CN114524815B - 8-alkoxypurine derivative and preparation method and application thereof - Google Patents

Abstract

The invention discloses an 8-alkoxyl purine derivative, a preparation method and application thereof, wherein the structure of the 8-alkoxyl purine derivative is shown as a formula (I):

Description

8-alkoxypurine derivative and preparation method and application thereof

Technical Field

The invention belongs to the field of organic chemistry, and particularly relates to an 8-alkoxypurine derivative, and a preparation method and application thereof.

Background

8-alkoxypurines are the main components of many natural nucleoside compounds, higher pharmaceutical intermediates, and biologically active substances, which generally have highly potent antitumor and antiviral physiological activities, as well as excellent antibacterial ability. In view of the above pharmacological properties, it is of great value to develop an efficient green synthesis method for 8-alkoxypurines.

The currently known synthesis methods of 8-alkoxypurine compounds mainly comprise: 1. directly synthesizing 8-alkoxypurine compounds by using sodium methoxide and methanol by using purine compounds as substrates; 2. brominating the 8-position of the purine by using NBS, and then synthesizing the 8-alkoxypurine compound by using NaH and alcohol; 3. alkylation at the purine C-8 position is achieved by copper-catalyzed intramolecular dehydrocoupling of purine nucleosides. Among the three methods, the first method has lower yield (about 25 percent), harsh reaction conditions and severely limited substrate range, and can only be applied to reaction systems of methanol/sodium methoxide and ethanol/sodium ethoxide; the second method has complex reaction route, needs multi-step reaction, has high process cost and severely reduces the yield of the whole reaction; the third method can only be applied to intramolecular ring closure synthesis, and needs transition metal copper as a catalyst, the copper catalyst is easy to chelate or coordinate with purine so as to influence the yield, the reaction also needs heating, and the preparation process does not accord with the concept of green environmental protection. The preparation of 8-alkoxypurine compounds has been widely studied at home and abroad, but the disclosed preparation method has the problems of small substrate application range, heating under reaction conditions, transition metal as catalyst and low product yield, so that it is necessary to develop a synthesis method of 8-alkoxypurine compounds with wide substrate application range, mild reaction conditions, no transition metal and high product yield.

Disclosure of Invention

In order to overcome the problems of the prior art described above, it is an object of the present invention to provide an 8-alkoxypurine derivative; it is a second object of the present invention to provide a process for producing such an 8-alkoxypurine derivative; it is a further object of the present invention to provide the use of such 8-alkoxypurine derivatives.

In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:

in a first aspect, the present invention provides an 8-alkoxypurine derivative, wherein the structure of the 8-alkoxypurine derivative is shown as formula (I):

in the formula (I), R ¹ Selected from substituted or unsubstituted alkoxy groups; r is R ² Selected from substituted or unsubstituted alkyl, alkoxycarbonylalkyl; r is R ³ Selected from the group consisting of substituted or unsubstituted alkyl groups, substituted or unsubstituted alkoxyalkyl groups.

Preferably, in formula (I), R ¹ Alkoxy selected from C1-C4; r is R ² Selected from C1-C4 alkyl, C1-C4 alkoxycarbonylalkyl, substituted or unsubstituted benzyl; r is R ³ Selected from C1-C16 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxyalkyl; further preferred, in formula (I), R ¹ Selected from methoxy; r is R ² Selected from methyl, ethyl, ethoxycarbonylmethyl, benzyl, methyl substituted benzyl; r is R ³ Selected from methyl, ethyl, isopropyl, butyl, n-dodecyl, cyclohexyl, hydroxyethyl, methoxyethyl.

Preferably, the 8-alkoxypurine derivative comprises a compound having the structure shown below:

according to a second aspect of the present invention there is provided a process for the preparation of an 8-alkoxypurine derivative according to the first aspect of the present invention comprising the steps of:

mixing 8H-purine derivatives with alcohol, a photocatalyst, an oxidant, carboxylic acid or derivatives thereof, and reacting under the illumination condition to obtain the 8-alkoxypurine derivatives;

the structure of the 8H-purine derivative is shown as a formula (II);

in the formula (II), R ⁴ Selected from substituted or unsubstituted alkoxy groups; r is R ⁵ Selected from substituted or unsubstituted alkyl, alkoxycarbonylalkyl;

the alcohol is in excess relative to the 8H-purine derivative.

Preferably, in formula (II), R ⁴ Alkoxy selected from C1-C4; r is R ⁵ Selected from C1-C4 alkyl, C1-C4 alkoxycarbonylalkyl, substituted or unsubstituted benzyl; further preferred, in formula (II), R ⁴ Selected from methoxy; r is R ⁵ Selected from methyl, ethyl, ethoxycarbonylmethyl, benzyl, methyl substituted benzyl.

Preferably, the alcohol comprises at least one of C1-C16 alkyl alcohol, C1-C4 alkyl glycol, and C1-C4 alkoxy alcohol; further preferably, the alcohol comprises at least one of methanol, ethanol, isopropanol, butanol, n-dodecanol, cyclohexanol, ethylene glycol monomethyl ether.

Preferably, the molar ratio of the 8H-purine derivative to the alcohol is 1: (2-50); further preferably, the molar ratio of the 8H-purine derivative to alcohol is 1: (2-40).

Preferably, the molar ratio of the 8H-purine derivative to the photocatalyst, oxidant, carboxylic acid or derivative thereof is 1: (0.02-0.06): (1-3): (1-6); further preferably, the molar ratio of the 8H-purine derivative to the photocatalyst, oxidant, carboxylic acid or derivative thereof is 1: (0.03-0.05): (1-3): (2-5).

Preferably, the photocatalyst comprises at least one of an acridine salt photocatalyst and a pyrylium salt photocatalyst; further preferably, the photocatalyst comprises 10-methyl-9-mesityl acridine perchlorate (Acr ⁺ –Mes ClO ₄ ^- ) At least one of 2,4, 6-triphenylpyrylium tetrafluoroborate (TPT).

Preferably, the wavelength of the illumination light is 450nm-480nm; further preferably, the wavelength of the illumination light is 450nm to 465nm.

Preferably, the carboxylic acid or derivative thereof comprises at least one of trifluoroacetic acid, acetic acid, propionic acid, butyric acid, levulinic acid, pivalic acid; further preferably, the carboxylic acid or derivative thereof comprises at least one of trifluoroacetic acid, acetic acid, pivalic acid.

Preferably, the oxidizing agent comprises at least one of air, oxygen, di-t-butyl peroxide (DTBP), t-butyl hydroperoxide (TBHP); further preferably, the oxidizing agent comprises at least one of air, oxygen, tert-butyl hydroperoxide (TBHP); still further preferably, the oxidizing agent includes at least one of air and oxygen.

Preferably, the solvent for the reaction comprises at least one of nitrile solvent and halogenated hydrocarbon solvent; further preferably, the solvent for the reaction comprises at least one of acetonitrile, dichloromethane, dichloroethane.

Preferably, the temperature of the reaction is 15-40 ℃; further preferably, the temperature of the reaction is 15 ℃ to 25 ℃.

Preferably, the reaction time is 8h-36h; further preferably, the reaction time is 12h to 24h.

In a third aspect, the invention provides the use of the 8-alkoxypurine derivative according to the first aspect of the invention in the manufacture of an anti-tumour, antiviral or antibacterial agent.

The beneficial effects of the invention are as follows:

the 8-alkoxyl purine derivative provided by the invention has a novel structure and various compound types; the preparation method of the compound does not need a metal catalyst to participate in the reaction, the catalyst and the raw materials are cheap and easy to obtain, the reaction condition is mild, the reaction steps are few, the operation is simple, the visible light can be catalyzed, the optional range of the alcohol reagent is wide, and various required 8-alkoxyl purine derivatives can be synthesized; the 8-alkoxypurine derivative can be applied to the preparation of antitumor drugs, antiviral drugs or antibacterial drugs.

In particular, the invention has the following advantages:

1. the 8-alkoxyl purine derivative provided by the invention has a novel structure, various compounds and the structure of the prepared compound is confirmed through a nuclear magnetic resonance hydrogen spectrogram, a nuclear magnetic resonance carbon spectrogram and a high-resolution mass spectrogram, and the 8-alkoxyl purine derivative enriches a chemical molecular library.

2. The green efficient synthesis method of the 8-alkoxypurine derivative provided by the invention can be used for dehydrogenating, oxidizing and coupling purine and alcohol to obtain the 8-alkoxypurine derivative in one step under the condition of no alkali or metal catalysis, so that the atomic economy and the process economy of the synthesis of the compound are realized; the catalyst used in the preparation method is cheap and easy to obtain, and the catalyst used in the preparation method is a nonmetallic photocatalyst, so that the expensive transition metal photocatalyst is avoided, the catalysis effect is good, and meanwhile, the problem that the transition metal catalyst is poisoned by nitrogen atoms on purine rings is also avoided; the invention solves the problems of expensive raw materials, complex process, harsh reaction conditions and the like in the process of preparing the 8-alkoxyl purine derivative; the synthetic route provided by the invention is only to add a photocatalyst, carboxylic acid or a derivative thereof and an oxidant into raw materials, and react under the air condition under the visible light with the wavelength of 450-480 nm, so that the harsh conditions of no water and no oxygen are avoided; the alcohol compounds used in the invention are cheap and easy to obtain, and the sources of raw materials are wide; the preparation method provided by the invention modifies and reforms the purine ring through photocatalysis, and the 8-alkoxyl purine derivative with good biological activity is synthesized in a green and efficient way under mild conditions.

3. The 8-alkoxypurine derivative provided by the invention can be applied to preparation of antitumor drugs, antiviral drugs or antibacterial drugs, provides a diversified purine molecule library for research of antitumor, antiviral and antibacterial drugs, and has a wide industrial application prospect.

Drawings

FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of Compound 1.

FIG. 2 is a nuclear magnetic resonance carbon spectrum of Compound 1.

Detailed Description

The following examples are presented to further illustrate the practice of the invention, but are not intended to limit the practice and protection of the invention. It should be noted that the following processes, if not specifically described in detail, can be realized or understood by those skilled in the art with reference to the prior art. The reagents or instruments used did not identify the manufacturer and were considered conventional products available commercially.

The following examples develop a new synthetic route for 8-alkoxypurine derivatives by dehydrogenation oxidative coupling reaction using inexpensive and readily available alcohol compounds as raw materials and adding a photocatalyst, a solvent, an oxidant and carboxylic acid or derivatives thereof, and the specific synthetic reaction formula of the 8-alkoxypurine derivatives in the examples is as follows:

example 1

The specific preparation steps of the compound 1 are as follows:

a10 ml tube was sealed with a dry magnet added thereto, 9-benzyl-6-methoxy-9H-purine (0.1 mmol,0.0241 g), methanol (1 mmol,0.0320 g) and Acr were added ⁺ –Mes ClO ₄ ^- (3 mol%,0.0012 g), TFA (0.2 mmol,0.0228 g), and 2mL MeCN solvent. The reaction tube was placed in a 20W LED (450 nm to 465 nm) under air conditions and irradiated at room temperature for 18 hours. The reaction was followed by TLC, after the termination of the reaction, the solvent was concentrated in vacuo and the target product 9-benzyl-6, 8-dimethoxy-9H-purine (designated Compound 1) was obtained by column chromatography purification in 93% yield. The nuclear magnetic hydrogen spectrum, carbon spectrum and high resolution mass spectrum data of compound 1 are as follows: ¹ H NMR(400MHz，CDCl ₃ )δ8.45(s，1H)，7.36–7.23(m，5H)，5.23(s，2H)，4.22(s，3H)，4.15(s，3H). ¹³ C NMR(101MHz，CDCl ₃ )δ158.34，156.69，152.14，150.34，135.75，128.77，128.04，127.79，117.73，57.54，53.98，44.92；HR-MS(ESI)calcd for C ₁₄ H ₁₅ N ₄ O ₂ ，[M+H] ⁺ :271.1195, found:271.1195. fig. 1 is a nuclear magnetic resonance hydrogen spectrum of the compound 1, and fig. 2 is a nuclear magnetic resonance carbon spectrum of the compound 1.

The structure of compound 1 is shown below:

example 2

The specific preparation steps of compound 2 are as follows:

a10 ml tube was sealed with a dry magnet and 6-methoxy-9- (3-methylbenzyl) -9H purine (0.1 mmol,0.0254 g), methanol (1 mmol,0.0320 g) and Acr were added ⁺ –Mes ClO ₄ ^- (3 mol%,0.0012 g), TFA (0.2 mmol,0.0228 g), and 2mL MeCN solvent. The reaction tube was placed in a 20W LED (450 nm to 465 nm) under air conditions and irradiated at room temperature for reaction for 12 hours. The reaction was followed by TLC, after the termination of the reaction, the solvent was concentrated in vacuo and the target product 6, 8-dimethoxy-9- (3-methylbenzyl) -9H-purine (designated as Compound 2) was obtained by column chromatography purification in 72% yield. The nuclear magnetic hydrogen spectrum, carbon spectrum and high resolution mass spectrum data of compound 2 are as follows: ¹ H NMR(500MHz，CDCl ₃ )δ8.45(s，1H)，7.22–7.04(m，4H)，5.19(s，2H)，4.22(s，3H)，4.15(s，3H)，2.30(s，3H). ¹³ C NMR(126MHz，CDCl ₃ )δ158.32，156.73，152.15，150.32，138.49，135.66，128.76，128.63，128.30，124.73，117.71，57.52，53.95，44.85，21.36.HR-MS(ESI)calcd for C ₁₄ H ₁₇ N ₄ O ₂ ，[M+H] ⁺ :285.1352, found:285.1351. the structure of compound 2 is shown below:

example 3

The specific preparation steps of compound 3 are as follows:

a10 ml tube was sealed with a dry magnet and 9-benzyl-6-methoxy-9H-purine (0.1 mmol,0.0241 g), isopropanol (1 mmol,0.0601 g) and Acr was added ⁺ –Mes ClO ₄ ^- (3 mol%,0.0012 g), TFA (0.5 mmol,0.0570 g), and 2mL dichloroethane solvent. The reaction tube was placed in a 20W LED (450 nm to 465 nm) under air conditions and irradiated at room temperature for 18 hours. The reaction was followed by TLC, after the termination of the reaction, the solvent was concentrated in vacuo and the target product 9-benzyl-6-methoxy-8-isopropoxy-9H-purine (designated as Compound 3) was purified by column chromatography in 63% yield. The nuclear magnetic hydrogen spectrum, carbon spectrum and high resolution mass spectrum data of compound 3 are as follows: ¹ H NMR(400MHz，CDCl ₃ )δ8.43(s，1H)，7.37–7.22(m，5H)，5.47(p，J＝6.2Hz，1H)，5.21(s，2H)，4.14(s，3H)，1.41(d，J＝6.2Hz，6H). ¹³ C NMR(101MHz，CDCl ₃ )δ158.12，155.71，151.89，149.96，135.95，128.65，127.99，127.95，117.91，74.68，53.93，44.85，22.00.HR-MS(ESI)calcd for C ₁₆ H ₁₉ N ₄ O ₂ ，[M+H] ⁺ :299.1508, found:299.1508. the structure of compound 3 is shown below:

example 4

The specific preparation steps of compound 4 are as follows:

a10 ml tube was sealed with a dry magnet added thereto, 9-benzyl-6-methoxy-9H-purine (0.1 mmol,0.0241 g), n-dodecanol (2 mmol,0.3720 g) and Acr were added ⁺ –Mes ClO ₄ ^- (4 mol%,0.0016 g), TFA (0.2 mmol,0.0228 g), and 2mL MeCN solvent. The reaction tube was placed in a 20W LED (450 nm to 465 nm) under air conditions and irradiated at room temperature for 24 hours. The reaction was followed by TLC, after the termination of the reaction, the solvent was concentrated in vacuo and the target product 9-benzyl-8- (dodecyloxy) -6-methoxy-9H-purine (designated as Compound 4) was purified by column chromatography in 61% yield. The nuclear magnetic hydrogen spectrum, carbon spectrum, and high resolution mass spectrum data of compound 4 are as follows: ¹ H NMR(400MHz，CDCl ₃ )δ8.41(s，1H)，7.39–7.06(m，5H)，5.19(s，2H)，4.55(t，J＝6.6Hz，2H)，4.12(s，3H)，1.82–1.74(m，2H)，1.36-1.22(m，18H)，0.86(t，J＝6.7Hz，3H). ¹³ C NMR(101MHz，CDCl ₃ )δ158.19，156.23，151.97，150.16，150.06，135.84，128.67，128.64，127.91，117.77，70.86，70.81，70.75，53.95，53.78，44.90，31.88，29.60，29.52，29.32，29.15，28.75，25.66，22.65，14.12，14.03.HR-MS(ESI)calcd for C ₂₅ H ₃₇ N ₄ O ₂ ，[M+H] ⁺ :425.2917, found:425.2919. the structure of compound 4 is shown below:

example 5

The specific preparation steps of compound 5 are as follows:

a10 mL tube was capped with dry magneton and 9-benzyl-6-methoxy-9H-purine (0.1 mmol,0.0241 g), ethylene glycol (0.2 mmol,0.0124 g), TPT (5 mol%,0.0019 g), TFA (0.2 mmol,0.0228 g), and 2mL MeCN solvent were added. The reaction tube was placed in a 20W LED (450 nm to 465 nm) under air conditions and irradiated at room temperature for 24 hours. The reaction is followed by TLC, after the reaction is terminated, the solvent is concentrated in vacuo, and the target product 2- ((9-benzyl-6-methoxy-9H-purine) is obtained by column chromatography purification-8-yl) oxy) ethanol (designated compound 5) in a yield of 51%. The nuclear magnetic hydrogen spectrum, carbon spectrum and high resolution mass spectrum data of compound 5 are as follows: ¹ H NMR(400MHz，CDCl ₃ )δ8.47(s，1H)，7.36–7.23(m，5H)，5.26(s，2H)，4.73–4.65(m，2H)，4.15(s，3H)，3.98–3.92(m，2H). ¹³ C NMR(101MHz，CDCl ₃ )δ158.40，156.21，152.01，150.52，135.69，128.85，128.18，127.81，117.39，72.58，61.41，54.03，45.07.HR-MS(ESI)calcd for C ₁₅ H ₁₇ N ₄ O ₃ ，[M+H] ⁺ :301.1301, found:301.1305. the structure of compound 5 is shown below:

example 6

The specific preparation steps of compound 6 are as follows:

a10 ml tube was sealed with a dry magnet and 9-benzyl-6-methoxy-9H-purine (0.1 mmol,0.0241 g), cyclohexanol (1 mmol,0.0100 g) and Acr were added ⁺ –Mes ClO ₄ ^- (3 mol%,0.0012 g), acetic acid (0.2 mmol,0.0120 g), and 2mL MeCN solvent. The reaction tube was placed in a 20W LED (450 nm to 465 nm) under air conditions and irradiated at room temperature for 18 hours. The reaction was followed by TLC, after the termination of the reaction, the solvent was concentrated in vacuo and the target product 9-benzyl-8- (cyclohexyloxy) -6-methoxy-9H-purine (designated as Compound 6) was purified by column chromatography in 75% yield. The nuclear magnetic hydrogen spectrum, carbon spectrum, and high resolution mass spectrum data of compound 7 are as follows: ¹ H NMR(400MHz，CDCl ₃ )δ8.42(s，1H)，7.38–7.21(m，5H)，5.26(tt，J＝8.1，3.8Hz，1H)，5.21(s，2H)，4.14(s，3H)，2.00(dd，J＝11.8，5.8Hz，2H)，1.75–1.24(m，8H). ¹³ C NMR(101MHz，CDCl ₃ )δ158.05，155.71，151.93，149.92，135.98，128.64，128.00，127.94，117.89，78.87，53.91，44.90，31.45，25.27，23.26.HR-MS(ESI)calcd for C ₁₉ H ₂₃ N ₄ O ₂ ，[M+H] ⁺ 339.1821, found:339.1822. The structure of Compound 6 is as followsThe following is shown:

example 7

The specific preparation steps of compound 7 are as follows:

a10 ml tube was sealed with a dry magnet added thereto, 9-benzyl-6-methoxy-9H-purine (0.1 mmol,0.0240 g), ethylene glycol monomethyl ether (1 mmol,0.0760 g) and Acr were added ⁺ –Mes ClO ₄ ^- (3 mol%,0.0012 g), TFA (0.2 mmol,0.0228 g), TBHP (0.2 mmol,0.0180 g) and 2mL dichloromethane solvent. The reaction tube was placed in a 5W LED (450 nm to 465 nm) under air conditions and irradiated at room temperature for 24 hours. The reaction was followed by TLC, after the termination of the reaction, the solvent was concentrated in vacuo and the target product 9-benzyl-6-methoxy-8- (2-methoxyethoxy) -9H-purine (designated as compound 7) was purified by column chromatography in 72% yield. The nuclear magnetic hydrogen spectrum, carbon spectrum, and high resolution mass spectrum data of compound 7 are as follows: ¹ H NMR(400MHz，CDCl ₃ )δ8.44(s，1H)，7.48–7.18(m，5H)，5.24(s，2H)，4.84–4.61(m，2H)，4.13(s，3H)，3.83–3.70(m，2H)，3.38(s，3H). ¹³ C NMR(101MHz，CDCl ₃ )δ158.31，155.96，152.00，150.28，135.77，128.68，128.08，128.00，117.68，70.32，69.59，58.93，53.97，45.01.HR-MS(ESI)calcd for C ₁₆ H ₁₉ N ₄ O ₃ ，[M+H] ⁺ 315.1457, found 315.1460. The structure of compound 7 is shown below:

example 8

The specific preparation steps of compound 8 are as follows:

a10 ml tube was sealed with a dry magnet added thereto, ethyl 2- (6-methoxy-9H-purin-9-yl) acetate (0.1 mmol,0.0236 g), methanol (4 mmol,0.1280 g) and Acr were added ⁺ –Mes ClO ₄ ^- (3 mol%,0.0012 g), pivalic acid (0.2)mmol,0.0210 g), and 2mL MeCN solvent. The reaction tube was placed in a 20W LED (450 nm to 465 nm) under air conditions and irradiated at room temperature for 18 hours. The reaction was followed by TLC, after the termination of the reaction, the solvent was concentrated in vacuo and the target product, ethyl 2- (6, 8-dimethoxy-9H-purin-9-yl) acetate (designated compound 8), was purified by column chromatography in 73% yield. The nuclear magnetic hydrogen spectrum, carbon spectrum and high resolution mass spectrum data of compound 8 are as follows: ¹ H NMR(500MHz，CDCl ₃ )δ8.40(s，1H)，4.80(s，2H)，4.28–4.19(m，5H)，4.16(s，3H)，1.28(t，J＝7.1Hz，3H). ¹³ C NMR(126MHz，CDCl ₃ )δ166.86，158.36，156.44，151.99，150.31，117.83，77.35，77.30，77.10，76.84，62.03，57.60，53.99，42.08，14.03.HR-MS(ESI)calcd for C ₁₁ H ₁₅ N ₄ O ₄ ，[M+H] ⁺ 267.1093, found:267.1093. The structure of compound 8 is shown below:

example 9

The specific preparation steps of compound 9 are as follows:

a10 ml tube was sealed with a dry magnet added thereto, 9-ethyl-6-methoxy-9H-purine (0.1 mmol,0.0178 g), methanol (1 mmol,0.0320 g) and Acr were added ⁺ –Mes ClO ₄ ^- (5 mol%,0.0020 g), TFA (0.2 mmol,0.0228 g), 2mL tetrahydrofuran solvent. The reaction tube was placed in a 20W LED (450 nm-465 nm) under oxygen for 18h of irradiation reaction at room temperature. The reaction was followed by TLC, after the completion of the reaction, the solvent was concentrated in vacuo and the target product 9-ethyl-6, 8-dimethoxy-9H-purine (designated as Compound 9) was obtained by column chromatography purification in 70% yield. The nuclear magnetic hydrogen spectrum, carbon spectrum, and high resolution mass spectrum data of compound 9 are as follows: ¹ H NMR(400MHz，CDCl ₃ )δ8.39(s，1H)，4.21(s，3H)，4.13(s，3H)，4.09(q，J＝7.2Hz，2H)，1.38(t，J＝7.2Hz，3H). ¹³ C NMR(101MHz，CDCl ₃ )δ158.22，156.68，151.90，150.01，117.73，57.34，53.88，36.58，14.40.HR-MS(ESI)calcd forC ₉ H ₁₃ N ₄ O ₂ ，[M+H] ⁺ 209.1039, found:209.1039. The structure of compound 9 is shown below:

/>

the 8-alkoxypurine derivatives prepared in examples 1-9 have important medicinal values and can be applied to the preparation of antitumor drugs, antiviral drugs or antibacterial drugs.

The foregoing examples are illustrative of the present invention and are not intended to be limiting, but rather, the invention is intended to be limited to the specific embodiments shown, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principles of the invention are intended to be equivalent substitutes and modifications within the scope of the invention.

Claims (1)

1. A process for the preparation of an 8-alkoxypurine derivative, characterized in that: the method comprises the following steps:

mixing 8H-purine derivatives with alcohol, a photocatalyst, an oxidant, carboxylic acid or derivatives thereof, and reacting under the illumination condition to obtain the 8-alkoxypurine derivatives;

the structure of the 8H-purine derivative is shown as a formula (II);

in the formula (II), R ⁴ Selected from substituted or unsubstituted alkoxy groups; r is R ⁵ Selected from substituted or unsubstituted alkyl, alkoxycarbonylalkyl;

the alcohol is at least one selected from methanol, ethanol, isopropanol, butanol, n-dodecanol, cyclohexanol, ethylene glycol and ethylene glycol monomethyl ether;

the molar ratio of the 8H-purine derivative to the alcohol is 1: (2-50);

the molar ratio of the 8H-purine derivative to the photocatalyst, the oxidant, the carboxylic acid or the derivative thereof is 1: (0.02-0.06): (1-3):

(1-6)；

the photocatalyst is at least one selected from 10-methyl-9-mesityl acridine perchlorate and 2,4, 6-triphenylpyrylium tetrafluoroborate;

the wavelength of the illumination light is 450nm-480nm;

the carboxylic acid or the derivative thereof is at least one selected from trifluoroacetic acid, acetic acid, propionic acid, butyric acid, levulinic acid and pivalic acid;

the oxidant is at least one selected from air, oxygen, di-tert-butyl peroxide and tert-butyl hydroperoxide;

the solvent for the reaction is at least one selected from nitrile solvents and halogenated hydrocarbon solvents;

the temperature of the reaction is 15-40 ℃;

the reaction time is 8-36 h.

Images