CN103145719B - Preparation method of prodigiosin derivative - Google Patents
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- CN103145719B CN103145719B CN201310061943.0A CN201310061943A CN103145719B CN 103145719 B CN103145719 B CN 103145719B CN 201310061943 A CN201310061943 A CN 201310061943A CN 103145719 B CN103145719 B CN 103145719B
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- 0 *C(CN1)=CC1=O Chemical compound *C(CN1)=CC1=O 0.000 description 2
- FXZLAEVKFVOVMD-YVMONPNESA-N CC(CC/C=C(/C(OC)=C1)\NC1=O)O Chemical compound CC(CC/C=C(/C(OC)=C1)\NC1=O)O FXZLAEVKFVOVMD-YVMONPNESA-N 0.000 description 1
- GAEKPEKOJKCEMS-UHFFFAOYSA-N CC(CC1)OC1=O Chemical compound CC(CC1)OC1=O GAEKPEKOJKCEMS-UHFFFAOYSA-N 0.000 description 1
- IMSHXZPGTPYMGA-UHFFFAOYSA-N CC(CCC1)OC1(C(C1)OC)N=C1c1ccc[nH]1 Chemical compound CC(CCC1)OC1(C(C1)OC)N=C1c1ccc[nH]1 IMSHXZPGTPYMGA-UHFFFAOYSA-N 0.000 description 1
- KPEOFUSOGAPHSY-UHFFFAOYSA-N CC(CCC1)OC1(C(OC)=C1)NC1=O Chemical compound CC(CCC1)OC1(C(OC)=C1)NC1=O KPEOFUSOGAPHSY-UHFFFAOYSA-N 0.000 description 1
- QUXGQZCZMMKPET-SFVIPPHHSA-N CC(CCC1)O[C@]1(C(C1)OC)NC1=O Chemical compound CC(CCC1)O[C@]1(C(C1)OC)NC1=O QUXGQZCZMMKPET-SFVIPPHHSA-N 0.000 description 1
- TXKQBYYDTLOLHA-UHFFFAOYSA-N COC(CN1)=CC1=O Chemical compound COC(CN1)=CC1=O TXKQBYYDTLOLHA-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention discloses a preparation method of prodigiosin derivative. The structural formula of the prodigiosin derivative compound is shown in a formula I. The preparation method comprises the following steps of: 1) in the presence of alkali, reacting a compound shown in a formula 2 and a compound shown as a formula 4; 2) carrying out a cyclization reaction on the obtained products in the presence of an acid catalyst; 3) carrying out a reduction reaction on the obtained products; and 4) carrying out a Weisimaisi reaction between the obtained products and a compound shown in a formula 7 to obtain a compound shown in a formula 1. The preparation method disclosed by the invention has the advantages of simple steps, mild reaction conditions and high yield, is easy to enlarge and convenient for products derivatization and has great industrial production potential.The invention discloses a preparation method of prodigiosin derivative. The structural formula of the prodigiosin derivative compound is shown as a formula I. The preparation method comprises the following steps of: 1) in the presence of alkali, reacting a compound shown as a formula 2 and a compound shown as a formula 4; 2) carrying out a cyclization reaction on the obtained products in the presence of an acid catalyst; 3) carrying out a reduction reaction on the obtained products; and 4) carrying out a Weisimaisi reaction between the obtained products and a compound shown as a formula 7 to obtain a compound shown as a formula 1. The preparation method disclosed by the invention has the advantages of simple steps, mild reaction conditions and high yield, is easy to enlarge and convenient for products derivatization and has great industrial production potential.
Description
Technical field
The present invention relates to a kind of preparation method of prodigiosin derivative.
Background technology
2008, Fenical research group extracts prodigiosin derivative (1) (2) (Marineosins A and B) (Org.Lett.2008 that a class has brand-new carbon skeleton from a kind of actinomycetes settling (Streptomyces) of marine streptomyces, 10,5505-5508).The biological activity test of this alkaloid compound is shown: 1 and 2 demonstrate good biological activity (IC for colon cancer cell (HCT-116)
50=0.5 μM and IC
50=46 μMs), also have melanoma and leukaemia cancer cell in addition and select inhibit activities very well, so be expected to the lead compound of the anticancer clinical medicine for development of new to its research transformation.
Compound 1 and 2 derives from actinomycetic metabolic derivative, but adopts these class methods to carry out extracting the restriction that this compounds is subject to the features such as productive rate is low, product is single.Utilize the mode of chemosynthesis, this compounds can not only be prepared in a large number, and, the derivative of this compounds can be prepared, set up compound library, be convenient to the research carrying out the aspect such as related biological and pharmacy.
Summary of the invention
The object of this invention is to provide a kind of preparation method of prodigiosin derivative.
The structural formula of prodigiosin derivative of the present invention is such as formula shown in I:
(formula I)
In formula I, R
1and R
2all be selected from following radicals any one: hydrogen atom, C
1-C
12alkyl, C
1-C
12alkoxy methyl, C
1-C
12alkoxyethyl, C
3-C
12aryl, benzyl, to methoxy-benzyl, C
1-C
12carbalkoxy, C
1-C
12acyl group, trimethyl silicon based, triethyl is silica-based, t-Butyldimethylsilyl, tert-butyl diphenyl are silica-based, triisopropylsilyl, triphenyl are silica-based and C
1-C
12alkylsulfonyl;
R
3be selected from following radicals any one: C
1-C
12alkyl, C
1-C
12alkoxy methyl, C
1-C
12alkoxyethyl, C
3-C
12aryl, benzyl, to methoxy-benzyl, C
1-C
12carbalkoxy, C
1-C
12acyl group, trimethyl silicon based, triethyl is silica-based, t-Butyldimethylsilyl, tert-butyl diphenyl are silica-based, triisopropylsilyl, triphenyl are silica-based and C
1-C
12alkylsulfonyl;
R
4be selected from following radicals any one: the disubstituted amino of the amino (NHR ') of hydrogen atom, halogen atom, hydroxyl, OR ', amino, the monosubstituted base of band R ' group, band R ' group (NR '
2), sulfydryl, SR ', cyano group, carboxyl, C
1-C
12carbalkoxy, by R " group replace C
1-C
12carbalkoxy, C
1-C
12acyl group, by R " group replace C
1-C
12acyl group, C
1-C
12alkyl, by R " group replace C
1-C
12alkyl, C
3-C
12cycloalkyl, C
3-C
12heterocyclic radical, C
3-C
12aryl, by R " group replace C
3-C
12aryl, C
3-C
12heteroaryl, by R " group replace C
3-C
12heteroaryl, C
1-C
12alkylsulfonyl, C
2-C
12thiazolinyl and C
2-C
12alkynyl;
Wherein, described R ' group is selected from any one group following: C
1-C
12carbalkoxy, C
1-C
12acyl group, trifluoromethyl, C
1-C
12alkyl, benzyl, to methoxy-benzyl, C
3-C
12aryl, C
1-C
12alkylsulfonyl, C
1-C
12alkoxy methyl and C
1-C
12alkoxyethyl;
" group is selected from any one group following to described R: halogen atom, hydroxyl, C
1-C
12alkoxyl group, amino, C
1-C
12alkyl amine group, C
1-C
12two alkyl amine group, C
1-C
12arylamine group, C
3-C
12heterocyclic radical, C
3-C
12aryl, C
3-C
12heteroaryl, sulfydryl, C
1-C
12alkane sulfydryl and C
1-C
12alkyl.
The method of prodigiosin derivative shown in preparation formula I, comprises the steps:
1) in the presence of a base, compound shown in compound and formula III shown in formula II is reacted, obtains compound shown in formula IV;
(formula II) (formula III) (formula IV)
In formula II, R
1, R
2all be selected from following radicals any one: hydrogen atom, C
1-C
12alkyl, C
1-C
12alkoxy methyl, C
1-C
12alkoxyethyl, C
3-C
12aryl, benzyl, to methoxy-benzyl, C
1-C
12carbalkoxy, C
1-C
12acyl group, trimethyl silicon based, triethyl is silica-based, t-Butyldimethylsilyl, tert-butyl diphenyl are silica-based, triisopropylsilyl, triphenyl are silica-based and C
1-C
12alkylsulfonyl; R
5be selected from any one group following: amino, sulfydryl, SR ', cyano group, carboxyl, C that the amino of hydrogen atom, halogen atom, hydroxyl, OR ', amino, the monosubstituted base of band R ' group, band R ' group are disubstituted
1-C
12carbalkoxy, by R " group replace C
1-C
12carbalkoxy, C
1-C
12acyl group, by R " group replace C
1-C
12acyl group, C
1-C
12alkyl, by R " group replace C
1-C
12alkyl, C
3-C
12cycloalkyl, C
1-C
12heterocyclic radical, C
3-C
12aryl, by R " group replace C
3-C
12aryl, C
3-C
12heteroaryl, by R " group replace C
3-C
12heteroaryl, C
1-C
12alkylsulfonyl, C
2-C
12thiazolinyl and C
2-C
12alkynyl;
R in formula III
3be selected from following radicals any one: amino, sulfydryl, SR ', cyano group, carboxyl, C that the amino of halogen atom, hydroxyl, OR ', amino, the monosubstituted base of band R ' group, band R ' group are disubstituted
1-C
12carbalkoxy, by R " group replace C
1-C
12carbalkoxy, C
1-C
12acyl group, by R " group replace C
1-C
12acyl group, C
1-C
12alkyl, by R " group replace C
1-C
12alkyl, C
3-C
12cycloalkyl, C
1-C
12heterocyclic radical, C
3-C
12aryl, by R " group replace C
3-C
12aryl, C
3-C
12heteroaryl, by R " group replace C
3-C
12heteroaryl, C
1-C
12alkylsulfonyl, C
2-C
12thiazolinyl and C
2-C
12alkynyl;
R in formula IV
1, R
2definition cotype II, R
3the same formula III of definition;
2) compound shown in formula IV carries out cyclization in presence of an acid catalyst, obtains compound shown in formula V;
(formula V)
In formula V, R
1, R
2, R
3definition cotype IV;
3) compound shown in formula V carries out hydro-reduction reaction under reductive agent effect, obtains the compound shown in formula VI;
(formula VI)
In formula VI, R
1, R
2, R
3definition cotype V;
4) compound shown in compound and formula VII shown in formula VI is carried out Vilsmeier-Haack reaction under the effect of reagent, obtain compound shown in formula I;
(formula I) (formula VII)
R in formula VII
4be selected from any one group following: amino, sulfydryl, SR ', cyano group, carboxyl, C that the amino of hydrogen atom, halogen atom, hydroxyl, OR ', amino, the monosubstituted base of band R ' group, band R ' group are disubstituted
1-C
12carbalkoxy, by R " group replace C
1-C
12carbalkoxy, C
1-C
12acyl group, by R " group replace C
1-C
12acyl group, C
1-C
12alkyl, by R " group replace C
1-C
12alkyl, C
3-C
12cycloalkyl, C
1-C
12heterocyclic radical, C
3-C
12aryl, by R " group replace C
3-C
12aryl, C
3-C
12heteroaryl, by R " group replace C
3-C
12heteroaryl, C
1-C
12alkylsulfonyl, C
2-C
12thiazolinyl and C
2-C
12alkynyl;
Wherein, described R ' group is selected from any one group following: C
1-C
12carbalkoxy, C
1-C
12acyl group, trifluoromethyl, C
1-C
12alkyl, benzyl, to methoxy-benzyl, C
3-C
12aryl, C
1-C
12alkylsulfonyl, C
1-C
12alkoxy methyl and C
1-C
12alkoxyethyl;
" group is selected from any one group following to described R: halogen atom, hydroxyl, C
1-C
12alkoxyl group, amino, C
1-C
12alkyl amine group, C
1-C
12two alkyl amine group, C
1-C
12arylamine group, C
3-C
12heterocyclic radical, C
3-C
12aryl, C
3-C
12heteroaryl, sulfydryl, C
1-C
12alkane sulfydryl and C
1-C
12alkyl.
Aforesaid method, step 1) described in alkali formula III can be made to remove hydrogen evolution negative ion carry out Aldol reaction.Described alkali specifically can be mineral alkali, as sodium hydroxide.Described temperature of reaction can be 0 DEG C-100 DEG C, specifically can be 55 DEG C; The time of described reaction can be 1 hour-168 hours, and the concrete time is 12 hours; Shown in described formula III, shown in compound, formula II, the mol ratio of compound can be (0.5-10): 1.0, specifically can be 1.1: 1.0.
Aforesaid method, step 2) described in acid catalyst can be a hydration tosic acid, tosic acid, methylsulfonic acid, camphorsulfonic acid or trifluoromethanesulfonic acid; Described temperature of reaction can be 0 DEG C-100 DEG C, specifically can be 60 DEG C; The time of described reaction can be 0.5 hour-72 hours, and the concrete time can be 24 hours; Shown in described acid catalyst, formula IV, the mol ratio of compound can be (0.05-1.0): 1.0, specifically can be 0.2: 1.
Aforesaid method, step 3) described in reductive agent can be palladium carbon, Wilkinson catalyst or platinum oxide; Described temperature of reaction can be 0 DEG C-100 DEG C, specifically can be 60 DEG C; The pressure of hydrogen can be 1-100atm, specifically can be 50atm; The time of described reaction can be 0.5 hour-72 hours, and the concrete time can be 24 hours; Shown in described reductive agent and formula V, the mol ratio of compound can be (0.05-1.0): 1.0, specifically can be 0.2: 1.
Aforesaid method, step 4) described in reagent can be phosphorus oxychloride, tribromo oxygen phosphorus, oxalyl chloride or trifluoromethanesulfanhydride anhydride; Described temperature of reaction can be-20 DEG C-100 DEG C, specifically can be 25 DEG C; The time of described reaction can be 0.1 hour-50 hours, and the concrete time can be 3 hours; Shown in described reagent and formula VI, the mol ratio of compound can be (1-10): 1.0, specifically can be 2.0: 1.0.
In aforesaid method, step 1), step 2), step 3) with step 4) solvent of described reaction all can be selected from least one in following solvents: water, methylene dichloride, chloroform, methyl alcohol, ethanol, the trimethyl carbinol, tetrahydrofuran (THF), DMF, acetic acid and acetonitrile.
Compound provided by the invention be structure of modification carries out to alkaloid compound (Marineosins) basis on obtain, it is expected to the lead compound for novel anticancer clinical medicine.This compounds process for production thereof step is simple and direct, and cost of material is cheap, and reaction conditions is gentle, and productive rate is higher, simple to operate, is convenient to amplify, is convenient to derive product, has larger industrial potentiality.
Embodiment
Below by specific embodiment, method of the present invention is described, but the present invention is not limited thereto.
Experimental technique described in following embodiment, if no special instructions, is ordinary method; Described reagent and material, if no special instructions, all can obtain from commercial channels.
Compound (R shown in formula II used in following embodiment
1=R
2=H) according to the method preparation comprised the steps:
(formula VIII) (formula II-a)
Under nitrogen protection; 7.51g γ-valerolactone (formula VIII) is added in flask; add 200mL anhydrous methylene chloride to dissolve; be cooled to-78 DEG C; be that the diisobutyl aluminium hydride solution 69.2mL of 1.3M was injected in flask with 2 hours with syringe pump being dissolved in concentration in normal hexane, then this thermotonus 1 hour.Add 20mL methyl alcohol cancellation reaction, then add the saturated potassium sodium tartrate solution of 200mL, stirring at room temperature 2 hours.Use diatomite filtration.Methylene dichloride (300mL x3) extracts, and merges organic phase.Wash with saturated aqueous common salt (100mLx3).Concentrate and obtain compound shown in 6.92g pale yellow oily liquid body (90%) formula II-a.Not needing purifies further is directly used in next step reaction.
The preparation of embodiment 1, prodigiosin derivative
The structural formula of prepared prodigiosin derivative is such as formula shown in I-a.
(formula IV-a) (formula III-a) (formula V-a)
(formula VI-a) (formula VII-a) (formula I-a)
By compound dissolution shown in 8.40g formula III-a in the sodium hydroxide solution of 110mL4N, be heated to 55 DEG C.Compound shown in 6.90g formula II-a is dissolved in 110mL methyl alcohol, then this solution is added dropwise in above-mentioned sodium hydroxide solution, make it after adding 55 DEG C of reactions 12 hours.Be cooled to room temperature, concentrate and organic solvent is removed, be then placed on (0 DEG C) in refrigerator and place 24 hours, separate out white solid.Filtration washes with water and namely obtains the 7.28g of compound shown in formula IV-a, white solid (55%).
Structural identification result is as follows: mp.84-86 DEG C, IR (film): 3355,1664,1598cm
-1;
1h NMR (CDCl
3, 400MHz) and δ 9.64 (s, 1H), 5.52 (t, J=8.8Hz, 1H), 5.11 (s, 1H), 3.81 (s, 3H), 3.84-3.73 (m, 1H), 3.47 (s, 1H), 2.46-2.30 (m, 2H), 1.65-1.53 (m, 2H), 1.18 (d, J=6.4Hz, 3H);
13c NMR (100MHz, CDCl
3) δ 173.3,166.5,134.2,111.5,92.9,66.7,58.2,38.5,23.8,23.4; HRMSCalcd for C
10h
15nO
3(M
+): 197.1052; Found:197.1054.
Compound shown in 0.197g formula IV-a and 0.038g mono-hydration tosic acid are dissolved in 16mL chloroform, are then heated to 60 DEG C of reactions 24 hours.Be cooled to room temperature, add 0.5mL triethylamine cancellation reaction.Concentrated except desolventizing, excessively flash column purifiedly obtain compound shown in 0.106g formula V-a (54%), white solid.
Structural identification result is as follows: mp.177-180 DEG C; IR (film): 3232,1676,1597cm
-1;
1h NMR (400MHz, CDCl
3) δ 7.70 (br, 1H), 4.96 (s, 1H), (3.85 s, 3H), 3.83-3.74 (m, 1H), 2.04-1.87 (m, 2H), (1.83-1.66 m, 2H), 1.60-1.53 (m, 1H), 1.40-1.28 (m, 1H), (1.21 d, J=6.0Hz, 3H);
13cNMR (100MHz, CDCl
3) δ 176.8,174.0,92.6,88.3,70.7,58.8,32.1,30.9,22.2,20.0; HRMSCalcd for C
10h
15nO
3(M
+): 197.1052; Found:197.1055.
Compound shown in 0.099g formula V-a and 0.02g10% palladium carbon (adding 50% water moistening) are dissolved in 3mL methyl alcohol, be filled with the hydrogen of 50atm, then 60 DEG C of reactions 24 hours are heated to, be cooled to room temperature, with alumina filter, concentrated removing methyl alcohol, excessively flash column purifiedly obtains compound shown in 0.271g formula VI-a (27%), white solid.
Structural identification result is as follows: mp.146-149 DEG C; IR (film): 3351,3183,1710cm
-1;
1h NMR (CDCl
3, 400MHz) and δ 7.69 (br, 1H), 3.71-3.61 (m, 2H), 3.36 (s, 3H), 2.74 (dd, J=17.2,5.6Hz, 1H), 2.30 (dd, J=17.2,2.0Hz, 1H), 1.89-1.80 (m, 2H), 1.73-1.51 (m, 3H), 1.31-1.19 (m, 1H), 1.12 (d, J=6.4Hz, 3H);
13c NMR (100MHz, CDCl
3) δ 177.5,92.5,84.0,68.0,57.7,36.1,32.9,29.1,22.2,19.8; HRMS Calcd for C10H17NO3 (M
+): 199.1208; Found:199.1211.
Under condition of nitrogen gas, compound shown in 0.02g formula VI-a is dissolved in compound shown in 1mL formula VII-a, is placed in 0 DEG C of reactive bath technique, after being added dropwise to 0.0336mL trifluoromethanesulfanhydride anhydride, move to room temperature reaction 3 hours.Add 1mL sodium hydroxide (1N) solution cancellation reaction, methylene dichloride (5mL x3) extracts, and merges organic phase, anhydrous magnesium sulfate drying, filters, concentrated, cross and flash column purifiedly obtain compound shown in 0.0226g formula I-a (91%), faint yellow solid.
Structural identification result is as follows: mp.68-70 DEG C, IR (fi1m): 3133,1606cm
-1,
1h NMR (CDCl
3, 400MHz) δ 6.89 (dd, J=2.4, 1.2Hz, 1H), 6.55 (dd, J=3.6, 1.6Hz, 1H), 6.21 (dd, J=3.6, 2.8Hz, 1H), 4.27-4.18 (m, 1H), 3.83 (dd, J=7.2, 6.4Hz, 1H), 3.44 (s, 3H), 3.20 (dd, J=16.4, 6.8Hz, 1H), 2.74 (dd, J=16.4, 5.6Hz, 1H), 2.07-1.92 (m, 1H), 1.83-1.68 (m, 2H), 1.68-1.60 (m, 1H), 1.60-1.52 (m, 1H), 1.38-1.23 (m, 1H), 1.10 (d, J=6.4Hz, 3H),
13cNMR (100MHz, CDCl
3) δ 163.4,128.0,122.5,113.9,109.9,103.7,87.2,68.7,58.3,38.8,33.7,29.0,22.6,20.0, HRMS Calcdfor C
14h
20n
2o
2(M
+): 248.1525, Found:248.1528.
Through Structural Identification, gained compound is really target compounds of formula I-a.
Claims (5)
1. the method for prodigiosin derivative shown in preparation formula I,
In formula I, R
1, R
2be hydrogen atom; R
3for methyl; R
4for hydrogen atom;
Comprise the steps:
1) in the presence of a base, compound shown in compound and formula III shown in formula II is reacted, obtains compound shown in formula IV;
Wherein, in described formula II, R
1, R
2definition cotype I, R in described formula III
3definition cotype I; In described formula IV, R
1, R
2definition cotype II, R in described formula III, formula IV
3definition cotype III;
2) make compound shown in described formula IV carry out cyclization in presence of an acid catalyst, obtain compound shown in formula V;
In formula V, R
1, R
2, R
3definition cotype IV;
3) make compound shown in described formula V carry out hydro-reduction reaction under reductive agent effect, obtain the compound shown in formula VI;
In formula VI, R
1, R
2, R
3definition cotype V;
4) compound shown in compound and formula VII shown in described formula VI is carried out Vilsmeier-Haack reaction under the effect of reagent, obtain compound shown in described formula I;
R in formula VII
4definition cotype I;
Described step 1) in, described alkali is mineral alkali; Described temperature of reaction is 0 DEG C-100 DEG C; The time of described reaction is 1 hour-168 hours; Shown in described formula III, shown in compound, formula II, the mol ratio of compound is 0.5-10:1.0;
Described step 2) in, described acid catalyst is selected from following at least one: a hydration tosic acid, tosic acid, methylsulfonic acid, camphorsulfonic acid and trifluoromethanesulfonic acid; Described temperature of reaction is 0 DEG C-100 DEG C; The time of described reaction is 0.5 hour-72 hours; Shown in described acid catalyst, formula IV, the mol ratio of compound is 0.05-1.0:1.0;
Described step 3) described in reductive agent be palladium carbon, Wilkinson catalyst or platinum oxide; Described temperature of reaction is 0 DEG C-100 DEG C; The pressure of described hydrogen in reaction is 1-100atm; The time of described reaction is 0.5 hour-72 hours; The mol ratio of compound shown in described reductive agent and formula V is 0.05-1.0:1.0;
Described step 4) described in reagent be phosphorus oxychloride, tribromo oxygen phosphorus, oxalyl chloride or trifluoromethanesulfanhydride anhydride; Described temperature of reaction is-20 DEG C-100 DEG C; The time of described reaction is 0.1 hour-50 hours; The mol ratio of compound shown in described reagent and formula VI is 1-10:1.0;
Described step 1), step 2), step 3) with step 4) described in the reaction solvent that reacts all be selected from least one in following solvents: water, methylene dichloride, chloroform, methyl alcohol, ethanol, the trimethyl carbinol, tetrahydrofuran (THF), DMF, acetic acid and acetonitrile.
2. method according to claim 1, is characterized in that: described step 1) in, described mineral alkali is sodium hydroxide; Described temperature of reaction is 55 DEG C; The time of described reaction is 12 hours; Shown in described formula III, shown in compound, formula II, the mol ratio of compound is 1.1:1.0.
3. method according to claim 1, is characterized in that: described step 2) in; Described temperature of reaction is 60 DEG C; The time of described reaction is 24 hours; Shown in described acid catalyst, formula IV, the mol ratio of compound is 0.2:1.
4. method according to claim 1, is characterized in that: described step 3) in, described temperature of reaction is 60 DEG C; The pressure of described hydrogen in reaction is 50atm; The time of described reaction is 24 hours; The mol ratio of compound shown in described reductive agent and formula V is 0.2:1.
5. method according to claim 1, is characterized in that: described step 4) in, described temperature of reaction is 25 DEG C; The time of described reaction is 3 hours; The mol ratio of compound shown in described reagent and formula VI is 2.0:1.0.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001055131A2 (en) * | 2000-01-26 | 2001-08-02 | Gemin X Biotechnologies Inc. | Prodigiosin-derivatives as neoplastic and anti-viral agents |
| CN102731484A (en) * | 2012-06-19 | 2012-10-17 | 安徽师范大学 | Preparation method for prodigiosins analogue |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001055131A2 (en) * | 2000-01-26 | 2001-08-02 | Gemin X Biotechnologies Inc. | Prodigiosin-derivatives as neoplastic and anti-viral agents |
| CN102731484A (en) * | 2012-06-19 | 2012-10-17 | 安徽师范大学 | Preparation method for prodigiosins analogue |
Non-Patent Citations (2)
| Title |
|---|
| Marineosins A and B, Cytotoxic Spiroaminals from a Marine-Derived Actinomycete;Chollaratt Boonlarppradab，等;《Org. Lett.》;20081113;第10卷(第24期);第5505-5508页 * |
| 灵菌红素的研究进展;刘同军等;《食品与药品》;20070810;第9卷(第08期);第47-51页 * |
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