 claims abstract description 44
- 238000002360 preparation method Methods 0.000 claims abstract description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 36
- 239000001257 hydrogen Substances 0.000 claims abstract description 36
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 30
- 150000001875 compounds Chemical class 0.000 claims abstract description 25
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 239000000203 mixture Substances 0.000 claims abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 230000018044 dehydration Effects 0.000 claims description 2
- 238000006297 dehydration reaction Methods 0.000 claims description 2
- 238000006356 dehydrogenation reaction Methods 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 84
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- 150000002596 lactones Chemical class 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 89
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
- 239000012044 organic layer Substances 0.000 description 60
- 235000019441 ethanol Nutrition 0.000 description 41
- 238000001953 recrystallisation Methods 0.000 description 39
- 238000005406 washing Methods 0.000 description 37
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- 239000003643 water by type Substances 0.000 description 32
- 239000003921 oil Substances 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 238000000605 extraction Methods 0.000 description 29
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 28
- 238000010792 warming Methods 0.000 description 28
- 238000003756 stirring Methods 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
- BUNGCZLFHHXKBX-UHFFFAOYSA-N 9-methoxy-2,3-dihydrofuro[3,2-g]chromen-7-one Chemical compound C1=CC(=O)OC2=C1C=C1CCOC1=C2OC BUNGCZLFHHXKBX-UHFFFAOYSA-N 0.000 description 16
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- QXKHYNVANLEOEG-UHFFFAOYSA-N Methoxsalen Chemical compound C1=CC(=O)OC2=C1C=C1C=COC1=C2OC QXKHYNVANLEOEG-UHFFFAOYSA-N 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 13
- PCWZKQSKUXXDDJ-UHFFFAOYSA-N Xanthotoxin Natural products COCc1c2OC(=O)C=Cc2cc3ccoc13 PCWZKQSKUXXDDJ-UHFFFAOYSA-N 0.000 description 12
- 229960004469 methoxsalen Drugs 0.000 description 12
- SQBBOVROCFXYBN-UHFFFAOYSA-N methoxypsoralen Natural products C1=C2OC(=O)C(OC)=CC2=CC2=C1OC=C2 SQBBOVROCFXYBN-UHFFFAOYSA-N 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 238000005984 hydrogenation reaction Methods 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 229940017219 methyl propionate Drugs 0.000 description 9
- 239000002994 raw material Substances 0.000 description 9
- AKTDHHFJFNIILG-UHFFFAOYSA-N 3,3-diethoxypropanoic acid Chemical compound CCOC(CC(O)=O)OCC AKTDHHFJFNIILG-UHFFFAOYSA-N 0.000 description 8
- GWDMSCZQYHAETO-UHFFFAOYSA-N 9-hydroxy-2,3-dihydrofuro[3,2-g]chromen-7-one Chemical compound C1=CC(=O)OC2=C1C=C1CCOC1=C2O GWDMSCZQYHAETO-UHFFFAOYSA-N 0.000 description 8
- 125000005605 benzo group Chemical group 0.000 description 8
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 8
- OAKURXIZZOAYBC-UHFFFAOYSA-N 3-oxopropanoic acid Chemical compound OC(=O)CC=O OAKURXIZZOAYBC-UHFFFAOYSA-N 0.000 description 7
- 239000012141 concentrate Substances 0.000 description 7
- 238000000967 suction filtration Methods 0.000 description 7
- 238000011084 recovery Methods 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 239000007790 solid phase Substances 0.000 description 5
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 4
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 4
- 229940079877 pyrogallol Drugs 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000007039 two-step reaction Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000003963 dichloro group Chemical group Cl* 0.000 description 2
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 2
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- QYEVTADDYREVHU-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-6,7-diol Chemical class OC1=CC=C2CCOC2=C1O QYEVTADDYREVHU-UHFFFAOYSA-N 0.000 description 1
- FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 1
- 244000061520 Angelica archangelica Species 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 0 COc(ccc1c2OCC1)c2O* Chemical compound COc(ccc1c2OCC1)c2O* 0.000 description 1
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 1
- 240000008384 Capsicum annuum var. annuum Species 0.000 description 1
- 241000212941 Glehnia Species 0.000 description 1
- 235000001287 Guettarda speciosa Nutrition 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 241001093501 Rutaceae Species 0.000 description 1
- 206010047642 Vitiligo Diseases 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 229940027035 oxsoralen Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 239000001229 ruta graveolens Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- -1 unsaturated cyclic lactone Chemical class 0.000 description 1
Abstract
The invention discloses a xanthotoxol derivative and a new composite method thereof, belonging to the filed of organic chemistry and pharmaceutical chemistry. The xanthotoxol derivative has a structure shown by a chemical formula (1), wherein R1 represents hydrogen or alkyl. The xanthotoxol and the xanthotoxol derivative with a structure shown by a chemical formula (III) can be prepared from a compound with a structure shown by the chemical formula (I) by further reaction. The invention simultaneously provides multiple preparation methods of xanthotoxol and xanthotoxol derivatives with structures shown by chemical formulae (I), (II), (III); the method takes cyclization reaction as a key step to prepare the xanthotoxol and the xanthotoxol derivatives, the cyclization method can form the needed hexahydric unsaturated ring lactone by further reaction, the operation is simple, and the efficiency is high. The preparation method is simple, has low material cost, less composition steps, and high production yield, is simple and safe in operation, and is applicable to industrialized production.
Description
Technical field
The present invention relates to the novel synthesis of a kind of xanthotoxol and xanthotoxol and derivative thereof, belong to organic chemistry and pharmaceutical chemistry field.
Background technology
Xanthotoxol is golden yellow or cream-coloured crystallization, has structure shown in following chemical formula (III),
Wherein, R
3Represent hydrogen.
Xanthotoxol has anti-inflammatory and analgesic activity preferably, also has anti-arrhythmia, brings high blood pressure down, effects such as osteoporosis, eliminating phlegm and relieving asthma.In addition, xanthotoxol all demonstrates anti-oxidant activity in lipid peroxidation test and hemolytic test.
Xanthotoxin claims ammoidin again, or oxsoralen, is the derivative of xanthotoxol.Its proterties is white or faint yellow crystallization, has structure shown in following chemical formula (III),
Wherein, R
3Represent methylidene.
Xanthotoxin has spasmolysis, anti-microbial effect, and ehrlich's ascite cell is had killing action, is used for the treatment of stenocardia, vitiligo, psoriasis and psoriatic clinically.
The plant origin of xanthotoxol has rhizome or fruits such as Fructus Cnidii, the root of Dahurain angelica, Root of coastal Glehnia, notopterygium root.The plant origin of xanthotoxin mainly contains the fruit of rutaceae precipice green pepper, rue herb etc.But their extraction separation from natural phant are subjected to resource limit, and output is limited.The organic synthesis of xanthotoxol and xanthotoxin appears in the newspapers, but the synthetic route of most of bibliographical informations is tediously long, and total recovery is low.Carl (Acta Chem. Scand. 1956,10 (4), 647-654.), Seshadri(Indian J. Chem.1963,292 (1), 291-294.), Souza(J. Heterocycl. Chem. 1966,42 (3), 42-45.) with Mansumi(J. Indian Chem. Soc. 1999,76 (11), 551-556.) reported the synthetic method of several xanthotoxols and xanthotoxin.But total recovery all is no more than 5%.2006, and Wang Laiyou (Chinese pharmaceutical chemistry magazine, 2006,14 (3), 154-157.) having reported a kind of is raw material with the pyrogallol, through the synthetic method of 9 step prepared in reaction xanthotoxins.Though total recovery brings up to 9%, reactions steps is longer.
For the raw material of energy mass production, be necessary to study a kind of novel synthesis that is fit to industrial xanthotoxol and derivative thereof as pharmaceutical preparation.
Summary of the invention
The purpose of this invention is to provide a kind of new xanthotoxol derivative and the novel synthesis that is applicable to suitability for industrialized production of xanthotoxol and derivative thereof.
For achieving the above object, the technical solution used in the present invention is:
New xanthotoxol derivative of the present invention has structure shown in chemical formula (I),
Wherein, R
1Represent hydrogen or alkyl.
The preparation method of this xanthotoxol derivative of the present invention is: the compound that will have a structure shown in chemical formula (IV) and compound with structure shown in chemical formula V, have any one in the compound of structure shown in chemical formula (VI) or appoint several mixtures carry out ring-closure reaction prepare as described in the xanthotoxol derivative
Wherein, R
4, R
5, R
6, R
7, R
8Represent hydrogen or alkyl independently of one another.
The preparation method of xanthotoxol derivative of the present invention is: the compound that will have a structure shown in chemical formula (VII) and compound with structure shown in chemical formula V, have any one in the compound of structure shown in chemical formula (VI) or appoint several mixtures carry out ring-closure reaction prepare as described in the xanthotoxol derivative, described xanthotoxol derivative has structure shown in chemical formula (II)
Wherein, R
2, R
5, R
6, R
7, R
8, R
9Represent hydrogen or alkyl independently of one another
The preparation method of xanthotoxol of the present invention and derivative thereof is: the compound that will have a structure shown in chemical formula (VIII) and compound with structure shown in chemical formula V, have shown in chemical formula (VI) any one in the structural compounds or appoint several mixtures carry out ring-closure reaction prepare as described in xanthotoxol and derivative thereof, described xanthotoxol and derivative thereof have structure shown in chemical formula (III)
Wherein, R
3, R
5, R
6, R
7, R
8, R
10Represent hydrogen or alkyl independently of one another.
The preparation method of xanthotoxol of the present invention and derivative thereof is: the compound that will have a structure shown in chemical formula (I) is earlier after xanthotoxol and derivative thereof as described in preparing behind the carbonyl reduction, dehydration, described xanthotoxol and derivative thereof have structure shown in chemical formula (III)
Wherein, R
1, R
3Represent hydrogen or alkyl independently of one another.
The preparation method of xanthotoxol of the present invention and derivative thereof is: the compound that will have a structure shown in chemical formula (I) earlier through hydro-reduction, again through dehydrogenation prepare as described in xanthotoxol and derivative thereof, described xanthotoxol and derivative thereof have structure shown in chemical formula (III)
Wherein, R
1, R
3Represent hydrogen or alkyl independently of one another.
Compared with prior art, the invention has the beneficial effects as follows: (1) the invention discloses a kind of new xanthotoxol derivant structure (shown in Formula I), and discloses several methods that had the xanthotoxol derivative of structure shown in the formula III by the compound with structure shown in the formula I simultaneously.Among the present invention, the xanthotoxol of structure and derivative thereof can obtain from the compound with structure shown in the Formula I by single step reaction shown in Formulae II I.(2) the present invention provides several preparation methods with xanthotoxol and the derivative thereof of structure shown in Formula I, II or the III simultaneously.It is that committed step prepares xanthotoxol and derivative thereof with the ring-closure reaction.This cyclization method promptly forms required hexa-atomic unsaturated cyclic lactone through single step reaction, and is simple to operate, the efficient height.With the xanthotoxol is example, adopts preparation method of the present invention, is raw material with the pyrogallol, and reactions steps can reduce to for 4 steps, and overall yield Gao Keda 27%.(3) the raw materials used cost of preparation method of the present invention is low, and synthesis step is short, safety simple to operate, and the product yield height is applicable to suitability for industrialized production.
Embodiment
The invention will be further described below by example, but do not limit the present invention.
Below each embodiment about xanthotoxol and (or) employed raw material 6 in the preparation process of its derivative, 7-dihydroxyl benzo furans-3 (2H)-ketone and 6-hydroxyl-7-alkoxyl group-cumarone-3 (2H)-ketone can the reference literature method (for example, document 1.Venkateswarlu, Somepalli; Panchagnula, Gopala K.; Subbaraju, Gottumukkala V.
Bioscience, Biotechnology, and Biochemistry2004,
68, 2183-2185. and document 2. Thomas, Michael G.; Lawson, Chris; Allanson, Nigel M.; Leslie, Bruce W.; Bottomley, Joanna R.; McBride, Andrew; Olusanya, Oyinkan A.
Bioorganic ﹠amp; Medicinal Chemistry Letters2003,
13, 423-426.), respectively with pyrogallol or 2-alkoxyl group-1, to be raw material make through two-step reaction is corresponding the 3-dihydroxy-benzene.Wherein, according to the method for Venkateswarlu (
Bioscience, Biotechnology, and Biochemistry2004,
68, 2183-2185.), be raw material with the pyrogallol, make 6 through two-step reaction, 7-dihydroxyl benzo furans-3 (2H)-ketone, total recovery is 43%.With 2-methoxyl group-1, the 3-dihydroxy-benzene is a raw material, makes 6-hydroxyl-7-methoxyl group-cumarone-3 (2H)-ketone through two-step reaction, and total recovery is 41%.With 2-oxyethyl group-1, the 3-dihydroxy-benzene is a raw material, makes 6-hydroxyl-7-oxyethyl group-cumarone-3 (2H)-ketone through two-step reaction, and total recovery is 38%.
Embodiment 1: 9-hydroxyl-2H-furo [3,2-g] chromene-3, the 7-diketone (has structure shown in the Formula I, wherein R
1
Be hydrogen) preparation
In reaction flask, add 22 grams 6,7-dihydroxyl benzo furans-3 (2H)-ketone (have structure shown in Formula I V, wherein, R
4Be hydrogen), 28 grams 3,3-diethoxy propionic acid (having suc as formula structure shown in the V) stirs, and adds 20 milliliters of trifluoroacetic acids and 14 milliliters of vitriol oils as solvent.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 20 gram 9-hydroxyl-2H-furo [3,2-g] chromenes-3,7-diketone through ethyl alcohol recrystallization.Productive rate is 69%.HREIMS m/z 218.0222 (C
11H
6O
5, calculated value: 218.0215).
Embodiment 2:9-hydroxyl-2H-furo [3,2-g] chromene-3, the 7-diketone (has structure shown in the Formula I, wherein R
1
Be hydrogen) preparation
In reaction flask, add 22 grams 6,7-dihydroxyl benzo furans-3 (2H)-ketone, 25 grams 3,3-dimethoxy methyl propionate (having suc as formula structure shown in the V) stirs, and adds 20 milliliters of trifluoroacetic acids and 14 milliliters of vitriol oils as solvent.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 19 gram 9-hydroxyl-2H-furo [3,2-g] chromenes-3,7-diketone through ethyl alcohol recrystallization.Productive rate is 66%.HREIMS m/z 218.0230 (C
11H
6O
5, calculated value: 218.0215).
Embodiment 3:9-hydroxyl-2H-furo [3,2-g] chromene-3, the 7-diketone (has structure shown in the Formula I, wherein R
1
Be hydrogen) preparation
In reaction flask, add 22 grams 6,7-dihydroxyl benzo furans-3 (2H)-ketone, 21 gram 3-oxo propionic acid (having suc as formula structure shown in the VI) stir, and add 20 milliliters of trifluoroacetic acids and 14 milliliters of vitriol oils as solvent.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then.Organic layer is with after the saturated common salt water washing, is concentrated into driedly, gets 20 gram 9-hydroxyl-2H-furo [3,2-g] chromenes-3,7-diketone through ethyl alcohol recrystallization.Productive rate is 69%.HREIMS m/z 218.0206 (C
11H
6O
5, calculated value: 218.0215).
Embodiment 4:9-hydroxyl-2H-furo [3,2-g] chromene-3, the 7-diketone (has structure shown in the Formula I, wherein R
1
Be hydrogen) preparation
In reaction flask, add 22 grams 6,7-dihydroxyl benzo furans-3 (2H)-ketone, 25 gram 3-oxo methyl propionates (having suc as formula structure shown in the VI) stir, and add 20 milliliters of trifluoroacetic acids and 14 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then.Organic layer is with after the saturated common salt water washing, is concentrated into driedly, gets 16 gram 9-hydroxyl-2H-furo [3,2-g] chromenes-3,7-diketone through ethyl alcohol recrystallization.Productive rate is 55%.HREIMS m/z 218.0226 (C
11H
6O
5, calculated value: 218.0215).
Embodiment 5:9-methoxyl group-2H-furo [3,2-g] chromene-3, the 7-diketone (has structure shown in the Formula I, wherein R
1
Be methyl) preparation
In reaction flask, and adding 23 gram 6-hydroxyl-7-methoxyl group-cumarone-3 (2H)-ketone (have structure shown in Formula I V, wherein, R
4Be methyl), 28 grams 3,3-diethoxy propionic acid stirs, and adds 20 milliliters of trifluoroacetic acids and 14 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 20 gram 9-methoxyl group-2H-furo [3,2-g] chromenes-3,7-diketone through ethyl alcohol recrystallization.Productive rate is 67%.HREIMS m/z 232.0356 (C
12H
8O
5, calculated value: 232.0372).
Embodiment 6:9-oxyethyl group-2H-furo [3,2-g] chromene-3, the 7-diketone (has structure shown in the Formula I, wherein R
1
Be ethyl) preparation
In reaction flask, add 25 gram 6-hydroxyl-7-oxyethyl group-cumarone-3 (2H)-ketone, 25 grams 3,3-dimethoxy methyl propionate stirs, and adds 20 milliliters of trifluoroacetic acids and 14 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 20 gram 9-oxyethyl group-2H-furo [3,2-g] chromenes-3,7-diketone through ethyl alcohol recrystallization.Productive rate is 63%.HREIMS m/z 246.0533 (C
12H
8O
5, calculated value: 246.0528).
Embodiment 7:9-methoxyl group-2H-furo [3,2-g] chromene-3, the 7-diketone (has structure shown in the Formula I, wherein R
1
Be methyl) preparation
In reaction flask, add 23 gram 6-hydroxyl-7-methoxyl group-cumarone-3 (2H)-ketone, 21 gram 3-oxo propionic acid stir, and add 20 milliliters of trifluoroacetic acids and 14 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then.Organic layer is with after the saturated common salt water washing, is concentrated into driedly, gets 19 gram 9-methoxyl group-2H-furo [3,2-g] chromenes-3,7-diketone through ethyl alcohol recrystallization.Productive rate is 64%.HREIMS m/z 232.0365 (C
12H
8O
5, calculated value: 232.0372).
Embodiment 8:9-oxyethyl group-2H-furo [3,2-g] chromene-3, the 7-diketone (has structure shown in the Formula I, wherein R
1
Be ethyl) preparation
In reaction flask, add 25 gram 6-hydroxyl-7-oxyethyl group-cumarone-3 (2H)-ketone, 25 gram 3-oxo methyl propionates stir, and add 20 milliliters of trifluoroacetic acids and 14 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then.Organic layer is with after the saturated common salt water washing, is concentrated into driedly, gets 25 gram 9-oxyethyl group-2H-furo [3,2-g] chromenes-3,7-diketone through ethyl alcohol recrystallization.Productive rate is 78%.HREIMS m/z 246.0536 (C
12H
8O
5, calculated value: 246.0528).
Related 6 in following examples 9-12,7-dihydroxyl-2, the 3-Dihydrobenzofuranes (have structure shown in chemical formula VII, wherein, R
9
Be hydrogen) can make by following hydrogenation, specific as follows:
In reaction flask, add 150 grams 6,7-dihydroxyl benzo furans-3 (2H)-ketone (Formula I V, R
4Be hydrogen), 300 gram acetic acid, 1 kilogram of ethanol, 50 grams, 5% palladium carbon.Hydrogenation 24 hours.TLC reacts completely, and suction filtration is removed palladium carbon, gets 105 grams 6,7-dihydroxyl-2,3-Dihydrobenzofuranes (chemical formula VII, R after filtrate concentrates
9Be hydrogen).Productive rate is 76%.
Embodiment 9: by ring-closure reaction preparation 2,3-dihydro-xanthotoxol (Formulae II, R
2
Be hydrogen)
In reaction flask, add 20 grams 6,7-dihydroxyl-2, the 3-Dihydrobenzofuranes, 28 grams 3,3-diethoxy propionic acid stirs, and adds 20 milliliters of trifluoroacetic acids and 14 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 19 grams 2,3-dihydro-xanthotoxol through ethyl alcohol recrystallization.Productive rate is 71%.HREIMS m/z 204.0439 (C
11H
8O
4, calculated value: 204.0423).
Embodiment 10: by ring-closure reaction preparation 2,3-dihydro-xanthotoxol (Formulae II, R
2
Be hydrogen)
In reaction flask, add 20 grams 6,7-dihydroxyl-2, the 3-Dihydrobenzofuranes, 25 grams 3,3-dimethoxy methyl propionate stirs, and adds 20 milliliters of trifluoroacetic acids and 14 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 16 grams 2,3-dihydro-xanthotoxol through ethyl alcohol recrystallization.Productive rate is 60%.HREIMS m/z 204.0429 (C
11H
8O
4, calculated value: 204.0423).
Embodiment 11: by ring-closure reaction preparation 2,3-dihydro-xanthotoxol (Formulae II, R
2
Be hydrogen)
In reaction flask, add 20 grams 6,7-dihydroxyl-2, the 3-Dihydrobenzofuranes, 21 gram 3-oxo propionic acid stir, and add 20 milliliters of trifluoroacetic acids and 14 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then.Organic layer is with after the saturated common salt water washing, is concentrated into driedly, gets 21 grams 2,3-dihydro-xanthotoxol through ethyl alcohol recrystallization.Productive rate is 78%.HREIMS m/z 204.0416 (C
11H
8O
4, calculated value: 204.0423).
Embodiment 12: by ring-closure reaction preparation 2,3-dihydro-xanthotoxol (Formulae II, R
2
Be hydrogen)
In reaction flask, add 20 grams 6,7-dihydroxyl-2, the 3-Dihydrobenzofuranes, 25 gram 3-oxo methyl propionates stir, and add 20 milliliters of trifluoroacetic acids and 14 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then.Organic layer is with after the saturated common salt water washing, is concentrated into driedly, gets 19 grams 2,3-dihydro-xanthotoxol through ethyl alcohol recrystallization.Productive rate is 71%.HREIMS m/z 204.0434 (C
11H
8O
4, calculated value: 204.0423).
Following examples 13-16 is related6-hydroxyl-7-methoxyl group-2,3-Dihydrobenzofuranes (chemical formula
VII, R
9Be methyl) can pass through below
Hydrogenation makes, and concrete grammar is as follows:
In reaction flask, add 320 gram 6-hydroxyl-7-methoxyl group-cumarone-3 (2H)-ketone (Formula I V, R
4Be methyl), 600 gram acetic acid, 2 kilograms of ethanol, 100 grams, 5% palladium carbon.Hydrogenation 24 hours.TLC reacts completely, and suction filtration is removed palladium carbon, gets 250 gram 6-hydroxyl-7-methoxyl groups-2 after filtrate concentrates, 3-Dihydrobenzofuranes (chemical formula VII, R
9Be methyl).Productive rate is 78%.
Embodiment 13: by ring-closure reaction preparation 2,3-dihydro-xanthotoxin (Formulae II, R
2
Be methyl)
In reaction flask, add 25 gram 6-hydroxyl-7-methoxyl groups-2,3-Dihydrobenzofuranes, 31 grams 3,3-diethoxy propionic acid and 23 milliliters of trifluoroacetic acids and 16 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 20 grams 2,3-dihydro-xanthotoxin through ethyl alcohol recrystallization.Productive rate is 61%.HREIMS m/z 218.0588 (C
12H
10O
4, calculated value: 218.0579).
Embodiment 14: by ring-closure reaction preparation 2,3-dihydro-xanthotoxin (Formulae II, R
2
Be methyl)
In reaction flask, add 25 gram 6-hydroxyl-7-methoxyl groups-2,3-Dihydrobenzofuranes, 29 grams 3,3-dimethoxy methyl propionate and 23 milliliters of trifluoroacetic acids and 16 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 21 grams 2,3-dihydro-xanthotoxin through ethyl alcohol recrystallization.Productive rate is 64%.HREIMS m/z 218.0592 (C
12H
10O
4, calculated value: 218.0579).
Embodiment 15: by ring-closure reaction preparation 2,3-dihydro-xanthotoxin (Formulae II, R
2
Be methyl)
In reaction flask, add 30 gram 6-hydroxyl-7-methoxyl groups-2,3-Dihydrobenzofuranes, 29 gram 3-oxo propionic acid and 28 milliliters of trifluoroacetic acids and 19 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 26 grams 2,3-dihydro-xanthotoxin through ethyl alcohol recrystallization.Productive rate is 66%.HREIMS m/z 218.0568 (C
12H
10O
4, calculated value: 218.0579).
Embodiment 16: by ring-closure reaction preparation 2,3-dihydro-xanthotoxin (Formulae II, R
2
Be methyl)
In reaction flask, add 30 gram 6-hydroxyl-7-methoxyl groups-2,3-Dihydrobenzofuranes, 35 gram 3-oxo methyl propionate and 28 milliliters of trifluoroacetic acids and 19 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 27 grams 2,3-dihydro-xanthotoxin through ethyl alcohol recrystallization.Productive rate is 68%.HREIMS m/z 218.0583 (C
12H
10O
4, calculated value: 218.0579).
Following examples 17-18 is related6-hydroxyl-7-oxyethyl group-2,3-Dihydrobenzofuranes (chemical formula
VII, R
9Be ethyl) can pass through below
Hydrogenation makes, and concrete grammar is as follows:
In reaction flask, add 300 gram 6-hydroxyl-7-oxyethyl group-cumarone-3 (2H)-ketone (Formula I V, R
4Be ethyl), 522 gram acetic acid, 1.7 kilograms of ethanol, 87 grams, 5% palladium carbon.Hydrogenation 24 hours.TLC reacts completely, and suction filtration is removed palladium carbon, gets 207 gram 6-hydroxyl-7-methoxyl groups-2 after filtrate concentrates, 3-Dihydrobenzofuranes (chemical formula VII, R
9Be ethyl).Productive rate is 75%.
Embodiment 17: prepare 8-oxyethyl group-2 by ring-closure reaction, 3-dihydro-psoralene (Formulae II, R
2
Be ethyl)
In reaction flask, add 28 gram 6-hydroxyl-7-oxyethyl groups-2,3-Dihydrobenzofuranes, 31 grams 3,3-diethoxy propionic acid and 23 milliliters of trifluoroacetic acids and 16 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 24 gram 8-oxyethyl groups-2,3-dihydro-psoralene through ethyl alcohol recrystallization.Productive rate is 67%.HREIMS m/z 232.0742 (C
12H
10O
4, calculated value: 232.0736).
Embodiment 18: prepare 8-oxyethyl group-2 by ring-closure reaction, 3-dihydro-psoralene (Formulae II, R
2
Be ethyl)
In reaction flask, add 32 gram 6-hydroxyl-7-methoxyl groups-2,3-Dihydrobenzofuranes, 29 gram 3-oxo propionic acid and 28 milliliters of trifluoroacetic acids and 19 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 29 gram 8-oxyethyl groups-2,3-dihydro-psoralene through ethyl alcohol recrystallization.Productive rate is 70%.HREIMS m/z 232.0749 (C
12H
10O
4, calculated value: 232.0736).
Following examples 19-22 related 6,7-dihydroxyl-cumarone (chemical formula VIII, R
10
Be hydrogen) can make by following reduction reaction, specific as follows:
In reaction flask, add 2.4 liters of methyl alcohol, 332 grams 6,7-dihydroxyl benzo furans-3 (2H)-ketone (Formula I V, R
4Be hydrogen) ,-10
oC adds sodium borohydride 250 grams in batches, after adding, slowly rises to stirring at room 15 hours.Be cooled to 0
oC slowly adds 4N HCl to PH=1.Slowly rose to room temperature reaction 5 hours.After concentrating, add 1 premium on currency and 1.2 liters of ethyl acetate, and stirred 1 hour.Tell organic layer.Organic layer is concentrated into dried after using the saturated common salt water washing.Get 264 gram solid phase prods 6,7-dihydroxyl-cumarone (chemical formula VIII, R through ethyl acetate and sherwood oil recrystallization
10Be hydrogen).Productive rate is 88%.
Embodiment 19: prepare xanthotoxol (Formulae II I, R by ring-closure reaction
3
Be hydrogen)
In reaction flask, add 20 grams 6,7-dihydroxyl-cumarone, 28 grams 3,3-diethoxy propionic acid stirs, and adds 20 milliliters of trifluoroacetic acids and 14 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 16 gram xanthotoxols through ethyl alcohol recrystallization.Productive rate is 59%.HREIMS m/z 202.0253 (C
11H
6O
4, calculated value: 202.0266).
Embodiment 20: prepare xanthotoxol (Formulae II I, R by ring-closure reaction
3
Be hydrogen)
In reaction flask, add 6,7-dihydroxyl-cumarone 50 grams, 63 grams 3,3-dimethoxy methyl propionate, stir, add 50 milliliters of trifluoroacetic acids and 35 milliliters of vitriol oils, be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature, add 700 ml waters and destroy, use 1000 milliliters of dichloromethane extractions then.Organic layer is concentrated into dried after using the saturated common salt water washing.Get 43 gram xanthotoxols through ethyl alcohol recrystallization.Productive rate is 64%.HREIMS m/z 202.0262 (C
11H
6O
4, calculated value: 202.0266).
Embodiment 21: prepare xanthotoxol (Formulae II I, R by ring-closure reaction
3
Be hydrogen)
In reaction flask, add 40 grams 6,7-dihydroxyl-cumarone, 42 gram 3-oxo propionic acid stir, and add 40 milliliters of trifluoroacetic acids and 28 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 600 ml waters and destroy, use 1 liter of dichloromethane extraction then.Organic layer is with after the saturated common salt water washing, is concentrated into driedly, gets 35 gram xanthotoxols through ethyl alcohol recrystallization.Productive rate is 65%.HREIMS m/z 202.0276 (C
11H
6O
4, calculated value: 202.0266).
Embodiment 22: prepare xanthotoxol (Formulae II I, R by ring-closure reaction
3
Be hydrogen)
In reaction flask, add 40 grams 6,7-dihydroxyl-cumarone, 50 gram 3-oxo methyl propionates stir, and add 40 milliliters of trifluoroacetic acids and 28 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 600 ml waters and destroy, use 1 liter of dichloromethane extraction then.Organic layer is with after the saturated common salt water washing, is concentrated into driedly, gets 39 gram xanthotoxols through ethyl alcohol recrystallization.Productive rate is 72%.HREIMS m/z 202.0260 (C
11H
6O
4, calculated value: 202.0266).
Embodiment 23: xanthotoxol (Formulae II I, R
3
Be hydrogen) preparation
In reaction flask, add 1 liter of methyl alcohol, 110 gram 9-hydroxyl-2H-furo [3,2-g] chromenes-3, the 7-diketone is-10
oC adds sodium borohydride 60 grams in batches, after adding, slowly rises to stirring at room 15 hours.Be cooled to 0
oC slowly adds 4N HCl to PH=1.Slowly rose to room temperature reaction 5 hours.After concentrating, add 300 ml waters and 300 milliliters of ethyl acetate, and stirred 1 hour.Tell organic layer.Organic layer is concentrated into dried after using the saturated common salt water washing.Through get 77 gram solid phase prod xanthotoxols through the ethyl alcohol recrystallization recrystallization.Productive rate is 75%.HREIMS m/z 202.0277 (C
11H
6O
4, calculated value: 202.0266).
Embodiment 24: xanthotoxol (Formulae II I, R
3
Be hydrogen) preparation
In reaction flask, add 40 gram 9-hydroxyl-2H-furo [3,2-g] chromenes-3,7-diketone, 100 gram acetic acid, 200 gram ethanol, 10 grams, 5% palladium carbon.Hydrogenation 24 hours.TLC reacts completely, and suction filtration is removed palladium carbon.Filtrate concentrates back gained solid transfer in reaction flask, adds 500 milliliter 1, the 4-dioxane.Add 125 gram dichloro dicyan para benzoquinone and 1.4 milliliter of 10% hydrochloric acid while stirring, reflux was filtered after 24 hours, and filter cake is with 50 milliliter 1, the drip washing of 4-dioxane, and filtrate is concentrated into dried.Add 500 milli ethyl acetate and 500 millis, 5% S-WAT, stir mistake after 1 hour.Filtrate is told organic layer with separating funnel.Organic layer is used saturated sodium bicarbonate and saturated common salt water washing successively, is concentrated into dried.Get 21 gram xanthotoxols through ethyl alcohol recrystallization.Productive rate is 57%.HREIMS m/z 202.0283 (C
11H
6O
4, calculated value: 202.0266).
Embodiment 25: xanthotoxol (Formulae II I, R
3
Be hydrogen) preparation
In reaction flask, add 40 gram 9-hydroxyl-2H-furo [3,2-g] chromenes-3,7-diketone, 100 gram acetic acid, 200 gram ethanol, 10 grams, 5% palladium carbon.Hydrogenation 24 hours.TLC reacts completely, and suction filtration is removed palladium carbon.Filtrate concentrates back gained solid transfer in reaction flask, adds 400 milliliters of phenyl ether, 50 grams, 5% palladium carbon.After the reflux 10 hours, be cooled to room temperature, filter.Filtrate is concentrated into dried.Get 23 gram xanthotoxols for 2 times through ethyl alcohol recrystallization.Productive rate is 62%.HREIMS m/z 202.0259 (C
11H
6O
4, calculated value: 202.0266).
6-hydroxyl-7-methoxyl group-cumarone (chemical formula VIII, R that following examples 26-29 is related
10
Be methyl) can make by following reduction reaction, concrete grammar is as follows:
In reaction flask, add 1.8 liters of methyl alcohol, 270 gram 6-hydroxyl-7-methoxyl group-cumarone-3 (2H)-ketone (Formula I V, R
4Be methyl) ,-10
oC adds sodium borohydride 188 grams in batches, after adding, slowly rises to stirring at room 15 hours.Be cooled to 0
oC slowly adds 4N HCl to PH=1.Slowly rose to room temperature reaction 5 hours.After concentrating, add 750 ml waters and 900 milliliters of ethyl acetate, and stirred 1 hour.Tell organic layer.Organic layer is concentrated into dried after using the saturated common salt water washing.Get 212 gram solid phase prod 6-hydroxyl-7-methoxyl group-cumarone (chemical formula VIII, R through ethyl acetate and sherwood oil recrystallization
10Be methyl).Productive rate is 86%.
Embodiment 26: prepare xanthotoxin (Formulae II I, R by ring-closure reaction
3
Be methyl)
In reaction flask, add 30 gram 6-hydroxyl-7-methoxyl group-cumarones, 37 grams 3,3-diethoxy propionic acid, 24 milliliters of trifluoroacetic acids and 17 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 25 gram xanthotoxins through ethyl alcohol recrystallization.Productive rate is 64%.HREIMS m/z 216.0416 (C
12H
8O
4, calculated value: 216.0423).
Embodiment 27: prepare xanthotoxin (Formulae II I, R by ring-closure reaction
3
Be methyl)
In reaction flask, add 30 gram 6-hydroxyl-7-methoxyl group-cumarones, 35 grams 3,3-dimethoxy methyl propionate, 24 milliliters of trifluoroacetic acids and 17 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature, add 400 ml waters and destroy, use 500 milliliters of dichloromethane extractions then.Organic layer is concentrated into dried after using the saturated common salt water washing.Get 24 gram xanthotoxins through ethyl alcohol recrystallization.Productive rate is 61%.HREIMS m/z 216.0413 (C
12H
8O
4, calculated value: 216.0423).
Embodiment 28: prepare xanthotoxin (Formulae II I, R by ring-closure reaction
3
Be methyl)
In reaction flask, add 25 gram 6-hydroxyl-7-methoxyl group-cumarones, 24 gram 3-oxo propionic acid, 20 milliliters of trifluoroacetic acids and 14 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 22 gram xanthotoxins through ethyl alcohol recrystallization.Productive rate is 67%.HREIMS m/z 216.0433 (C
12H
8O
4, calculated value: 216.0423).
Embodiment 29: prepare xanthotoxin (Formulae II I, R by ring-closure reaction
3
Be methyl)
In reaction flask, add 25 gram 6-hydroxyl-7-methoxyl group-cumarones, 29 gram 3-oxo methyl propionate and 23 milliliters of trifluoroacetic acids and 16 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 21 gram xanthotoxins through ethyl alcohol recrystallization.Productive rate is 64%.HREIMS m/z 216.0436 (C
12H
8O
4, calculated value: 216.0423).
Embodiment 30: xanthotoxin (Formulae II I, R
3
Be methyl) preparation
In reaction flask, add 1 liter of methyl alcohol, 116 gram 9-methoxyl group-2H-furo [3,2-g] chromenes-3, the 7-diketone is-10
oC adds sodium borohydride 60 grams in batches, after adding, slowly rises to stirring at room 15 hours.Be cooled to 0
oC slowly adds 4N HCl to PH=1.Slowly rose to room temperature reaction 5 hours.After concentrating, add 300 ml waters and 300 milliliters of ethyl acetate, and stirred 1 hour.Tell organic layer.Organic layer is concentrated into dried after using the saturated common salt water washing.Through get 86 gram solid phase prod xanthotoxins through the ethyl alcohol recrystallization recrystallization.Productive rate is 80%.HREIMS m/z 216.0415 (C
12H
8O
4, calculated value: 216.0423).
Embodiment 31: xanthotoxin (Formulae II I, R
3
Be methyl) preparation
In reaction flask, add 42 gram 9-methoxyl group-2H-furo [3,2-g] chromenes-3,7-diketone, 100 gram acetic acid, 200 gram ethanol, 10 grams, 5% palladium carbon.Hydrogenation 24 hours.TLC reacts completely, and suction filtration is removed palladium carbon.Filtrate concentrates back gained solid transfer in reaction flask, adds 500 milliliter 1, the 4-dioxane.Add 125 gram dichloro dicyan para benzoquinone and 1.4 milliliter of 10% hydrochloric acid while stirring, reflux was filtered after 24 hours, and filter cake is with 50 milliliter 1, the drip washing of 4-dioxane, and filtrate is concentrated into dried.Add 500 milli ethyl acetate and 500 millis, 5% S-WAT, stir mistake after 1 hour.Filtrate is told organic layer with separating funnel.Organic layer is used saturated sodium bicarbonate and saturated common salt water washing successively, is concentrated into dried.Get 25 gram xanthotoxins through ethyl alcohol recrystallization.Productive rate is 64%.HREIMS m/z 216.04133 (C
12H
8O
4, calculated value: 216.0423).
Embodiment 32: xanthotoxin (Formulae II I, R
3
Be methyl) preparation
In reaction flask, add 42 gram 9-methoxyl group-2H-furo [3,2-g] chromenes-3,7-diketone, 100 gram acetic acid, 200 gram ethanol, 10 grams, 5% palladium carbon.Hydrogenation 24 hours.TLC reacts completely, and suction filtration is removed palladium carbon.Filtrate concentrates back gained solid transfer in reaction flask, adds 400 milliliters of phenyl ether, 50 grams, 5% palladium carbon.After the reflux 10 hours, be cooled to room temperature, filter.Filtrate is concentrated into dried.Get 23 gram xanthotoxins for 2 times through ethyl alcohol recrystallization.Productive rate is 59%.HREIMS m/z 216.0439 (C
12H
8O
4, calculated value: 216.0423).
6-hydroxyl-7-oxyethyl group-cumarone (chemical formula VIII, R that following examples 33-34 is related
10
Be ethyl) can make by following reduction reaction, concrete grammar is as follows:
In reaction flask, add 1.9 liters of methyl alcohol, 300 gram 6-hydroxyl-7-oxyethyl group-cumarone-3 (2H)-ketone (Formula I V, R
4Be ethyl) ,-10
oC adds sodium borohydride 194 grams in batches, after adding, slowly rises to stirring at room 15 hours.Be cooled to 0
oC slowly adds 4N HCl to PH=1.Slowly rose to room temperature reaction 5 hours.After concentrating, add 750 ml waters and 900 milliliters of ethyl acetate, and stirred 1 hour.Tell organic layer.Organic layer is concentrated into dried after using the saturated common salt water washing.Get 226 gram solid phase prod 6-hydroxyl-7-oxyethyl group-cumarone (chemical formula VIII, R through ethyl acetate and sherwood oil recrystallization
10Be ethyl).Productive rate is 82%.
Embodiment 33: prepare 8-oxyethyl group-psoralene (Formulae II I, R by ring-closure reaction
3
Be ethyl)
In reaction flask, add 32 gram 6-hydroxyl-7-oxyethyl group-cumarones, 37 grams 3,3-diethoxy propionic acid, 24 milliliters of trifluoroacetic acids and 23 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 29 gram 8-oxyethyl group-psoralenes through ethyl alcohol recrystallization.Productive rate is 70%.HREIMS m/z 230.0563 (C
12H
8O
4, calculated value: 230.0579).
Embodiment 34: prepare 8-oxyethyl group-psoralene (Formulae II I, R by ring-closure reaction
3
Be ethyl)
In reaction flask, add 32 gram 6-hydroxyl-7-methoxyl group-cumarones, 29 gram 3-oxo methyl propionate and 24 milliliters of trifluoroacetic acids and 23 milliliters of vitriol oils.Be warming up to 120 degrees centigrade of reactions 4 hours, after reacting completely, reduce to room temperature.Add 300 ml waters and destroy, use 500 milliliters of dichloromethane extractions then, organic layer saturated common salt water washing.Organic layer is concentrated into dried, gets 27 gram 8-oxyethyl group-psoralenes through ethyl alcohol recrystallization.Productive rate is 65%.HREIMS m/z 230.0571 (C
12H
8O
4, calculated value: 230.0579).
Claims (6)
1. xanthotoxol derivative is characterized in that: have structure shown in chemical formula (I),
Wherein, R
1Represent hydrogen or alkyl.
2. the preparation method of the xanthotoxol derivative of a claim 1, it is characterized in that: the compound that will have a structure shown in chemical formula (IV) and compound with structure shown in chemical formula V, have any one in the compound of structure shown in chemical formula (VI) or appoint several mixtures carry out ring-closure reaction prepare as described in the xanthotoxol derivative
Wherein, R
4, R
5, R
6, R
7, R
8Represent hydrogen or alkyl independently of one another.
3. the preparation method of an xanthotoxol derivative, it is characterized in that: the compound that will have a structure shown in chemical formula (VII) and compound with structure shown in chemical formula V, have any one in the compound of structure shown in chemical formula (VI) or appoint several mixtures carry out ring-closure reaction prepare as described in the xanthotoxol derivative, described xanthotoxol derivative has structure shown in chemical formula (II)
Wherein, R
2, R
5, R
6, R
7, R
8, R
9Represent hydrogen or alkyl independently of one another.
4. the preparation method of xanthotoxol and derivative thereof, it is characterized in that: the compound that will have a structure shown in chemical formula (VIII) and compound with structure shown in chemical formula V, have shown in chemical formula (VI) any one in the structural compounds or appoint several mixtures carry out ring-closure reaction prepare as described in xanthotoxol and derivative thereof, described xanthotoxol and derivative thereof have structure shown in chemical formula (III)
Wherein, R
3, R
5, R
6, R
7, R
8, R
10Represent hydrogen or alkyl independently of one another.
5. the preparation method of xanthotoxol and derivative thereof, it is characterized in that: the compound that will have a structure shown in chemical formula (I) is earlier after xanthotoxol and derivative thereof as described in preparing behind the carbonyl reduction, dehydration, described xanthotoxol and derivative thereof have structure shown in chemical formula (III)
，
Wherein, R
1, R
3Represent hydrogen or alkyl independently of one another.
6. the preparation method of xanthotoxol and derivative thereof, it is characterized in that: the compound that will have a structure shown in chemical formula (I) earlier through hydro-reduction, again through dehydrogenation prepare as described in xanthotoxol and derivative thereof, described xanthotoxol and derivative thereof have structure shown in chemical formula (III)
Wherein, R
1, R
3Represent hydrogen or alkyl independently of one another.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110021826 CN102134247B (en) | 2011-01-19 | 2011-01-19 | Xanthotoxol derivative and new composite method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110021826 CN102134247B (en) | 2011-01-19 | 2011-01-19 | Xanthotoxol derivative and new composite method thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210388107.9A Division CN102952145B (en) | 2011-01-19 | 2011-01-19 | New synthetic method for xanthotoxol and derivatives thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102134247A true CN102134247A (en) | 2011-07-27 |
| CN102134247B CN102134247B (en) | 2013-02-06 |
Family
ID=44294193
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110021826 Expired - Fee Related CN102134247B (en) | 2011-01-19 | 2011-01-19 | Xanthotoxol derivative and new composite method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102134247B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105646414A (en) * | 2014-11-11 | 2016-06-08 | 和记黄埔医药（苏州）有限公司 | Synthetic method of 6-hydroxyl-2-methylbenzofuran type compound |
| CN107915704A (en) * | 2016-10-10 | 2018-04-17 | 北京工商大学 | A kind of synthetic method of simple coumarin kind compound |
| CN112426413A (en) * | 2020-11-13 | 2021-03-02 | 川北医学院附属医院 | Preparation method and application of xanthotoxol water-soluble nano novel dosage form |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101805350A (en) * | 2010-04-22 | 2010-08-18 | 南京大学 | Synthesis method of imperatorin derivative |
| CN102030757A (en) * | 2010-11-10 | 2011-04-27 | 武汉武药科技有限公司 | Synthesis process of methoxsalen |
-
2011
- 2011-01-19 CN CN 201110021826 patent/CN102134247B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101805350A (en) * | 2010-04-22 | 2010-08-18 | 南京大学 | Synthesis method of imperatorin derivative |
| CN102030757A (en) * | 2010-11-10 | 2011-04-27 | 武汉武药科技有限公司 | Synthesis process of methoxsalen |
Non-Patent Citations (1)
| Title |
|---|
| 《中国药物化学杂志》 20040630 王来友 等 花椒毒素的合成工艺改进 154-157 第14卷, 第3期 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105646414A (en) * | 2014-11-11 | 2016-06-08 | 和记黄埔医药（苏州）有限公司 | Synthetic method of 6-hydroxyl-2-methylbenzofuran type compound |
| CN105646414B (en) * | 2014-11-11 | 2020-05-19 | 和记黄埔医药（苏州）有限公司 | Synthesis method of 6-hydroxy-2-methylbenzofuran compound |
| CN107915704A (en) * | 2016-10-10 | 2018-04-17 | 北京工商大学 | A kind of synthetic method of simple coumarin kind compound |
| CN112426413A (en) * | 2020-11-13 | 2021-03-02 | 川北医学院附属医院 | Preparation method and application of xanthotoxol water-soluble nano novel dosage form |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102134247B (en) | 2013-02-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112209979B (en) | Production process for jointly separating high-purity glycyrrhizin, debitterized glycyrrhizin and total flavonoids from monoammonium glycyrrhizinate mother liquor | |
| CN102134247B (en) | Xanthotoxol derivative and new composite method thereof | |
| CN101928273A (en) | Method for extracting and separating isoflavone from soybeans | |
| CN106589020B (en) | A method of extracting icariin from Herba Epimedii | |
| CN102533431B (en) | Method for continuously extracting and separating sea buckthorn oil and isorhamnetin from sea buckthorn pulps | |
| CN100357358C (en) | Method for preparing licopin | |
| CN101891740A (en) | Method for extracting laburnine from upper part of thermopsis lanceolate | |
| CN101967119A (en) | Method for purifying arecoline | |
| CN102093374A (en) | Method for efficiently extracting camptothecin derivative | |
| CN101225095B (en) | Method for extracting aucubin from pedicularis plants | |
| CN1800188A (en) | Method for separating and preparing triptolide diol from tripterygium wilfordii | |
| CN102603834B (en) | Method for extracting and separating tectoridin from iris tectorum | |
| CN102432619A (en) | Preparation method of sesamin | |
| CN102952145B (en) | New synthetic method for xanthotoxol and derivatives thereof | |
| WO2007083908A1 (en) | A method for preparing decursinol from angelica gigas with high yield | |
| CN104710492A (en) | Method for extracting androstenedione in bi-liquid phases system | |
| CN100393736C (en) | Method for extracting and separating kaempoferitrin from light-leaf ligustrum sinense | |
| CN101921283B (en) | Extraction technology of gambogic acid | |
| CN102603852A (en) | Preparation method of tripterine | |
| CN101704783A (en) | Preparation method of dauricine | |
| CN102603819A (en) | Preparation method of rosavin | |
| CN102267968A (en) | Process method for preparing osthole and isopimpinellin from Cnidium | |
| CN102030814B (en) | Method for preparing high purity 9,11-dehydromanogenin | |
| CN102627540A (en) | Alnustone purification method | |
| CN102643317A (en) | Method for preparing sesaminol tri-glucoside |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130206 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |