Phenazine statin compound as well as preparation method and application thereof

Abstract

The invention relates to the technical field of medicines, relates to a phenazine statin compound as well as a preparation method and application thereof, and in particular relates to a phenazine statin compound as well as a preparation method and application thereof. The invention provides a phenazine statin compound as shown in a general formula I, II or III or pharmaceutically acceptable salt thereof, and R1, R2, R3 and R4 are described in the claims and the specification. The compound provided by the invention has obvious anti-tumor or antibacterial activity. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and relates to phenazinastatin compounds, their preparation methods and applications, and specifically relates to phenazinastatin compounds, their preparation methods and applications in the preparation of antibacterial and anti-tumor drugs. Background Art

[0002] Phenazinastatin compounds are mainly derived from the strain Cystobasidium laryngis of the genus Cystobasidium, which is mainly distributed in sedimentary rocks more than 4 kilometers deep in the Indian Ocean, and it is difficult to collect.

[0003] At present, the content of phenazinastatin compounds in nature is low (the content of some compounds in the fermentation broth is less than 30 micrograms per liter), the number of currently discovered phenazinastatin compounds is small, and there is no reported artificial total synthesis preparation method for them. There is no general method to synthesize compounds with various different substitution conditions. Moreover, there is no relevant report on the application of derivatives of such structures in the preparation of antibacterial and anti-tumor drugs. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to overcome the defects of the prior art and provide a series of new phenazinastatin compounds, and the phenazinastatin compounds have obvious antibacterial and anti-tumor activities.

[0005] The present invention is achieved as follows:

[0006] The present invention provides phenazinastatin compounds represented by general formula I, II or III or pharmaceutically acceptable salts thereof:

[0007]

[0008] Wherein,

[0009] R 1 is H, OH, C1-C6 alkyl, C1-C6 alkoxy, COOR 5 , halogen;

[0010] R 2 is H, TBS, C2-C6 alkenyl;

[0011] R 3 is H, C1-C6 alkyl, C1-C6 alkoxy, halogen;

[0012] R 4 is H, OH, C1-C6 alkyl, C1-C6 alkoxy, COOR 5 , halogen;

[0013] R 5is H, C1-C6 alkyl, C2-C6 alkenyl, unsubstituted or halogen-substituted phenyl,

[0014] The present invention preferably relates to phenazinastatin compounds represented by general formula I, II or III or pharmaceutically acceptable salts thereof:

[0015] wherein,

[0016] R 1 is H, OH, C1-C4 alkyl, C1-C4 alkoxy, COOR 5 、halogen;

[0017] R 2 is H, TBS, C2-C4 alkenyl;

[0018] R 3 is H, C1-C4 alkyl, C1-C4 alkoxy, halogen;

[0019] R 4 is H, OH, C1-C4 alkyl, C1-C4 alkoxy, COOR 5 、halogen;

[0020] R 5 is H, C1-C4 alkyl, C2-C4 alkenyl, unsubstituted or halogen-substituted phenyl,

[0021] The present invention preferably relates to the following phenazinastatin compounds or pharmaceutically acceptable salts thereof:

[0022] wherein,

[0023] In formula I,

[0024] R 1 is H, OH, C1-C4 alkyl, C1-C4 alkoxy, COOR 5 、bromine;

[0025] R 2 is H, TBS, C2-C4 alkenyl;

[0026] R 5 is H, C1-C4 alkyl, C2-C4 alkenyl, chlorine-substituted phenyl,

[0027] In formula II,

[0028] R 3 is H, C1-C4 alkoxy, bromine;

[0029] In formula III,

[0030] R 4is H, OH, C1-C4 alkoxy, COOR 5 , bromine;

[0031] R 5 is H or

[0032] The present invention preferably provides the following phenazinastatin compounds or their pharmaceutically acceptable salts:

[0033]

[0034] Furthermore, the present invention provides a preparation method of the phenazinastatin compounds shown by general formula I, II or III. General formula II can be prepared by the nucleophilic addition reaction and the reduction dehydration reaction of aniline and the corresponding nitrobenzene. General formula I can be prepared on the basis of general formula III through the keto group asymmetric reduction reaction and the protecting group reaction on the hydroxyl group. General formula III can be obtained by oxidation on the basis of general formula I or general formula II; for details, see the examples.

[0035] The present invention provides a pharmaceutical composition comprising the phenazinastatin compounds shown by general formula I, II or III or their pharmaceutically acceptable salts and a pharmaceutically acceptable carrier or excipient.

[0036] The present invention further provides the use of the phenazinastatin compounds shown by general formula I, II or III or their pharmaceutically acceptable salts and their pharmaceutical compositions in the preparation of antibacterial and anti-tumor drugs.

[0037] The antibacterial drug described above is an antibacterial or antifungal drug.

[0038] The bacteria described above are methicillin-resistant Staphylococcus aureus, and the fungi are Trichophyton rubrum, Trichophyton mentagrophytes, Candida albicans, Cryptococcus neoformans, etc.

[0039] The tumors described above are colon cancer, pancreatic cancer, prostate cancer, breast cancer or liver cancer. Detailed implementation manners

[0040] The following further illustrates the present invention with specific examples, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the technical field.

[0041] Among them, the information of the reagents and instruments used in this example is as follows:

[0042] Reagents: 2-ethylamine, 2-methoxy-nitrobenzene, 2-bromo-nitrobenzene, tert-butyl hydroperoxide, ferrous chloride, acetonitrile, N,N-dimethylformamide, Dess-Martine salt, N,O-bis(trimethylsilyl)acetamide, palladium acetate, formic acid, tetrabutylammonium fluoride, potassium tert-butoxide, methyl iodide, TBSCl, THF, silica gel, potassium carbonate, methanol, petroleum ether, ethyl acetate, dichloromethane, etc.

[0043] Instruments: ABI Maldi-TOF and Qstar Elite high-resolution mass spectrometry systems; Bruker Avance 600MHz nuclear magnetic resonance spectrometer (Bruker Corporation, Switzerland); Agilent GC-MS; EYLA (SB-1200) rotary evaporator (Shanghai Ailan Instruments Co., Ltd.); -MAG HS 7 magnetic stirrer (Shanghai Ailan Instruments Co., Ltd.); YUHUA (ZF-20D AN) dark box type ultraviolet analyzer (Shanghai Guanghao Analytical Instruments Co., Ltd.); KQ5200E ultrasonic cleaner (Kunshan Ultrasonic Instruments Co., Ltd.), SB-1200 water bath (Shanghai Ailan Instruments Co., Ltd.), A-1000S water aspirator (Shanghai Ailan Instruments Co., Ltd.).

[0044] Preparation of Compounds 1-19 in Example 1

[0045] 1. Synthesis of Target Compounds 1 and 2 (Taking 1 as an Example)

[0046]

[0047] Place a 100 mL single-necked flask, add a magnetic stir bar, evacuate, and introduce argon. Inject 60 mL of potassium tert-butoxide (1 mol / L) into it. Place it in a low-temperature reactor at -35 °C. Dropwise add 2.44 g (20.0 mmol) of 2-ethylaniline, stir for 10 minutes, then cool to -60 °C, and then dropwise add 3.1 g (20.0 mmol) of 2-methoxy-nitrobenzene. Stir at this temperature for 2 hours, then add 100 mL of saturated ammonium chloride solution to quench the reaction. Then add 100.0 mL of ethyl acetate for extraction, concentrate the organic layer, and separate and purify it by silica gel column chromatography to obtain the target compound 1a (2.7 g, 52% yield). The eluent is (petroleum ether / ethyl acetate = 9:1). The physicochemical data of the compound are as follows:

[0048] N-(2-Ethylphenyl)-3-methoxy-2-nitrosoaniline (1a): Red solid, mp 148 - 150 °C. 1 H-NMR (600MHz, CDCl 3)δ13.26(s,1H),7.33(d,J=7.3Hz,1H),7.26 - 7.29(m,2H),7.24(d,J=3.8Hz,2H),6.35(d,J=8.9Hz,1H),6.30(d,J=7.9Hz,1H),4.14(s,3H),2.58(q,J=7.6Hz,2H),1.19(t,J=7.6Hz,3H). 13 C - NMR(150MHz,CDCl 3 )δ163.2,150.1,140.8,139.7,135.3,134.5,129.5,127.4,126.9,126.6,106.7,97.5,56.4,24.5,14.5.HRMS(ESI)calcd.for[C 15 H 16 N 2 O 2 +Na] + 279.1109,found 279.1108.

[0049] 1a (1.65 g, 6.4 mmol) was placed in a 100 - mL single - necked flask, a magnetic stir bar was added, the flask was evacuated and then filled with argon. 20 mL of DMF was injected into it and stirred. 2.44 g (BSA, 7.5 mL) of N,O - bis(trimethylsilyl)acetamide was added dropwise, the temperature was raised to 60 °C, and then stirred overnight. Finally, 200 mL of ice - water was added to quench the reaction. The yellow solid was filtered by suction, and the yellow solid was recrystallized from ethyl acetate to obtain the target compound 1 (1.0 g, 70.0%). Compound 2 can be prepared by the same method. The physicochemical data of the compounds are as follows:

[0050]

[0051] 1 - Ethyl - 6 - methoxyphenazine(1): Yellow solid, mp 164 - 166 °C. 1 H - NMR(600MHz,CDCl 3 )δ8.25(d,J=8.7Hz,1H),7.89(d,J=8.8Hz,1H),7.76(dt,J=13.3,7.6Hz,2H),7.68(d,J=6.8Hz,1H),7.09(d,J=7.5Hz,1H),4.20(s,3H),3.46(q,J=7.5Hz,2H),1.48(t,J=7.5Hz,3H). 13 C - NMR(150MHz,CDCl 3)δ155.0,143.5,143.4,142.6,142.4,136.4,130.2,129.8,128.1,128.0,122.0,106.3,56.5,24.1,14.7.HRMS(ESI)calcd.for[C 15 H 14 N 2 O+Na] + 261.1004,found 261.1007.1-Bromo-6-ethylphenazine(2):Yellow solid,mp 160 - 162℃. 1 H NMR(600MHz,CDCl 3 )δ8.29(d,J=8.7Hz,1H),8.25(d,J=8.7Hz,1H),8.21 - 8.19(m,1H),7.84(dd,J=8.6,6.9Hz,1H),7.72(d,J=6.7Hz,1H),7.69(dd,J=8.5,7.4Hz,1H),3.46(q,J=7.5Hz,2H),1.48(t,J=7.5Hz,3H). 13 C NMR(150MHz,CDCl 3 )δ143.9,143.5,143.1,142.9,140.4,133.4,131.2,130.2,129.7,128.6,127.8,124.1,24.2,14.7.HRMS(ESI)calcd.for[C 14 H 11 BrN 2 +Na] + 309.0003,found 309.0005.

[0052] 2. Synthesis of target compounds 3 and 4 (taking 3 as an example)

[0053]

[0054] Take a 100 mL single-necked flask and place in it Compound 1 (2.7 g, 11.0 mmol), ferrous chloride (0.15 g, 1.2 mmol), a magnetic stir bar, 20.0 mL of acetonitrile, 20.0 mL of water, and 30.0 mL of tert-butyl hydroperoxide (TBHP, 70% aqueous solution). Stir at 80 °C for 12 hours, then add an additional 5 mL of tert-butyl hydroperoxide and continue stirring at 80 °C for 12 hours. Remove the organic solvent by rotary evaporation, then add 50 mL of water and extract with 100.0 mL of EtOAc. Concentrate the organic solvent layer, pass through a silica gel column, and separate and purify to obtain Compound 3 (0.8 g, 30.0%). Compound 4 can be prepared in the same manner. The physicochemical data of the compounds are as follows: 1-(6-methoxyphenazin-1-yl)ethan-1-one (3): Yellow solid, mp 175 - 177 °C. 1 H-NMR(600MHz,CDCl 3 )δ8.57(d,J=8.7Hz,1H),8.22(d,J=6.9Hz,1H),7.89(t,J=8.7Hz,2H),7.83(t,J=8.1Hz,1H),7.15(d,J=7.4Hz,1H),4.23(s,3H),3.12(s,3H). 13 C-NMR(150MHz,CDCl 3 )δ201.8,155.1,143.8,141.6,141.2,139.0,136.6,134.0,131.7,131.2,129.4,121.8,107.0,56.6,33.0.HRMS(ESI)calcd.for[C 15 H 12 N 2 O 2 +Na] + 275.0796,found275.0799.

[0055] 1-(6-Bromophenazin-1-yl)ethan-1-one (4): Yellow solid, mp 170 - 172 °C. 1 HNMR(600MHz,CDCl 3 )δ8.50(d,J=8.7Hz,1H),8.21(dd,J=10.6,6.6Hz,3H),7.92(dd,J=8.4,7.2Hz,1H),7.73-7.70(m,1H),3.09(s,3H). 13 C NMR(150MHz,CDCl 3)δ201.3,143.3,143.0,141.3,140.5,138.9,134.2,133.9,132.2,130.9,130.2,129.9,124.3,33.0.HRMS(ESI)calcd.for[C 14 H 9 BrN 2 O+Na] + 322.9796,found 322.9798.

[0056] In addition, Compounds 3 and 4 can also be prepared by alternative methods (taking Compound 4 as an example):

[0057]

[0058] Take a 100 mL single-necked flask and place Compound 2 (110.0 mg, 0.4 mmol), potassium carbonate (40.0 mg, 0.28 mmol), rhodium caprolactamate ((Rh 2 (cap) 4 , 1.5 mg, 0.002 mmol), a magnetic stir bar, 10.0 mL of dichloromethane, and 0.3 mL of tert-butyl hydroperoxide (TBHP, 70% aqueous solution). Heat under reflux and, every 6 hours, add the same amount of rhodium caprolactamate and tert-butyl hydroperoxide as before. Operate continuously for 5 times. Cool, then add 50 mL of water, extract with 50.0 mL of dichloromethane, concentrate the organic solvent layer, and purify by silica gel column chromatography to obtain Compound 4 (57 mg, 50.0%). Compound 3 can be prepared in the same manner.

[0059] 3. Synthesis of the target compound 5

[0060]

[0061] Place the S-Corey-Bakshi-Shibata (S-CBS) reagent (36 mg, 0.13 mmol) in a 25 mL dry single-necked flask, add a stir bar, and evacuate. Inject 2.5 mL of dry tetrahydrofuran and add argon. Dropwise add a solution of borane in tetrahydrofuran (1 mol / L, 0.8 mL) and stir for 10 minutes. Then, at 0 °C, dropwise add a solution of Compound 4 in tetrahydrofuran (0.27 g, 0.9 mmol, dissolved in 13.0 mL of THF). Stir at 25 °C for 2 hours, and then monitor the reaction by TLC until it is complete. Distill off the THF, add 50.0 mL of H 2 O, extract with 50 mL of ethyl acetate, separate the organic solvent layer, concentrate, and purify the extract by silica gel column chromatography to obtain 5 (0.25 g, 90.0%). The eluent is petroleum ether / ethyl acetate (v / v = 9:1). The physicochemical data of the compound are as follows:

[0062] (R)-1-(6-Bromophenazin-1-yl)ethan-1-ol(5): Yellow solid, mp: 190 - 192 °C. 1 H NMR(600MHz, CDCl 3 ) δ8.23(dd, J=8.4, 1.0Hz, 1H), 8.15(d, J=7.2Hz, 1H), 8.12(d, J=8.6Hz, 1H), 7.80(dd, J=8.4, 8.6Hz, 1H), 7.77(d, J=7.6Hz, 1H), 7.64(dd, J=8.3, 7.5Hz, 1H), 5.69(q, J=6.6Hz, 1H), 1.77(d, J=6.6Hz, 3H). 13 C NMR(150MHz, CDCl 3 ) δ143.9, 142.6, 141.8, 141.8, 140.4, 133.7, 130.9, 130.5, 129.4, 129.1, 127.4, 124.3, 68.4, 23.6. HRMS(ESI) calcd. for [C 14 H 11 BrN 2 O+Na] + 324.9952, found 324.9954.

[0063] 4. Synthesis of the target compound 6

[0064]

[0065] Compound 5 (320 mg, 1.06 mmol), imidazole (0.98 g, 14.0 mmol), and DMAP (39 mg, 0.32 mmol) were placed in a 100 mL single-neck flask, a magnetic stir bar was added, and the flask was evacuated. Then dichloromethane (18.0 mL) was injected, and argon was added. TBSCl (0.65 g, 4.3 mmol, dissolved in 7 mL of DCM) was added dropwise at room temperature, and the mixture was stirred overnight. The reaction was quenched by adding 50.0 mL of water, and then extracted with dichloromethane (30 mL). The organic layer was separated, concentrated, and the residue was purified by silica gel column chromatography to obtain 6 (0.38 g, 85.0%), and the eluent was petroleum ether / ethyl acetate (v / v = 10:1). The physicochemical data of the compound are as follows:

[0066] (R)-1-Bromo-6-(1-((tert-butyldimethylsilyl)oxy)ethyl)phenazine(6): Yellow solid, mp: 164 - 166 °C.1 H NMR (600 MHz, CDCl 3 ) δ 8.29 (d, J = 3.2 Hz, 1H), 8.27 (d, J = 3.2 Hz, 1H), 8.20 (d, J = 7.2 Hz, 1H), 8.11 (d, J = 6.8 Hz, 1H), 7.92 (dd, J = 8.5, 7.1 Hz, 1H), 7.71 - 7.68 (m, 1H), 6.20 (q, J = 6.3 Hz, 1H), 1.64 (d, J = 6.3 Hz, 3H), 0.98 (s, 9H), 0.16 (s, 3H), 0.05 (s, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 145.7, 143.5, 142.9, 141.1, 140.4, 133.4, 131.3, 130.1, 129.8, 128.3, 126.9, 124.2, 66.2, 26.6, 26.0, 18.3, -4.6, -4.7. HRMS (ESI) calcd. for [C 20 H 25 BrN 2 OSi + Na] + 439.0817, found 439.0812.

[0067] 5. Synthesis of target compounds 7 and 8

[0068]

[0069] Compound 6 (78.0 mg, 0.18 mmol), palladium acetate (2.0 mg, 0.009 mmol), 4,5 - bis(diphenylphosphino)-9,9 - dimethyloxanthrene (Xantphos, 5.0 mg, 0.009 mmol) were placed in a 25 - mL single - necked flask, a magnetic stir bar was added, and the flask was evacuated. Then toluene (4.0 mL), formic acid (50.0 mg, 1.0 mmol), and triethylamine (0.05 mL) were injected respectively, and the reaction was protected with argon. The mixture was stirred at 80 °C overnight. The reaction was quenched by adding 50.0 mL of water, and then extracted with ethyl acetate (50.0 mL). The organic layer was separated, concentrated, and the residue was purified by silica gel column chromatography to obtain 7 (32.0 mg, 45.0%) and 8 (9.0 mg, 15.0%). The eluent was petroleum ether / ethyl acetate (v / v = 10:1 - 5:1). The physicochemical data of the compounds are as follows:

[0070] (R)-6-(1-((Tert-butyldimethylsilyl)oxy)ethyl)phenazine-1-carboxylic acid(7): Yellow solid, mp: 170 - 172 °C. 1 H NMR(600MHz, CDCl 3 ) δ 15.72(s, 1H), 8.99(dd, J=7.0, 1.2Hz, 1H), 8.59(dd, J=8.7, 1.2Hz, 1H), 8.20(d, J=6.9Hz, 1H), 8.17(d, J=8.7Hz, 1H), 8.02 - 8.06(m, 2H), 6.21(q, J=6.3Hz, 1H), 1.66(d, J=6.3Hz, 3H), 0.99(s, 9H), 0.18(s, 3H), 0.07(s, 3H). 13 C NMR(150MHz, CDCl 3 ) δ 166.2, 146.6, 142.3, 141.4, 139.8, 139.7, 137.1, 135.4, 133.5, 129.9, 127.4, 126.2, 124.8, 66.0, 26.7, 25.9, 18.3, -4.7, -4.8. HRMS(ESI) calcd. for [C 21 H 26 N 2 O 3 Si + Na] + 405.1610, found 405.1611.

[0071] (R)-1-(1-((Tert-butyldimethylsilyl)oxy)ethyl)phenazine(8): Yellow solid, mp: 264 - 266 °C. 1 H NMR(600MHz, CDCl 3 ) δ 8.32 - 8.28(m, 1H), 8.26(dd, J=6.3, 3.7Hz, 1H), 8.14(d, J=8.7Hz, 1H), 8.07(d, J=6.9Hz, 1H), 7.89 - 7.87(m, 1H), 7.87 - 7.83(m, 2H), 6.24(q, J=6.3Hz, 1H), 1.66(d, J=6.3Hz, 3H), 0.99(s, 9H), 0.16(s, 3H), 0.06(s, 3H). 13 C NMR(150MHz, CDCl 3)δ146.0,143.2,142.9,142.5,140.9,130.7,130.3,130.2,129.9,129.4,127.8,126.0,66.2,26.7,26.0,18.3,-4.7,-4.8.HRMS(ESI)calcd.for[C 20 H 26 N 2 OSi+Na] + 361.1712,found 361.1710.

[0072] 6. Synthesis of target compound 9

[0073]

[0074] Compound 6 (78.0 mg, 0.18 mmol), palladium acetate (2.0 mg, 0.009 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 5.0 mg, 0.009 mmol) were placed in a 25 mL single-necked flask, a magnetic stir bar was added, and the flask was evacuated. Then toluene (2.0 mL) and triethylamine (0.05 mL) were injected respectively, and the reaction was protected with argon. Then 2,4,6-trichlorophenyl formate (122.0 mg, 0.54 mmol, dissolved in 3.0 mL toluene) was added, and the mixture was stirred at 100 °C overnight. The reaction was quenched by adding 50.0 mL of water, and then extracted with ethyl acetate (50.0 mL). The organic solvent layer was separated, concentrated, and the residue was purified by silica gel column chromatography to obtain 9 (55.0 mg, 55.0%), and the eluent was petroleum ether / ethyl acetate (v / v = 10:1). Compound 9 can also be synthesized from compound 6 catalyzed by tris(dibenzylideneacetone)dipalladium(0) (Pd 2 (dba) 3 ) (under the same other conditions), and the yield of this step (65.0%) is better than that of palladium acetate. The physicochemical data of compound 9 are as follows:

[0075] 2,4,6-Trichlorophenyl (R)-6-(1-((tert-butyldimethylsilyl)oxy)ethyl)phenazine-1-carboxylate (9): Yellow solid, mp: 170 - 172 °C. 1 H NMR (600 MHz, CDCl 3)δ8.65(dd,J=6.9,1.3Hz,1H),8.55(dd,J=8.7,1.3Hz,1H),8.23(d,J=8.7Hz,1H),8.11(d,J=6.9Hz,1H),7.95(dd,J=8.7,7.0Hz,1H),7.91(dd,J=8.6,7.0Hz,1H),7.51(s,2H),6.23(q,J=6.3Hz,1H),1.65(d,J=6.3Hz,3H),0.98(s,9H),0.16(s,3H),0.06(s,3H). 13 C NMR(150MHz,CDCl 3 )δ162.1,145.9,143.9,143.3,141.7,140.8,135.5,133.7,132.2,131.5,130.0,128.9(2C),128.8(2C),128.5,128.4,128.1,127.0,66.1,26.7,26.0,18.3,-4.7,-4.8.HRMS(ESI)calcd.for[C 27 H 27 Cl 3 N 2 O 3 Si+Na] + 583.0754,found583.0757.

[0076] 7. Synthesis of Target Compound 10

[0077]

[0078] Place compound 9 (28.0 mg, 0.05 mmol) in a 25 mL single-necked flask, add a magnetic stir bar, and then add tetrahydrofuran (6.0 mL). At 0 °C, add tetrabutylammonium fluoride solution (TBAF, 1 mol / L, 0.5 mL). Remove the ice bath after 20 minutes and stir at room temperature overnight. Remove THF using a rotary evaporator at room temperature, add 30.0 mL of water and 30.0 mL of ethyl acetate for extraction. Separate the organic solvent layer, concentrate it, and purify the residue by silica gel column chromatography to obtain 10 (12.0 mg, 90.0%), with the eluent being petroleum ether / ethyl acetate (v / v = 10:1 - 5:1). Compound 10 can also be prepared from compound 7 under the same conditions, and the yield of this step is similar. The physical and chemical data of compound 10 are as follows:

[0079] (R)-6-(1-Hydroxyethyl)phenazine-1-carboxylic acid (10): Yellow solid, mp: 170 - 172 °C.1 H NMR (600 MHz, CDCl 3 ) δ 15.48 (s, 1H), 9.02 (dd, J = 7.0, 1.2 Hz, 1H), 8.55 (dd, J = 8.7, 1.1 Hz, 1H), 8.22 (dd, J = 8.6, 0.9 Hz, 1H), 8.09 (dd, J = 8.4, 7.3 Hz, 1H), 8.02 (dd, J = 8.4, 7.1 Hz, 1H), 7.98 (d, J = 6.8 Hz, 1H), 5.87 (q, J = 6.6 Hz, 1H), 1.84 (d, J = 6.6 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 165.8, 143.8, 142.3, 141.6, 140.4, 139.8, 137.5, 134.9, 133.3, 130.5, 127.8, 127.1, 124.9, 68.0, 23.9. HRMS (ESI) calcd. for [C 15 H 12 N 2 O 3 +Na] + 291.0746, found 291.0745.

[0080] 8. Synthesis Scheme of Target Compounds 11 and 12 (Taking Compound 11 as an Example)

[0081]

[0082] Place compound 7 (50.0 mg, 0.13 mmol) in a 25 mL single-necked flask, weigh potassium carbonate (54.0 mg, 0.4 mmol), add a magnetic stir bar, then add DMF (5.0 mL). At 0 °C, add methyl iodide (28.0 mg, 0.2 mmol) dropwise. After 20 minutes, remove the ice bath and stir at room temperature overnight. Add 30.0 mL of water and 30.0 mL of ethyl acetate to extract the reaction mixture. Separate the organic solvent layer, concentrate it, and purify the residue by silica gel column chromatography to obtain 11 (42.0 mg, 80.0%), with the eluent being petroleum ether / ethyl acetate (v / v = 10:1 - 5:1). Compound 12 can be prepared from compound 7 by reacting with allyl bromide under the same conditions, and the yields of these two steps are similar. The physicochemical data of compounds 11 and 12 are as follows:

[0083] Methyl (R)-6-(1-((tert-butyldimethylsilyl)oxy)ethyl)phenazine-1-carboxylate (11): Yellow solid, mp: 130 - 132 °C.1 1H NMR (600 MHz, CDCl 3 ) δ 8.43 (dd, J = 8.7, 1.3 Hz, 1H), 8.25 (dd, J = 6.9, 1.3 Hz, 1H), 8.21 (d, J = 8.7 Hz, 1H), 8.09 (d, J = 6.9 Hz, 1H), 7.89 (dd, J = 8.6, 7.0 Hz, 1H), 7.85 (dd, J = 8.7, 6.9 Hz, 1H), 6.21 (q, J = 6.2 Hz, 1H), 4.13 (s, 3H), 1.64 (d, J = 6.3 Hz, 3H), 0.98 (s, 9H), 0.15 (s, 3H), 0.05 (s, 3H). 13 13C NMR (150 MHz, CDCl 3 ) δ 167.3, 145.8, 143.5, 141.8, 140.7, 140.6, 133.9, 131.9, 131.3, 131.2, 128.6, 128.5, 126.7, 66.1, 52.7, 26.6, 26.0, 18.3, -4.7, -4.8. HRMS (ESI) calcd. for 22 C 28 H 2 N 3 O + Si + Na]

[0084] Allyl (R)-6-(1-((tert-butyldimethylsilyl)oxy)ethyl)phenazine-1-carboxylate (12): Yellow solid, mp: 140 - 142 °C. 1 1H NMR (600 MHz, CDCl 3 ) δ 8.45 - 8.42 (m, 1H), 8.29 - 8.26 (m, 1H), 8.20 (d, J = 8.6 Hz, 1H), 8.09 (d, J = 6.9 Hz, 1H), 7.89 (dd, J = 8.6, 7.0 Hz, 1H), 7.85 (dd, J = 8.6, 7.0 Hz, 1H), 6.22 (dd, J = 13.0, 6.7 Hz, 1H), 6.19 - 6.14 (m, 1H), 5.64 (dd, J = 17.2, 1.4 Hz, 1H), 5.39 (d, J = 10.5 Hz, 1H), 5.06 (d, J = 5.5 Hz, 2H), 1.64 (d, J = 6.3 Hz, 3H), 0.98 (s, 9H), 0.15 (s, 3H), 0.05 (s, 3H). 1313C NMR (150 MHz, CDCl 3 ) δ 166.5, 145.8, 143.6, 141.8, 140.7, 140.6, 134.0, 132.1, 131.9, 131.3, 131.2, 128.6, 128.5, 126.7, 118.5, 66.2, 66.1, 26.7, 26.0, 18.3, -4.7, -4.8. HRMS (ESI) calcd. for [C 24 H 30 N 2 O 3 Si + Na] + 445.1923, found 445.1925.

[0085] 9. Synthesis Scheme of Target Compound 13

[0086]

[0087] Compound 13 can be prepared by reacting Compound 12 with tetrabutylammonium fluoride under the same conditions as Compound 10, and the reaction yield is 90%. The physical and chemical data of Compound 13 are as follows:

[0088] Allyl (R)-6-(1-hydroxyethyl)phenazine-1-carboxylate (13): Yellow solid, mp: 110 - 112 °C. 1 1H NMR (600 MHz, CDCl 3 ) δ 8.40 (dd, J = 8.7, 1.0 Hz, 1H), 8.31 (dd, J = 6.9, 1.1 Hz, 1H), 8.25 (d, J = 8.7 Hz, 1H), 7.90 (dd, J = 8.6, 7.0 Hz, 1H), 7.85 (dd, J = 8.5, 6.9 Hz, 1H), 7.81 (d, J = 6.7 Hz, 1H), 6.17 (ddd, J = 22.6, 10.8, 5.6 Hz, 1H), 5.73 (q, J = 6.6 Hz, 1H), 5.63 (dd, J = 17.2, 1.3 Hz, 1H), 5.39 (dd, J = 10.5, 1.0 Hz, 1H), 5.06 (d, J = 5.5 Hz, 2H), 1.83 (d, J = 6.6 Hz, 3H). 13 13C NMR (150 MHz, CDCl 3) δ 166.2, 144.2, 142.5, 141.7, 140.8, 140.8, 133.3, 132.3, 132.0, 131.4, 130.9, 129.6, 129.3, 127.4, 118.6, 68.9, 66.3, 23.6. HRMS(ESI) calcd. for [C 18 H 16 N 2 O 3 +Na] + 331.1059, found 331.1052.

[0089] 10. Synthetic Scheme of Target Compound 14

[0090]

[0091] Compound 14 can be prepared by reacting Compound 10 with methyl iodide under the same conditions as Compound 11, and the reaction yield is 85%. The physical and chemical data of Compound 14 are as follows:

[0092] Methyl (R)-6-(1-hydroxyethyl)phenazine-1-carboxylate (14): Yellow solid, mp: 125 - 127 °C. 1 1H NMR (600 MHz, CDCl 3 ) δ 8.39 (dd, J = 8.7, 1.3 Hz, 1H), 8.29 (dd, J = 6.9, 1.3 Hz, 1H), 8.27 (dd, J = 8.8, 1.2 Hz, 1H), 7.90 (dd, J = 8.7, 6.9 Hz, 1H), 7.86 (dd, J = 8.6, 6.9 Hz, 1H), 7.81 (d, J = 6.7 Hz, 1H), 5.73 (q, J = 6.6 Hz, 1H), 4.14 (s, 3H), 1.83 (d, J = 6.6 Hz, 3H). 13 13C NMR (150 MHz, CDCl 3 ) δ 167.0, 144.2, 142.5, 141.7, 140.8 (2C), 133.3, 132.3, 131.3, 130.9, 129.7, 129.3, 127.4, 68.9, 52.8, 23.6. HRMS(ESI) calcd. for [C 16 H 14 N 2 O 3 +Na] + 305.0902, found 305.0904.

[0093] 11. Synthesis Scheme of Target Compound 15

[0094]

[0095] Place compound 10 (54.0 mg, 0.2 mmol) in a 25 mL single-necked flask, add 10 mL of dichloromethane, stir, then weigh sodium bicarbonate (84.0 mg, 1.0 mmol). At 0 °C, add Dess-Martin Periodinane (85.0 mg, 0.2 mmol). Remove the ice bath after 20 minutes and stir at room temperature for 2 hours. Detect the completion of the reaction by TLC. Add 30.0 mL of water and 30.0 mL of dichloromethane to extract the reaction solution, separate the organic solvent layer, concentrate it, and purify the extract by silica gel column chromatography to obtain 15 (42.0 mg, 78.0%), and the eluent is petroleum ether / ethyl acetate (v / v = 5:1). The physicochemical data of compound 15 are as follows:

[0096] 6-Acetylphenazine-1-carboxylic acid (15): Yellow solid, mp: 164 - 166 °C. 1 HNMR(600MHz,CDCl 3 )δ15.29(s,1H),9.05(dd,J=7.0,1.3Hz,1H),8.59(dd,J=8.7,1.3Hz,1H),8.45(dd,J=8.7,1.3Hz,1H),8.33(dd,J=6.9,1.3Hz,1H),8.12(dd,J=8.7,7.2Hz,1H),8.09(dd,J=8.7,7.2Hz,1H),3.11(s,3H). 13 C NMR(150MHz,CDCl 3 )δ200.6 165.6,142.9,141.6,139.9,139.5,139.4,138.2,135.3,132.5,132.4,131.6,131.0,125.0,33.0.HRMS(ESI)calcd.for[C 15 H 10 N 2 O 3 +Na] + 289.0589,found 289.0589.

[0097] 12. Synthesis Schemes of Target Compounds 16 and 17

[0098]

[0099] Compound 10 (54.0 mg, 0.2 mmol) was placed in a 25-mL single-necked flask, a magnetic stir bar was added, and anhydrous toluene (5.0 mL) was added. Sodium hydride (60%, 80.0 mg, 2.0 mmol) was weighed and added. At 0 °C, allyl bromide (120.0 mg, 1.0 mmol) was added dropwise. After 20 minutes, the ice bath was removed, and the mixture was stirred at room temperature for 2 hours. The reaction was monitored by TLC and found to be complete. 2 mL of methanol was added to quench the reaction, and then 30.0 mL of water and 30.0 mL of ethyl acetate were added to extract the reaction mixture. The organic layer was separated, concentrated, and the residue was purified by silica gel column chromatography to obtain 16 (12.0 mg, 20.0%) and 17 (8.0 mg, 12.0%). The eluent was petroleum ether / ethyl acetate (v / v = 10:1 - 5:1). The physicochemical data of compounds 16 and 17 are as follows:

[0100] (R)-6-(1-(allyloxy)ethyl)phenazine-1-carboxylic acid (16): Yellow solid, mp: 140 - 142 °C. 1 H NMR (600 MHz, CDCl 3 ) δ 15.67 (s, 1H), 9.00 (d, J = 7.0 Hz, 1H), 8.57 (d, J = 8.7 Hz, 1H), 8.21 (d, J = 8.7 Hz, 1H), 8.15 (d, J = 6.7 Hz, 1H), 8.09 - 8.03 (m, 2H), 6.08 - 6.00 (m, 1H), 5.96 (q, J = 6.4 Hz, 1H), 5.34 (dt, J = 7.7, 3.8 Hz, 1H), 5.23 (d, J = 10.4 Hz, 1H), 4.14 - 4.05 (m, 2H), 1.69 (d, J = 6.5 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 166.1, 143.9, 142.5, 142.2, 139.8, 139.8, 137.3, 135.4, 134.9, 133.5, 130.0, 127.4, 126.7, 124.8, 116.9, 71.9, 70.2, 23.7. HRMS (ESI) calcd. for [C 18 H 16 N 2 O 3 +Na] + 331.1059, found 331.1056.

[0101] Allyl (R)-6-(1-(allyloxy)ethyl)phenazine-1-carboxylate (17): Yellow solid, mp: 112 - 114 °C. 1H NMR (600 MHz, CDCl 3 ) δ 8.42 (dd, J=8.7, 1.3 Hz, 1H), 8.29 (dd, J=6.9, 1.3 Hz, 1H), 8.24 (dd, J=8.7, 1.0 Hz, 1H), 8.03 (d, J=6.8 Hz, 1H), 7.92 (dd, J=8.6, 7.0 Hz, 1H), 7.87 (dd, J=8.7, 6.9 Hz, 1H), 6.18 (ddd, J=22.7, 10.8, 5.5 Hz, 1H), 6.03 (ddd, J=22.6, 10.7, 5.5 Hz, 1H), 5.96 (q, J=6.4 Hz, 1H), 5.64 (dd, J=17.2, 1.5 Hz, 1H), 5.39 (dd, J=10.5, 1.3 Hz, 1H), 5.33 (dd, J=17.2, 1.6 Hz, 1H), 5.21 (dd, J=10.4, 1.4 Hz, 1H), 5.06 (d, J=5.5 Hz, 2H), 4.10 - 4.04 (m, 2H), 1.67 (d, J=6.5 Hz, 3H). HRMS (ESI) calcd. for [C 21 H 20 N 2 O 3 +Na] + 371.1372, found 371.1370.

[0102] 13. Synthetic Scheme of Target Compound 18

[0103]

[0104] Compound 10 (54.0 mg, 0.2 mmol) was placed in a 25 mL single-necked flask. 4-Dimethylaminopyridine (DMAP, 24.0 mg, 0.2 mmol) was weighed and a magnetic stir bar was added. The flask was evacuated, and then anhydrous THF (6.0 mL) and triethylamine (100.0 mg, 1.0 mmol) were added. At 0 °C, 2,4,6-trichlorobenzoyl chloride (150.0 mg, 0.6 mmol) was added dropwise. After 20 minutes, the ice bath was removed, and the mixture was stirred at room temperature overnight. 30.0 mL of water and 30.0 mL of ethyl acetate were added to extract the reaction mixture. The organic layer was separated, concentrated, and the residue was purified by silica gel column chromatography to obtain 18 (12.0 mg, 22.0%). The physicochemical data of compound 18 are as follows: 6-((R)-1-((6-((R)-1-hydroxyethyl)phenazine-1-carbonyl)oxy)ethyl)phenazine-1-carboxylic acid (18): Yellow solid, mp: 160 - 162 °C. 1 H NMR(600MHz,CDCl 3 )δ15.62(s,1H),9.03(d,J=7.0Hz,1H),8.66(d,J=8.6Hz,1H),8.58(d,J=6.9Hz,1H),8.44(d,J=8.7Hz,1H),8.37(d,J=6.4Hz,1H),8.29(d,J=8.6Hz,1H),8.21(d,J=8.5Hz,1H),8.10(t,J=7.8Hz,2H),7.97 - 7.92(m,1H),7.91 - 7.87(m,1H),7.84(d,J=6.5Hz,1H),7.69(q,J=6.4Hz,1H),5.76(dd,J=12.8,6.3Hz,1H),4.87(brs,1H),2.03(d,J=6.6Hz,3H),1.85(d,J=6.6Hz,3H). 13 CNMR(150MHz,CDCl 3 )δ166.2,166.0,144.2,142.8,142.6,142.0,141.8,141.5,140.9,140.8,139.9,139.8,137.6,135.6,133.4,133.1,132.4,131.7,131.1,130.3,129.4,129.2,127.8,127.4,127.3,124.8,69.9,68.8,23.7,22.7.HRMS(ESI)calcd.for[C 30 H 22 N4 O 5 +Na] + 541.1488, found 541.1489.

[0105] 14. Synthetic Scheme of Target Compound 19

[0106]

[0107] Compound 19 can be prepared from the reaction of Compound 18 with Dess-Martin periodinane under the same conditions as Compound 15, with a reaction yield of 84%. It can also be prepared by dissolving Compound 18 in dichloromethane and subjecting it to air oxidation (120 hours), with a yield of 10%. The physicochemical data of Compound 19 are as follows:

[0108] (R)-6-(1-((6-acetylphenazine-1-carbonyl)oxy)ethyl)phenazine-1-carboxylic acid (19): Yellow solid, mp: 169 - 171 °C. 1 H NMR (600 MHz, CDCl 3 ) δ 15.60 (s, 1H), 9.04 (dd, J = 7.1, 1.3 Hz, 1H), 8.67 (dd, J = 8.6, 1.3 Hz, 1H), 8.54 (d, J = 7.0 Hz, 1H), 8.49 - 8.46 (m, 1H), 8.45 - 8.42 (m, 1H), 8.41 (dd, J = 6.8, 1.1 Hz, 1H), 8.30 (d, J = 8.7 Hz, 1H), 8.27 (dd, J = 6.9, 1.2 Hz, 1H), 8.07 - 8.12 (m, 2H), 7.97 (dd, J = 8.3, 7.2 Hz, 2H), 7.71 (q, J = 6.5 Hz, 1H), 3.13 (s, 3H), 2.04 (d, J = 6.6 Hz, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 201.4, 166.0, 143.1, 142.6, 142.3, 141.9, 141.5, 141.0, 140.9, 140.0, 139.8, 139.3, 137.6, 135.6, 133.9, 133.8, 133.1, 132.9, 132.0, 131.7, 130.4, 130.3, 129.8, 127.7, 127.4, 124.8, 69.9, 33.0, 22.7. HRMS (ESI) calcd. for [C 30 H 20 N 4 O5 +Na] + 539.1331, found 539.1331.

[0109] Example 2 Antibacterial Activity Results of 19 Phenazinastatin Compounds

[0110] 1. Antibacterial Activity Test

[0111] Experimental Strains: Bacterium Methicillin resistant Staphylococcus aureus (MRSA, ATCC43300). The bacterial strain was inoculated and frozen in Tryptic Soy broth or agar (Tryptic Soy broth, TSB; Tryptic Soy Agar, TSA; BD Biosciences, San Jose, CA, USA) medium. Fungi Cryptococcus neoformans (ATCC 66031), Trichophyton mentagrophytes (ATCC 9533), Trichophyton rubrum (ATCC 28188). C. neoformans and T. mentagrophytes, T. rubrum were inoculated in Sabouraud dextrose broth medium (Sabouraud dextrose broth, SDB; Sabouraud dextrose agar, SDA; BD Biosciences, San Jose, CA, USA). All strains were inoculated into the corresponding liquid medium and stored frozen at -80 °C in the refrigerator for future use. Before each experiment, the strains were re-inoculated onto solid agar culture plates and subcultured at least once to revive the strains.

[0112] Experimental Instruments and Consumables: Microbial constant temperature incubator (IRM, Germany), ultra-low temperature refrigerator (-80 °C, Panasonic, Japan), laminar flow hood (ESCO, ESCO Singapore), bench-top constant temperature shaker (HNY-1008, Tianjin Ono Instruments Co., Ltd.), Eppendorf bench-top centrifuge (Eppendorf, Germany), Epoch microplate spectrophotometer (biotech, USA), bacterial culture plates (Guangzhou Jet Biotechnology Co., Ltd.).

[0113] Reagents: Tryptic Soy broth or agar (Tryptic Soy broth, TSB; Tryptic Soy Agar, TSA; BD Biosciences, San Jose, CA, USA), YM liquid medium (Yeast malt, YM; Yeast malt agar, YMA; BD Biosciences, San Jose, CA, USA), Sabouraud dextrose broth (Sabouraud dextrose broth, SDB; Sabouraud dextrose agar, SDA; BD Biosciences, San Jose, CA, USA).

[0114] Experimental method: Taking Candida albicans or Cryptococcus neoformans as examples, several monoclonal Candida albicans or Cryptococcus neoformans colonies were separately picked from the agar culture plate with a loop and inoculated into a sterile broth medium. The culture was carried out overnight at 30 °C and 200 rpm for activation. The bacterial liquid in the logarithmic growth phase was taken and diluted to an OD600 value between 0.03 - 0.06. Take the diluted bacterial liquid, add 195 μL per well to a 96-well plate, and then add 5 μL of the drug. Incubate for 24 hours (Cryptococcus neoformans is cultured for 48 hours), and read the value at the OD600 wavelength. Other bacteria are prepared and measured with reference to this method.

[0115]

[0116] Table 1. Test results of the antibacterial activity (inhibition rate) of compounds (concentration: 100 μg / mL)

[0117]

[0118] The activity test is the average value of the results of three experiments.

[0119] Experimental results and discussion: Compounds in the 3, 7, 10, 15, 18, 19 series have good antibacterial activity. Compounds 7 and 18 have the strongest activity, indicating that when the C-1 position of the right benzene ring is substituted by a carboxyl group among the derivatives substituted on the phenazine nucleus, it is beneficial to improve its antibacterial activity; when the hydrogen at the C-1' position of the ethyl group on the left benzene ring is substituted by a hydroxyl group or a hydroxy-silyl group, it is beneficial to improve its antibacterial activity. The inhibition rates of compounds 10, 13, 14, 18 against fungi reach more than 50%. Among them, compounds 13 and 14 have good antifungal activity, and compound 14 has the strongest activity, indicating that when the C-1 position of the right benzene ring is substituted by an ester and the hydrogen at the C-1' position of the ethyl group on the left benzene ring is substituted by a hydroxyl group among the derivatives substituted on the phenazine nucleus, it is beneficial to improve its antifungal activity.

[0120] Example 3. Antitumor activity test of 19 phenazine statin compounds

[0121] Taking human colon cancer cell line HCT-116, pancreatic cancer cell line HT-29, human prostate cancer cell line PANC-1, breast cancer cell line PC-3, liver cancer cell line Huh7, and liver cancer cell line HepG2 as examples

[0122] Experimental method:

[0123] Dissolve the compound samples in DMSO and culture the cells in RPMI1640 medium. Seed the tumor cells at a concentration of 2 - 7×10 4 cells / mL into 96-well plates and incubate them at 37°C and 5% CO 2 for 24 h. Then add 10 μL of the compound samples diluted with the medium, with the final concentration of each well being 20 μg / mL. Set up 3 replicate samples for each compound. Replace the compound with DMSO in the control group cells, and use three wells with only medium but no cells as background controls. After continuing the incubation for 72 h, fix the cells with 50% cold trichloroacetic acid solution and keep them at 4°C for 1 h. Wash off the fixing solution and air-dry. Add 100 μL of 1% glacial acetic acid solution containing 0.4% SRB, stain for 15 min, wash off the excess stain with 1% glacial acetic acid, and air-dry. Add 100 μL of 10 mM Tris buffer to dissolve and read the absorbance value (A) with a microplate reader at a wavelength of 515 nm.

[0124] Cell inhibition rate (%) = (average A value of the control wells without drug - average A value of the wells with drug) / average A value of the control wells without drug × 100%.

[0125] After the primary screening and re-screening of the compounds, finally, the compounds are diluted at 5 concentration gradients and added to the cultured cells respectively, and the tumor cell inhibition activity experiment is repeated. Measure the percentage inhibition rate at each concentration and calculate its half-maximal inhibitory concentration (IC 50 ) using the Bliss program.

[0126] Table 2. Effects of compounds on cancer cells (IC 50 , μM)

[0127]

[0128] The activity test is obtained by averaging the results of three experiments.

[0129] Experimental results and discussion: Compounds 2, 12, 18, and 19 have relatively good anti-cancer activities. Among them, compounds 18 and 19 have the best activities, indicating that the phenazine compound dimer is crucial for its anti-tumor activity. When the hydrogen at the ethyl C-1` position of the left benzene ring is replaced by a hydroxyl group, its anti-tumor activity is better than that of the carbonyl substitution.

Claims

1. A phenazinastatin compound represented by General Formula I, II or III, or a pharmaceutically acceptable salt thereof: Wherein, R 1 is H, OH, C1-C6 alkyl, C1-C6 alkoxy, COOR 5 , halogen; R 2 is H, TBS, C2-C6 alkenyl; R 3 is H, C1-C6 alkyl, C1-C6 alkoxy, halogen; R 4 is H, OH, C1-C6 alkyl, C1-C6 alkoxy, COOR 5 , halogen; R 5 is H, C1-C6 alkyl, C2-C6 alkenyl, unsubstituted or halogen-substituted phenyl, 2. A phenazinastatin compound represented by General Formula I, II or III, or a pharmaceutically acceptable salt thereof as claimed in claim 1: Wherein, R 1 is H, OH, C1-C4 alkyl, C1-C4 alkoxy, COOR 5 , halogen; R 2 is H, TBS, C2-C4 alkenyl; R 3 is H, C1-C4 alkyl, C1-C4 alkoxy, halogen; R 4 is H, OH, C1-C4 alkyl, C1-C4 alkoxy, COOR 5 , halogen; R 5 is H, C1-C4 alkyl, C2-C4 alkenyl, unsubstituted or halogen-substituted phenyl, 3. A phenazinastatin compound represented by General Formula I, II or III, or a pharmaceutically acceptable salt thereof as claimed in claim 1: Wherein, In General Formula I, R 1 is H, OH, C1-C4 alkyl, C1-C4 alkoxy, COOR 5 , bromine; R 2 is H, TBS, C2-C4 alkenyl; R 5 is H, C1-C4 alkyl, C2-C4 alkenyl, chlorine-substituted phenyl, In General Formula II, R 3 is H, C1-C4 alkoxy, bromine; In General Formula III, R 4 is H, OH, C1-C4 alkoxy, COOR 5 , bromine; R 5 is H or 4. A phenazinastatin compound or a pharmaceutically acceptable salt thereof as follows:

5. A method for preparing a phenazinastatin compound represented by General Formula I, II or III, or a pharmaceutically acceptable salt thereof as claimed in claim 1, Characterized in that, General Formula II is prepared by aniline and the corresponding nitrobenzene through a nucleophilic addition reaction and a reduction dehydration reaction; General Formula I is prepared on the basis of General Formula III through a keto group asymmetric reduction reaction and a protecting group reaction on the hydroxyl group, and General Formula III is obtained by oxidation on the basis of General Formula I or General Formula II.

6. A pharmaceutical composition comprising the phenazinastatin compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-4 and a pharmaceutically acceptable carrier or excipient.

7. Use of the phenazinastatin compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-4 or the pharmaceutical composition according to claim 6 in the preparation of an anti-tumor drug.

8. The use according to claim 7, Characterized in that, The tumor is colon cancer, pancreatic cancer, prostate cancer, breast cancer or liver cancer.

9. Use of the phenazinastatin compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-4 or the pharmaceutical composition according to claim 6 in the preparation of an antibacterial drug.

10. The use according to claim 9, Characterized in that, The antibacterial drug is an antibacterial or antifungal drug, and the bacteria are preferably methicillin-resistant Staphylococcus aureus; the fungi are preferably Trichophyton rubrum, Trichophyton mentagrophytes, Candida albicans or Cryptococcus neoformans.

Images