Harringtonine derivative and pharmaceutical composition, preparation method and application thereof

Abstract

The invention relates to a cephalotaxus fortunei ester derivative as well as a pharmaceutical composition, a preparation method and application thereof, and belongs to the field of pharmaceutical compounds. The cephalotaxus fortunei ester derivative and the pharmaceutical composition of the cephalotaxus fortunei ester derivative provided by the invention have excellent anti-tumor activity. In addition, the preparation method of the derivative also has the advantages of cheap and easily available raw materials, simplicity and convenience in operation and the like.

Description

Harringtonine derivatives and pharmaceutical compositions, preparation methods and uses thereof This application claims the priority of the prior invention patent application with application number 202211161020.8, entitled “Halringotrine derivatives and pharmaceutical compositions thereof, preparation methods and uses thereof”, filed by the applicant with the State Intellectual Property Office of China on September 22, 2022. The entire text of the prior application is incorporated herein by reference. Technical Field The invention relates to harringtonine derivatives and pharmaceutical compositions, preparation methods and uses thereof, and belongs to the field of pharmaceutical compounds. Background Art Harringtonine alkaloids such as Harringtonine 1 (HT), Homoharringtonine 2 (HHT), Deoxyharringtonine 3 (DHT) and Isoharringtonine 4 (IHT) are known anticancer drugs. Among them, homoharringtonine 2 was included in the Chinese Pharmacopoeia in 1990 for the clinical treatment of acute non-lymphocytic leukemia and has been in clinical use ever since. At present, the medicinal harrington alkaloids are separated from Torreya grandis plants, but natural harrington alkaloids only account for a small part of the total alkaloids and are mainly present in the non-renewable parts of the plants. In addition to being present in natural plant raw materials at low concentrations, harrington alkaloids are also mixed with many similar structures, so it is very difficult to separate high-purity harrington alkaloids from natural products. At the same time, due to the sharp decrease in the number of Torreya grandis plants, they have become rare protected plants, resulting in the separation of harrington alkaloids from plants that is far from meeting the needs of clinical application. The inventor's previously authorized Chinese patent ZL201510925650.1 reported a class of harringtonine alkaloid compounds, their synthesis methods and uses, among which some of the example compounds had certain inhibitory activity against HL-60 human leukemia cells. Currently, there is still a need to further study the derivatives of this type of compounds in order to develop active pharmaceutical compounds with improved anticancer activity. Summary of the invention In order to improve the above technical problems, the present invention provides a compound represented by formula (I), its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound: Among them, RS Selected from (R N ) m -G-(CH2) n -or (R Q ) m -G-(CH2) n -: R N represents a substituent containing a nitrogen atom, such as nitro, unsubstituted or optionally substituted with one, two or more R a Substituted with the following groups: -NR 6 R 7 、-NR 6’ -C(=YR 4 )-NR 6 R 7 ; Every R 6 , R 6’ and R 7 are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R b Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, R 10 C(=O)-、R 10 C(=O)O-、R 10 C(=O)NH-、R 10 OC(=O)-、R 10 NHC(=O)-、R 10 S(O)2-、R 10 S(O)2O-、R 10 OS(O)2-、R 10 S(O)-, three(C 1-20 Alkyloxy)silyl C 1-20 Alkyl, tri(C1-20 Alkyl)silyl; R Q represents H, halogen, -OH, -CN, unsubstituted or optionally substituted with one, two or more R c Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, R 10 C(=O)-、R 10 C(=O)O-、R 10 OC(=O)-、R 10 S(O)2-、R 10 S(O)2O-、R 10 OS(O)2-、R 10 S(O)-, three(C 1-20 Alkyloxy)silyl C 1-20 Alkyl, tri(C 1-20 Alkyl)silyl; G represents chemical bond, C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl; provided that when G is not a chemical bond, the positions on G substituted by different groups connected to G may be separated by 1-10 atoms, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 atoms; for example, when G is phenyl, the positions on G substituted by different groups connected to it may be separated by 1, 2, 3, 4 or 5 carbon atoms, for example, the different groups are substituted at the ortho position, meta position and / or para position on G, preferably meta position and / or para position; Each m is the same or different and is independently selected from an integer greater than 1; Each n is the same or different and is independently selected from an integer greater than 1; Each Y is the same or different and is independently selected from O, S or N, provided that when Y is selected from O or S, R 4 does not exist; R 1 and R 2 The same or different, independently selected from H, C 1-6 Alkyl or halogen; R 3 Selected from R 8 , R 8 -O-、R 8 -S-; R 4 is absent, or is selected from H, unsubstituted or optionally substituted with one, two or more R d Substituted with the following groups: R 8 -O-、R 8 -S-、R 9 C(=O)O-、R 10 OC(=O)O-、R 10 NHC(=O)-、R 10 NHC(=O)O-、R 10 C(=O)NH-; R 5 Select from H or C 1-6 alkyl; Every R a , R b , R c and R d are the same or different, independently selected from halogen, -OH, -CN, -NO2, oxo (=O), unsubstituted or optionally substituted by one, two or more R e Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20Arylthio, 5-20 membered heteroarylthio, R 11 C(=O)-、R 11 C(=O)O-、R 11 C(=O)NH-、R 11 OC(=O)-、R 11 NHC(=O)-、R 11 S(O)2-、R 11 S(O)2O-、R 11 OS(O)2-、R 11 S(O)-、-NR 12 R 13 、-NH-C(=Y)-NR 12 R 13 , three (C 1-20 Alkyloxy)silyl C 1-20 Alkyl, tri(C 1-20 Alkyl)silyl; Every R 8 , R 9 , R 10 and R 11 The same or different, independently selected from H, C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, R 11’ C(=O)-、R 11’ C(=O)O-、R 11’ C(=O)NH-、R 11’ OC(=O)-、R 11’ NHC(=O)-、R 11’ S(O)2-、R 11’ S(O)2O-、R 11’ OS(O)2-、R 11’ S(O)-、-NR 12 R 13 、-NH-C(=Y)-NR 12 R 13 , three (C 1-20 Alkyloxy)silyl C 1-20 Alkyl, tri(C 1-20 Alkyl)silyl; Every R 11’ , R 12 and R 13 are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R f Substituted with the following groups: C 1-20 Alkyl, C2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl; Every R e and R f are the same or different, independently selected from halogen, -OH, -CN, -NO2, -NH2, oxo (=O), unsubstituted or optionally substituted by one, two or more R g Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, R 14 C(=O)-、R 14 C(=O)O-、R 14 OC(=O)-、R 14 S(O)2-、R 14 S(O)2O-、R 14 OS(O)2-、R 14 S(O)-; Every R 14 The same or different, independently selected from C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl; Every R g are the same or different and are independently selected from halogen, -OH, -CN, -NO2, -NH2, oxo (=O), C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio; Optionally, the C 3-20 One, two or more carbon atoms of the cycloalkyl or 3-20 membered heterocyclic group may be optionally substituted with oxygen to form a carbonyl group. According to an embodiment of the present invention, G represents a chemical bond, C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, such as chemical bonds, C 1-8 Alkyl, C 2-8 Alkenyl, phenyl, naphthyl. According to an embodiment of the present invention, m represents an integer of 1 to 20, preferably an integer of 1 to 10, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. According to an embodiment of the present invention, n represents an integer of 1 to 20, preferably an integer of 1 to 10, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10. According to an embodiment of the present invention, halogen represents F, Cl, Br or I. According to an embodiment of the present invention, Y is selected from O, N or S. According to an embodiment of the present invention, R 3 Selected from H, C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, C 1-8 Alkyl-O-, C 2-8 Alkenyl-O-, C 3-15 Cycloalkyl-O-, C 3-15 Cycloalkenyl-O-, 3-15 membered heterocyclyl-O-, C 6-15 Aryl-O-, 5-15 membered heteroaryl-O-, C1-8 Alkyl-S-, C 2-8 Alkenyl-S-, C 3-15 Cycloalkyl-S-, C 3-15 Cycloalkenyl-S-, 3-15 membered heterocyclyl-S-, C 6-15 Aryl-S-, 5-15 membered heteroaryl-S-. According to an embodiment of the present invention, R 4 Not present or selected from H. According to an embodiment of the present invention, R N represents a substituent containing a nitrogen atom, such as nitro, unsubstituted or optionally substituted with one, two or more R a Substituted with the following groups: -NR 6 R 7 、-NH-C(=YR 4 )-NR 6 R 7 . According to an embodiment of the present invention, R N represents nitro, unsubstituted or optionally substituted with one, two or more R a Substituted with the following groups: -NR 6 R 7 、-NH-C(=YR 4 )-NR 6 R 7 , wherein Y is selected from O, N or S, R 4 Not present or selected from H. According to an embodiment of the present invention, R N Selected from -NR 6 R 7 、-NH-C(=O)-NR 6 R 7 、-NH-C(=S)-NR 6 R 7 or -NH-C(=NH)-NR 6 R 7 . Or according to an embodiment of the present invention, R N is selected from nitro, amino, or phenyl substituted by nitro or amino at the ortho, meta and / or para positions, wherein the amino group is unsubstituted or substituted by one, two or more selected from C 1-8 Alkylcarbonyl, C 1-8 Alkyloxycarbonyl, C 3-8 Cycloalkylcarbonyl, C 3-8 Cycloalkyloxycarbonyl, C 6-10 Arylcarbonyl, C 6-10 Aryloxycarbonyl, C 2-8 The substituents of the alkenyl group are substituted. According to an embodiment of the present invention, R 6 is selected from H, unsubstituted or optionally substituted with one, two or more R b Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, R 10 C(=O)-、R 10 C(=O)O-、R 10 OC(=O)-、R 10 S(O)2-、R 10 S(O)2O-、R 10 OS(O)2-、R 10 S(O)-, three(C 1-20 Alkyloxy)silyl C 1-20 Alkyl, tri(C 1-20 Alkyl)silyl;. According to an embodiment of the present invention, R 7 is selected from H, unsubstituted or optionally substituted with one, two or more R b Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, R 10 C(=O)-、R 10 C(=O)O-、R 10 OC(=O)-、R 10 S(O)2-、R 10 S(O)2O-、R 10 OS(O)2-、R 10 S(O)-, three(C 1-20 Alkyloxy)silyl C 1-20 Alkyl, tri(C 1-20 Alkyl)silyl. According to an embodiment of the present invention, R 7 is selected from H, unsubstituted or optionally substituted with one, two or more R b Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, R 10 C(=O)-、R 10C(=O)O-、R 10 OC(=O)-、R 10 S(O)2-、R 10 S(O)2O-、R 10 OS(O)2-、R 10 S(O)-, three(C 1-8 Alkyloxy)silyl C 1-8 Alkyl, tri(C 1-8 Alkyl)silyl. According to an embodiment of the present invention, R 10 Selected from C 1-8 Alkyl, C 2-8 Alkenyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, NH2. According to an embodiment of the present invention, each R a and R b are the same or different and are independently selected from halogen, -OH, -CN, -NO2, unsubstituted or optionally substituted by one, two or more R d Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, C 1-8 Alkyloxy, C 2-8 Alkenyloxy, C 3-15 Cycloalkyloxy, C 3-15 Cycloalkenyloxy, 3-15 membered heterocyclyloxy, C 6-15 Aryloxy, 5-15 membered heteroaryloxy, C 1-8 Alkylthio, C 2-8 Alkenylthio, C 3-15 Cycloalkylthio, C 3-15 Cycloalkenylthio, 3-15 membered heterocyclylthio, C 6-15 Arylthio, 5-15 membered heteroarylthio, R 11 C(=O)-、R 11 C(=O)O-、R 11 OC(=O)-、R 11 S(O)2-、R 11 S(O)2O-、R 11 OS(O)2-、R 11 S(O)-、-NR 12 R 13 、-NH-C(=Y)-NR 12 R13 ; Three (C 1-20 Alkyloxy)silyl C 1-20 alkyl; According to an exemplary embodiment of the present invention, R 7 selected from, for example, H, unsubstituted or optionally substituted with one, two or more R e Substituted with the following groups: C 1-8 Alkyl, C3-8 cycloalkyl, C 2-8 Alkenyl, tri(C 1-8 Alkyloxy)silyl C 1-8 Alkyl, phenyl, biphenyl, naphthyl. For example, R 7 is selected from H, unsubstituted or optionally substituted with one, two or more R e Substituted from the following groups: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, allyl, phenyl, According to an embodiment of the present invention, the compound represented by formula (I) can be selected from the compound represented by the following formula (I-1): Among them, R 7 , G, n, R 3 Independently selected from the definitions given above, Y represents O, S or NH. According to an embodiment of the present invention, R Q is selected from H, halogen, -OH, -CN, unsubstituted or optionally substituted with one, two or more R c Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, C 1-8 Alkyloxy, C 2-8 Alkenyloxy, C 3-15 Cycloalkyloxy, C 3-15 Cycloalkenyloxy, 3-15 membered heterocyclyloxy, C 6-15 Aryloxy, 5-15 membered heteroaryloxy, C 1-8 Alkylthio, C 2-8 Alkenylthio, C 3-15 Cycloalkylthio, C 3-15 Cycloalkenylthio, 3-15 membered heterocyclylthio, C 6-15 Arylthio, 5-15 membered heteroarylthio. According to an embodiment of the present invention, R Q is selected from H, halogen, -OH, -CN, unsubstituted or optionally substituted with one, two or more R c Substituted with the following groups: C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, for example unsubstituted or optionally substituted with one, two or more R c Substituted: methyl, ethyl, propyl, isopropyl, vinyl, propenyl, allyl, trifluoromethyl-methyl, pentafluoroethyl, phenyl, naphthyl, thienyl, dihydrobenzofuranyl. According to an exemplary embodiment of the present invention, R Q is selected from the above groups substituted by halogen or halogen. According to an embodiment of the present invention, R 3 Selected from H, C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, C 1-8 Alkyl-O-, C 2-8 Alkenyl-O-, C 3-15 Cycloalkyl-O-, C 3-15 Cycloalkenyl-O-, 3-15 membered heterocyclyl-O-, C 6-15 Aryl-O-, 5-15 membered heteroaryl-O-, C 1-8 Alkyl-S-, C 2-8 Alkenyl-S-, C 3-15 Cycloalkyl-S-, C 3-15 Cycloalkenyl-S-, 3-15 membered heterocyclyl-S-, C 6-15 Aryl-S-, 5-15 membered heteroaryl-S-. According to an exemplary embodiment of the present invention, R 3 Selected from H, methyl, methoxy, methylthio. According to an embodiment of the present invention, the compound represented by formula (I) can be selected from the compounds represented by the following formula (I-2), (I-4) or (I-5): Among them, R Q , G, n, R 3 are independently selected from the definitions given above. Among them, R 6 , R 7, G, n, R 3 Selected independently from the definitions given above; Among them, R 6 , R 10 , G, n, R 3 are independently selected from the definitions given above. According to an embodiment of the present invention, Y is selected from N. According to an embodiment of the present invention, R Q is selected from H, unsubstituted or optionally substituted with one, two or more R c Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl. According to an exemplary embodiment of the present invention, R Q is selected from unsubstituted or optionally substituted with one, two or more R c Substituted with the following groups: C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, for example unsubstituted or optionally substituted with one, two or more R c Substituted: methyl, ethyl, propyl, isopropyl, vinyl, propenyl, allyl, thienyl, dihydrobenzofuranyl. According to an embodiment of the present invention, R 3 Selected from H, C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl. According to an embodiment of the present invention, R 4 is selected from unsubstituted or optionally substituted with one, two or more R d Substituted with the following groups: R 8 -O-、R 8 -S-、R 9 C(=O)O-. According to an embodiment of the present invention, each R 8 and R 9 The same or different, independently selected from H, C 1-8 Alkyl, C 2-8 Alkenyl, C3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, -NR 12 R 13 ; According to an embodiment of the present invention, each R 12 and R 13 are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R f Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl. According to an embodiment of the present invention, R 12 Selected from H, R 13 is selected from unsubstituted or optionally substituted with one, two or more R f Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, -NR 12 R 13 , for example selected from cyclopentyl. According to an embodiment of the present invention, R 8 Selected from H, -OH, acryloyl, isobutyryl, isopentyl, According to an embodiment of the present invention, R 9 Selected from C 1-8 Alkyl, C 2-8 Alkenyl, NH2. According to an embodiment of the present invention, each R d are the same or different and are independently selected from halogen, -OH, -CN, -NO2, unsubstituted or optionally substituted by one, two or more R e Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, for example, selected from unsubstituted or optionally substituted by one, two or more R e The following groups substituted: phenyl, naphthyl,. According to an embodiment of the present invention, each Re are the same or different and are independently selected from halogen, -OH, -CN, -NO2, unsubstituted or optionally substituted by one, two or more R e Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, C 1-8 Alkyloxy, C 2-8 Alkenyloxy, C 3-15 Cycloalkyloxy, C 3-15 Cycloalkenyloxy, 3-15 membered heterocyclyloxy, C6- 15 Aryloxy, 5-15 membered heteroaryloxy, C 1-8 Alkylthio, C 2-8 Alkenylthio, C 3-15 Cycloalkylthio, C 3-15 Cycloalkenylthio, 3-15 membered heterocyclylthio, C 6-15 Arylthio, 5-15 membered heteroarylthio. According to an embodiment of the present invention, each R f the same or different, independently selected from halogen, -OH, -CN, -NO2, C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, C 1-8 Alkyloxy, C 2-8 Alkenyloxy, C 3-15 Cycloalkyloxy, C 3-15 Cycloalkenyloxy, 3-15 membered heterocyclyloxy, C 6-15 Aryloxy, 5-15 membered heteroaryloxy, C 1-8 Alkylthio, C 2-8 Alkenylthio, C 3-15 Cycloalkylthio, C 3-15 Cycloalkenylthio, 3-15 membered heterocyclylthio, C 6-15 Arylthio, 5-15 membered heteroarylthio. According to an embodiment of the present invention, the compound represented by formula (I) can be selected from the compound represented by the following formula (I-3): Among them, R Q , G, n, R 3 , R 4 are independently selected from the definitions given above. According to an exemplary embodiment of the present invention, the compound represented by formula (I) described above can be selected from the following compounds: Among them, the groups R, G, R 4 and n have the definitions described in the following table: According to an exemplary embodiment of the present invention, the compound represented by formula (I) described above can be selected from the following compounds: Among them, the groups R, R 3 and n have the definitions described in the following table: According to an exemplary embodiment of the present invention, the compound represented by formula (I) described above can be selected from the following compounds: Among them, the groups R, R 3 and R 8 Has the definitions described in the following table: Unless otherwise stated, although the definitions of the above-mentioned groups are used to describe the specific compound structures covered by the general formula compounds, those skilled in the art should understand that this specification also records the independent definition of each of the above-mentioned groups, and the independent definition can be used alone or together with other groups to further define one, two or more corresponding substituent groups in the general formula compounds, thereby further defining the general formula compounds. The present invention also provides a method for preparing the compound represented by formula (I), its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound, wherein the preparation method may include one selected from the following methods: Method (1) Among them, R 1 , R 2 , R 4 , R 5 , Y has the meaning given above; R 3 Selected from R 8 -O-; In step (1), a base and R 8 The reaction is carried out in the presence of -OH to prepare the compound of formula (I). Method (2) When the substituent R of the compound of formula (I) S When the amino group is contained, the corresponding nitro compound is used as a substrate to reduce and prepare the compound of formula (I). Preferably, the reduction is carried out in the presence of Zn and AcOH. Method (3) When the substituent R of the compound of formula (I) S When the acylamino group is contained, the compound of formula (I) can be prepared by acylation reaction using the corresponding amino compound as a substrate. Method (4) When the substituent R of the compound of formula (I) S When the urea group is contained, the corresponding amino compound is used as a substrate and reacted with an isocyanate compound to prepare the compound of formula (I). Methods (5) When the substituent R of the compound of formula (I) S When the guanidine group is contained, the corresponding amino compound is used as a substrate to react with nitrile amine, acyl nitrile amine or differently substituted carbodiimide compounds to prepare the compound of formula (I). Methods (6) Among them, R 1 , R 2 , R 3 , R 5 has the meaning given above; R 4 Selected from hydroxyl group; Y is selected from N; The step (1) is carried out in the presence of a base and hydroxylamine hydrochloride to prepare a compound of formula (I). Methods (7) Among them, R 1 , R 2 , R 3 , R 5 has the meaning given above; R 4 Selected from R 9 C(=O)O-; Y is selected from N; In step (1), a base and C 1-20 Alkyl-C(O)-OC(O)-C 1-20 The reaction is carried out in the presence of an alkyl group to prepare a compound of formula (I). Methods (8) Among them, R 1 , R 2 , R 3 , R 5 has the meaning given above; R 4 Selected from R 9 C(=O)O-; Y is selected from N; In step (1), a base and R 9 C(=O)Cl or R 9 The reaction is carried out in the presence of C(=O)OH to prepare the compound of formula (I). Methods (9) Among them, R 1 , R 2 , R 3 , R 5 has the meaning given above; R 4 Selected from R 8 -O-; R 8 Selected from C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl; Y is selected from N; In step (1), a base and R 8 -L to react to prepare a compound of formula (I); L is a leaving group, such as halogen, preferably Br or I. Methods (10) Among them, R 1 , R 2 , R 3 , R 5 has the meaning given above; R 4 Selected from R 10 NHC(=O)O-; Y is selected from N; The step (1) is performed in R 10 The reaction is carried out in the presence of -N=C=O to prepare the compound of formula (I). Optionally, the preparation method further comprises the step of reacting the prepared compound of formula (I) with a pharmaceutically acceptable acid or base to form a salt. The present invention also provides a pharmaceutical composition comprising at least one of the compound represented by formula (I), its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound thereof. The present invention also provides a pharmaceutical composition comprising a therapeutically effective amount of at least one of the compound represented by formula (I), its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound thereof. According to an embodiment of the present invention, the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipients. According to an embodiment of the present invention, the pharmaceutical composition may further contain one or more additional therapeutic agents. The present invention also provides the use of at least one of the compound represented by formula (I), its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound thereof in the preparation of a drug. According to an embodiment of the present invention, the compound represented by formula (I), its racemate, stereoisomer, tautomer, isotope label, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or its prodrug compound, the drug or the pharmaceutical composition is used to prevent and / or treat diseases caused by uncontrolled cell growth, proliferation and / or survival, inappropriate cellular immune response or inappropriate cellular inflammatory response, or diseases accompanied by uncontrolled cell growth, proliferation and / or survival, inappropriate cellular immune response or inappropriate cellular inflammatory response. In particular, the disease is, for example, a blood tumor, a solid tumor and / or their metastasis, such as leukemia and myelodysplastic syndrome, malignant lymphoma, head and neck tumors including brain tumors and brain metastases, chest tumors including non-small cell lung tumors and small cell lung tumors, gastrointestinal tumors, endocrine tumors, breast tumors and other gynecological tumors, urinary system tumors including kidney tumors, bladder tumors and prostate tumors, skin tumors and sarcomas, and / or their metastases. The present invention also provides the compound represented by formula (I), its racemate, stereoisomer, tautomer, isotope label, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound, the drug or the pharmaceutical composition for inhibiting tumor cells, wherein the tumor cells are selected from tumor cells of blood tumors and / or solid tumors, such as breast cancer cells, liver cancer cells, lung adenocarcinoma cells, leukemia cells, leukemia cell adriamycin-resistant strains, glioblastoma cells, cervical cancer cells, colon cancer cells and / or brain microvascular endothelial cells. The present invention also provides the compound represented by the formula (I), its racemate, stereoisomer, tautomer, isotope label, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or its prodrug compound, the use of the drug or the pharmaceutical composition in the preparation of a drug, the drug can be used to treat hyperproliferative disorders of mammals, or to inhibit, block, reduce, reduce cell proliferation and / or cell division and / or cause apoptosis. Hyperproliferative disorders include but are not limited to psoriasis, keloids and other hyperplasias affecting the skin, benign prostatic hyperplasia (BpH), solid tumors such as breast cancer, respiratory cancer, lung cancer, brain cancer, reproductive organ cancer, digestive tract cancer, urinary tract cancer, eye cancer, liver cancer, skin cancer, head and neck cancer, thyroid cancer, parathyroid cancer and their distal metastasis. The disease also includes lymphoma, sarcoma and leukemia. The drug can also be used to inhibit tumor cells, wherein the tumor cells are selected from tumor cells of blood tumors and / or solid tumors, such as breast cancer cells, liver cancer cells, lung adenocarcinoma cells, leukemia cells, leukemia cell adriamycin-resistant strains, glioblastoma cells, cervical cancer cells, colon cancer cells and / or brain microvascular endothelial cells. According to an embodiment of the present invention, examples of the tumor cells can be selected from at least one of human breast cancer cells MCF-7, liver cancer cells HepG2, lung adenocarcinoma cells A549, human leukemia cells HL-60, human leukemia cells adriamycin-resistant strain HL-60 / ADR, human glioblastoma cells U-87MG, human cervical cancer cells HeLa, human colon cancer cells HCT-116, human colon cancer cells Sw620, human colon cancer cells LoVo and human brain microvascular endothelial cells hCMEC / D3. As a drug, the compounds of the present invention can be administered in the form of a pharmaceutical composition. These compositions can be prepared in a manner well known in the pharmaceutical field, and they can be administered by a variety of routes, depending on whether local or systemic treatment is required and the area to be treated. It can be administered topically (e.g., transdermal, skin, eye and mucous membranes including intranasal, vaginal and rectal delivery), pulmonary (e.g., by inhalation or insufflation of powders or aerosols, including by nebulizers; intratracheal, intranasal), oral or parenteral. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; or intracranial, such as intrathecal or intraventricular administration. It can be administered parenterally in a single large dose form, or it can be administered by, for example, a continuous infusion pump. Topically administered pharmaceutical compositions and preparations can include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids, powder preparations and powders. Conventional pharmaceutical carriers, water, powder or oily bases, thickeners, etc. may be necessary or required. In preparing the compositions of the present invention, the active ingredient is usually mixed with an excipient, diluted by an excipient or enclosed in such a carrier in the form of a capsule, sachet, paper or other container. When the excipient serves as a diluent, it can be a solid, semisolid or liquid substance, which acts as a solvent, carrier or medium for the active ingredient. Thus, the composition can be in the form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols (solid or dissolved in a liquid medium); ointments containing, for example, up to 10% by weight of the active compound, soft and hard gelatin capsules, suppositories, sterile injectable solutions and sterile packaged powders. Some examples of suitable excipients include lactose, glucose, sucrose, sorbitol, mannitol, starch, gum arabic, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinyl pyrrolidone, cellulose, water, syrup and methylcellulose. The formulation may also contain: lubricants such as talc, sodium stearate, magnesium stearate, sodium oleate, sodium benzoate, sodium acetate, sodium chloride and mineral oil; wetting agents; emulsifying and suspending agents; preservatives such as methyl and hydroxypropyl benzoate; sweeteners and flavoring agents. The compositions of the invention can be formulated so as to provide quick, sustained or delayed release of the active ingredient after administration to the patient by employing procedures known in the art. The composition can be formulated in unit dosage form, each dose containing about 5 to 1000 mg, more usually about 100 to 500 mg of active ingredient. The term "unit dosage form" refers to physically discrete single dosage units suitable for use by human patients and other mammals, each unit containing a predetermined amount of active material calculated to produce the desired therapeutic effect in admixture with a suitable pharmaceutical excipient. The effective dosage range of the active compound can be very large, and is generally administered in a pharmaceutically effective amount. However, it is understood that the actual amount of compound administered is usually determined by the physician based on relevant circumstances, including the condition being treated, the route of administration selected, the actual compound being administered; the age, weight and response of the individual patient; the severity of the patient's symptoms, etc. For preparing solid compositions such as tablets, the main active ingredient is mixed with a pharmaceutical excipient to form a solid preformulation composition containing a homogeneous mixture of the compound of the invention. When these preformulation compositions are referred to as homogeneous, it is meant that the active ingredient is generally evenly distributed throughout the composition, so that the composition can be easily divided into equally effective unit dosage forms such as tablets, pills and capsules. The solid preformulation is then divided into unit dosage forms of the above type containing, for example, about 0.1 to 1000 mg of the active ingredient of the invention. The tablets or pills of the present invention may be coated or compounded to obtain dosage forms that provide the advantage of prolonged action. For example, the tablet or pill contains an inner dose and an outer dose component, the latter being a film-coated form of the former. The two components may be isolated by an enteric layer that is used to prevent disintegration in the stomach so that the inner component passes intact through the duodenum or is delayed in release. A variety of materials may be used for such enteric layers or coatings, including a variety of polymeric acids and mixtures of polymeric acids and such materials as shellac, cetyl alcohol, and cellulose acetate. Liquid forms in which the compounds and compositions of the present invention may be incorporated for oral or injectable administration include aqueous solutions, appropriately flavored syrups, aqueous or oil suspensions; and emulsions flavored with edible oils such as cottonseed oil, sesame oil, coconut oil or peanut oil; as well as elixirs and similar pharmaceutically acceptable vehicles. Compositions for inhalation or insufflation include solutions and suspensions, powders dissolved in pharmaceutically acceptable water or organic solvents or mixtures thereof. Liquid or solid compositions may contain suitable pharmaceutically acceptable excipients as described above. In certain embodiments, the composition is administered by oral or nasal respiratory route to achieve local or systemic effect. The composition may be atomized by using an inert gas. The atomized solution may be inhaled directly from an atomizing device, or the atomizing device may be connected to a mask curtain or an intermittent positive pressure breathing machine. Solutions, suspensions or powder compositions may be administered orally or by a device that delivers the formulation in an appropriate manner through the nose. The amount of compound or composition administered to a patient is not fixed and depends on the drug being administered, the purpose of administration, such as prevention or treatment; the patient's condition, the mode of administration, etc. In therapeutic applications, a patient already suffering from a disease may be administered a composition in an amount sufficient to cure or at least partially suppress the symptoms of the disease and its complications. The effective dose will depend on the disease state being treated and the judgment of the attending clinician, which depends on factors such as the severity of the disease, the patient's age, weight and general condition. The composition administered to the patient may be in the form of a pharmaceutical composition as described above. These compositions may be sterilized by conventional sterilization techniques or by filtration sterilization. The aqueous solution may be packaged for use as is, or lyophilized, and the lyophilized preparation may be mixed with a sterile aqueous carrier before administration. The pH of the compound preparation is generally 3 to 11, more preferably 5 to 9, and most preferably 7 to 8. It will be appreciated that the use of some of the aforementioned excipients, carriers or stabilizers may result in the formation of a pharmaceutical salt. The therapeutic dose of the compounds of the present invention may be determined, for example, based on the specific use of the treatment, the mode of administering the compound, the health and condition of the patient, and the judgment of the prescribing physician. The ratio or concentration of the compounds of the present invention in the pharmaceutical composition may not be fixed, depending on a variety of factors, including dosage, chemical properties (e.g., hydrophobicity), and route of administration. For example, the compounds of the present invention may be provided in a physiologically buffered aqueous solution containing about 0.1 to 10% (w / v) of the compound for parenteral administration. Some typical dosage ranges are about 1 μg / kg to about 1 g / kg body weight / day. In certain embodiments, the dosage range is about 0.01 mg / kg to about 100 mg / kg body weight / day. The dosage is likely to depend on such variables as the type and extent of the disease or condition, the general health status of the specific patient, the relative biological efficacy of the selected compound, the excipient formulation, and its route of administration. The effective dose can be obtained by extrapolation of a dose-response curve derived from an in vitro or animal model test system. The present invention provides the use of at least one of the compounds of formula (I), their racemates, stereoisomers, tautomers, isotope-labeled substances, N-oxides, hydrates, solvates, polymorphs, metabolites, pharmaceutically acceptable salts, pharmaceutically acceptable esters or prodrug compounds thereof in analytical tests for identifying compounds capable of inhibiting one or more tumor cells. More preferably, the competitive binding assay comprises contacting a compound according to the invention with tumor cells and detecting any changes in the interaction between the compound according to the invention and the tumor cells. Beneficial Effects The harringtonide derivatives and the pharmaceutical composition thereof provided by the present invention have excellent anti-tumor activity. In addition, the preparation method of the derivatives also has the advantages of cheap and readily available raw materials, simple operation and the like. Definition and explanation of terms Unless otherwise specified, the definitions of groups and terms recorded in the specification and claims of this application, including their definitions as examples, exemplary definitions, preferred definitions, definitions recorded in tables, definitions of specific compounds in examples, etc., can be arbitrarily combined and combined with each other. The definitions of groups and compound structures after such combinations and combinations should be understood to be within the scope of the specification and / or claims of this application. Unless otherwise specified, the numerical ranges described in this specification and claims are equivalent to describing at least each specific integer value therein. For example, the numerical range "1-10" is equivalent to describing each integer value in the numerical range "1-10", namely, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. In addition, when certain numerical ranges are defined as "numbers", it should be understood that the two endpoints of the range, each integer in the range, and the integers in the range are described. For example, "a number from 0 to 10" should be understood as not only recording each integer of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10, but also recording at least the sum of each of these integers and 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, respectively. It should be understood that herein, when describing one, two or more, "more" should refer to an integer greater than 2, for example, greater than or equal to 3, for example 3, 4, 5, 6, 7, 8, 9 or 10. The term "halogen" refers to fluorine, chlorine, bromine and iodine. The term "C 1-20 "Alkyl" is understood to mean a straight-chain or branched saturated monovalent hydrocarbon group having 1 to 20 carbon atoms. For example, "C 1-10 "Alkyl" means straight chain and branched chain alkyl groups having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. 1-8 The term “alkyl” refers to straight-chain and branched alkyl groups having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms. The alkyl group is, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl or 1,2-dimethylbutyl, or the like or isomers thereof. The term "C 2-20 "Alkenyl" is understood to mean preferably a linear or branched monovalent hydrocarbon radical containing one or more double bonds and having 2 to 20 carbon atoms, preferably "C 2-8 "C 2-8 "Alkenyl" is understood to mean preferably a linear or branched monovalent hydrocarbon radical which contains one or more double bonds and has 2, 3, 4, 5, 6, 7 or 8 carbon atoms, in particular 2 or 3 carbon atoms ("C 2-3"alkenyl"), it being understood that, in the case where the alkenyl contains more than one double bond, the double bonds may be separated from one another or conjugated. The alkenyl is, for example, vinyl, allyl, (E)-2-methylvinyl, (Z)-2-methylvinyl, (E)-but-2-enyl, (Z)-but-2-enyl, (E)-but-1-enyl, (Z)-but-1-enyl, pent-4-enyl, (E)-pent-3-enyl, (Z)-pent-3-enyl, -enyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)-pent-1-enyl, (Z)-pent-1-enyl, hex-5-enyl, (E)-hex-4-enyl, (Z)-hex-4-enyl, (E)-hex-3-enyl, (Z)-hex-3-enyl, (E)-hex-2-enyl, (Z)-hex-2-enyl, (E)-hex-1-enyl, (Z)-hex-1-enyl, isopropenyl, 2-hexenyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)-pent-1-enyl, (Z)-pent ...1-enyl, (Z)-pent-1-enyl, isopropenyl, 2-hexenyl, (E)-pent-2- -methylprop-2-enyl, 1-methylprop-2-enyl, 2-methylprop-1-enyl, (E)-1-methylprop-1-enyl, (Z)-1-methylprop-1-enyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, 1-methylbut-3-enyl, 3-methylbut-2-enyl, (E)-2-methylbut-2-enyl, (Z)-2-methylbut-2-enyl, (E)-1-methylbut-2-enyl 1-ethylprop-1-enyl, 1-propylvinyl, and 1-isopropylvinyl. The term "C 3-20 "Cycloalkyl" is understood to mean a saturated monovalent monocyclic, bicyclic (eg bridged, spiro) hydrocarbon ring or tricyclic alkane having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. 3-10 The cycloalkyl group may be a monocyclic hydrocarbon group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl or cyclodecyl, or a bicyclic hydrocarbon group such as borneol, indolyl, hexahydroindolyl, tetrahydronaphthyl, decahydronaphthyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptenyl, 6,6-dimethylbicyclo[3.1.1]heptyl, 2,6,6-trimethylbicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, 2,7-diazaspiro[3,5]nonanyl, 2,6-diazaspiro[3,4]octanyl, or a tricyclic hydrocarbon group such as adamantyl. The term "C 5-20 "Cycloalkenyl" is understood to mean a conjugated or non-conjugated monovalent monocyclic or bicyclic hydrocarbon ring with a degree of unsaturation of 1, 2 or 3, having 5 to 20 carbon atoms, preferably "C5-10 The term "C 5-10 "Cycloalkenyl" is understood to mean an unsaturated, monovalent monocyclic or bicyclic hydrocarbon ring having 5, 6, 7, 8, 9 or 10 carbon atoms. 5-10 The cycloalkenyl group may be a monocyclic hydrocarbon group, such as 3-cyclopentenyl, 1-cyclohexenyl, 2-cyclohexenyl, 2,4-cyclopentadienyl, 2,5-cyclohexadienyl or 1,3,5-cycloheptatrienyl or 1,3,6-cycloheptatrienyl, or a bicyclic hydrocarbon group such as hexahydronaphthalene ring or octahydronaphthalene ring. Unless otherwise specified, the term "C 5-20 The term "cycloalkenyl" includes all possible isomeric forms thereof, such as positional isomers or configurational isomers thereof. Unless otherwise defined, the term "3-20 membered heterocyclyl" refers to a saturated or unsaturated non-aromatic ring or ring system, for example, a 4-, 5-, 6- or 7-membered monocyclic ring, a 7-, 8-, 9- or 10-membered bicyclic ring (such as a fused ring, a bridged ring, a spirocyclic ring) or a 10-membered tricyclic ring system, and contains at least one, for example 1, 2, 3, 4, 5 or more heteroatoms selected from O, S and N, wherein N and S may also be optionally oxidized to various oxidation states to form nitrogen oxides, -S(O)- or -S(O)2- states. Preferably, the heterocyclyl may be selected from "3-10 membered heterocyclyl". The heterocyclyl may be connected to the rest of the molecule via any one of the carbon atoms or a nitrogen atom (if present). The heterocyclyl may include fused or bridged rings and spirocyclic rings. In particular, the heterocyclic group may include, but is not limited to, a 4-membered ring, such as azetidinyl, oxetanyl; a 5-membered ring, such as tetrahydrofuranyl, dioxolyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, pyrrolinyl; or a 6-membered ring, such as tetrahydropyranyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl or trithianyl; or a 7-membered ring, such as diazepanyl. Optionally, the heterocyclic group may be benzo-fused. The heterocyclic group may be bicyclic, such as, but not limited to, a 5,5-membered ring, such as a hexahydrocyclopenta [c] pyrrole-2 (1H) -yl ring, or a 5,6-membered bicyclic ring, such as a hexahydropyrrolo [1,2-a] pyrazine-2 (1H) -yl ring. The heterocyclic group may be partially unsaturated, i.e., it may contain one or more double bonds, such as but not limited to dihydrofuranyl, dihydropyranyl, 2,5-dihydro-1H-pyrrolyl, 4H-[1,3,4]thiadiazinyl, 4,5-dihydrooxazolyl or 4H-[1,4]thiazinyl, or it may be benzo-fused, such as but not limited to dihydroisoquinolinyl. When the 3-10 membered heterocyclic group is connected with other groups to form the compound of the present invention, it may be a carbon atom on the 3-10 membered heterocyclic group connected with other groups, or it may be a heterocyclic atom on the 3-10 membered heterocyclic group ring connected with other groups. For example, when the 3-10 membered heterocyclic group is selected from piperazinyl, it may be a nitrogen atom on the piperazinyl group connected with other groups. Or when the 3-10 membered heterocyclic group is selected from piperidinyl, it may be a nitrogen atom on the piperidinyl ring and a carbon atom on the para position thereof connected with other groups. The term "C 6-20 The term "aryl" is understood to mean preferably a monovalent aromatic or partially aromatic monocyclic or bicyclic (e.g. fused, bridged, spiro) hydrocarbon ring having 6 to 20 carbon atoms, which may be a single aromatic ring or a polyaromatic ring fused together, in particular a ring having 6 carbon atoms ("C6 aryl"), such as phenyl; or biphenyl, or a ring having 9 carbon atoms ("C9 aryl"), such as indanyl or indenyl, or a ring having 10 carbon atoms ("C 10 aryl”), such as naphthyl. When the C 6-10When the aryl group is substituted, it may be monosubstituted or polysubstituted. Also, there is no limitation on the substitution position, for example, it may be substituted at the ortho position, para position or meta position. The term "5-20 membered heteroaryl" is understood to include monovalent monocyclic, bicyclic (e.g., fused, bridged, spiro) or tricyclic aromatic ring systems having 5 to 10 ring atoms and containing 1 to 5 heteroatoms independently selected from N, O and S, preferably 1 to 3 heteroatoms independently selected from N, O and S and, in addition The outer radical in each instance may be benzo-fused. "Heteroaryl" also refers to a radical in which a heteroaromatic ring is fused to one or more aryl, alicyclic or heterocyclyl rings, wherein the radical or point of attachment is on the heteroaromatic ring. Non-limiting examples include 1-, 2-, 3-, 5-, 6-, 7-, or 8-indolizinyl, 1-, 3-, 4-, 5-, 6-, or 7-isoindolyl, 2-, 3-, 4-, 5-, 6-, or 7-indolyl, 2-, 3-, 4-, 5-, 6-, or 7-indazolyl, 2-, 4-, 5-, 6-, 7-, or 8-purinyl, 1-, 2-, 3-, 4-, 6-, 7-, 8-, or 9-quinolizinyl, 2-, 3-, 4-, 5-, 6-, 7-, or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7-, or 8-isoquinolyl, 1-, 4-, 5-, 6-, 7-, or 8-phthalazinyl. 1-, 2-, 3-, 4-, 5-, 6-, 7-, or 8-carbazolyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, or 8-carbozolyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, or 8-carbazolyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, or 8-carbozolyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, or 8-carbozolyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, or 8-carbozolyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, or 8-carbozolyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-, or 9-oxazolyl, 2-, 3-, 4-, 5-, 6-, 7-, 8-, or 9-oxazolyl, 2-, 3-, 4-, 5-, 6-, 7-, 8-, or 9-oxazolyl, 2-, 3-, 4-, 5-, 6-, 7-, 8-, or 9-oxazolyl, 2-, 3-, 4-, 5-, 6-, 7-, 8-, or 9-oxazolyl, 2-, 3-, 4-, 5-, 6-, 7-, 8-, or 9-oxazolyl, 5-, 6-, 7-, 8-, 9-, 10-, or 11-7H-pyrazino[2,3-c]carbazolyl, 2-, 3-, 5-, 6-, or 7-2H-furo[3,2-b]pyranyl, 2-, 3-, 4-, 5-, 7-, or 8-5H-pyrido[2,3-d]-oxazolyl, 1-, 3-, or 5-1H-pyrazolo[4,3-d]oxazolyl, 2-, 4-, or 54H-imidazo[4,5-d]thiazolyl, 3-, 5-, or 8-pyrazino[2,3-d]pyridazinyl, 2-, 3-, 5-, or 6-imidazo[2,1-b]thiazolyl, 1-, 3-, 6-, 7-, 8-, or 9-furo[3,4-c]cinnolinyl, 1-, 2-, 3-, 4-, 5-, 6-, 8-, 9-, 10 or 11-4H-pyrido[2,3-c]carbazolyl, 2-, 3-, 6- or 7-imidazo[1,2-b][1,2,4]triazinyl, 7-benzo[b]thienyl, 2-, 4-, 5-, 6- or 7-benzoxazolyl, 2-, 4-, 5-, 6- or 7-benzimidazolyl, 2-, 4-, 4-, 5-, 6- or 7-benzothiazolyl, 1-, 2-, 4-, 5-, 6-, 7-, 8- or 9-benzoxapinyl, 2-, 4-, 5-, 6-, 7- or 8-benzoxazinyl, 1-, 2-, 3-, 5-, 6-, 7-, 8-, 9-, 10- or 11-1H-pyrrolo[1,2-b][2]benzazapinyl. Typical fused heteroaryl groups include, but are not limited to, 2-, 3-, 4-, 5-, 6-, 7-, or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7-, or 8-isoquinolyl, 2-, 3-, 4-, 5-, 6-, or 7-indolyl, 2-, 3-, 4-, 5-, 6-, or 7-benzo[b]thienyl, 2-, 4-, 5-, 6-, or 7-benzoxazolyl, 2-, 4-, 5-, 6-, or 7-benzimidazolyl, and 2-, 4-, 5-, 6-, or 7-benzothiazolyl. When the 5-10 membered heteroaryl group is connected to other groups to form the compound of the present invention, the carbon atoms on the 5-10 membered heteroaryl ring may be connected to other groups, or the heteroatoms on the 5-10 membered heteroaryl ring may be connected to other groups. When the 5-10 membered heteroaryl group is substituted, it may be monosubstituted or polysubstituted. Furthermore, there is no limitation on the substitution site, for example, the hydrogen bonded to the carbon atom on the heteroaryl ring may be substituted, or the hydrogen bonded to the heteroatom on the heteroaryl ring may be substituted. The term "spirocyclic" refers to a ring system in which two rings share one ring-forming atom. The term "fused ring" refers to a ring system in which two rings share two ring atoms. The term "bridged ring" refers to a ring system in which two rings share three or more ring atoms. Unless otherwise specified, heterocyclic groups, heteroaryls or heteroarylene groups include all possible isomeric forms thereof, such as positional isomers thereof. Thus, for some illustrative non-limiting examples, forms substituted or bonded to other groups at one, two or more positions of the 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-positions, etc. (if present) may include pyridin-2-yl, pyridin-2-ylene, pyridin-3-yl, pyridin-3-ylene, pyridin-4-ylene and pyridin-4-ylene; thienyl or thienylene groups include thien-2-yl, thien-2-ylene, thien-3-ylene and thien-3-ylene; pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl. The term "oxo" means that a carbon atom, a nitrogen atom or a sulfur atom in a substituent is oxidized to form an oxy group (=O). Unless otherwise stated, the definitions of terms herein also apply to groups containing the term, e.g. 1-20 The definition of alkyl also applies to C 1-20 Alkyloxy and other terms. In the term "three (C 1-20 The term "tri(C 1-20 In the "alkyl)silyl" group, each C 1-20 The alkyl groups may be the same as or different from each other and are independently selected from the definitions given above. The abbreviations of the groups used herein have meanings well known in the art, for example, Me represents methyl, Et represents ethyl, Ph represents phenyl, TMS represents trimethylsilyl, i-Pr represents isopropyl, and Ac represents acetyl. Those skilled in the art will appreciate that the compounds of formula (I) may exist in the form of various pharmaceutically acceptable salts. If these compounds have a basic center, they may form acid addition salts; if these compounds have an acidic center, they may form a base addition salt; if these compounds contain both an acidic center (e.g., a carboxyl group) and a basic center (e.g., an amino group), they may also form an inner salt. The compounds of the present invention may exist in the form of solvates (e.g., hydrates), wherein the compounds of the present invention contain a polar solvent as a structural element of the crystal lattice of the compound, in particular water, methanol or ethanol. The amount of the polar solvent, in particular water, may be present in a stoichiometric or non-stoichiometric ratio. The compounds of the present invention may exist in the form of stereoisomers, which may be enantiomers and cis-trans isomers, or enantiomers and diastereomers. According to its molecular structure, the compounds of the present invention may be chiral, and therefore various enantiomeric forms may exist. Thus, these compounds may exist in racemic form or optically active form. The compounds of the present invention encompass isomers or mixtures, racemates in which each chiral carbon is in R or S configuration. The compounds of the present invention or their intermediates can be separated into enantiomeric compounds by chemical or physical methods known to those skilled in the art, or used in this form for synthesis. In the case of racemic amines, diastereomers are prepared from the mixture by reaction with an optically active resolution agent. Examples of suitable resolution agents are optically active acids, such as tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid, suitable N-protected amino acids (e.g., N-benzoylproline or N-phenylsulfonylproline) or various optically active camphorsulfonic acids in R and S forms. Chromatographic enantiomer resolution can also be advantageously carried out with the aid of optically active resolving agents such as dinitrobenzoylphenylglycine, cellulose triacetate or other carbohydrate derivatives or chiral derivatized methacrylate polymers immobilized on silica gel. Suitable eluents for this purpose are aqueous or alcoholic solvent mixtures, for example, hexane / isopropanol / acetonitrile. The term "cis-trans isomers" means isomers that differ in the orientation of substituent atoms relative to a carbon-carbon double bond. Substituent atoms (not H) on either side of a carbon-carbon double bond may be in the E or Z configuration. In the "E" (opposite) or "chair" configuration, the substituents are on opposite sides relative to the carbon-carbon double bond; in the "Z" (same side) or "boat" configuration, the substituents are oriented on the same side relative to the carbon-carbon double bond. Compounds having a mixture of "cis" and "trans" species are designated "cis / trans". As described herein, the symbols "R", "S", "E", "Z", "cis", "trans", etc. are used to indicate the atomic configuration relative to the core molecule and as defined in IUPAC Recommendations for Fundamental Stereochemistry (Section E)), Pure Appl. Chem., 1976, 45: 13-30. Individual isomers of the compounds of the invention can be prepared by either isomer-specific synthesis or by resolution of isomeric mixtures. Conventional resolution techniques include the use of optically active salts to form the free bases of each isomer of an isomeric pair (followed by fractional crystallization and free base regeneration), the formation of esters or amides of each isomer of an isomeric pair (followed by chromatographic separation and removal of the chiral auxiliary), or the use of preparative TLC (thin layer chromatography) or chiral HPLC columns to resolve isomeric mixtures of either starting materials or final products. The term "patient" refers to any animal including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, pigs, cows, sheep, horses or primates, and most preferably humans. The term "therapeutically effective amount" refers to the amount of an active compound or drug that elicits a biological or medical response that a researcher, veterinarian, physician or other clinician is seeking in a tissue, system, animal, individual or human, and includes one or more of the following: (1) Preventing disease: for example, preventing a disease, disorder or condition in an individual who is susceptible to the disease, disorder or condition but has not yet experienced or developed the pathology or symptoms of the disease. (2) Suppressing disease: for example, suppressing a disease, disorder or condition in an individual who is experiencing or developing the pathology or symptoms of the disease, disorder or condition (i.e., preventing further development of the pathology and / or symptoms). (3) Alleviating disease: for example, alleviating a disease, disorder or condition in an individual who is experiencing or developing the pathology or symptoms of the disease, disorder or condition (i.e., reversing the pathology and / or symptoms). The therapeutically effective amount can be initially estimated from cell culture assays, and initial doses can also be estimated from in vivo data. Using these preliminary guidelines, one of ordinary skill in the art can determine effective doses for humans. In addition, the toxicity and therapeutic efficacy of the compounds described herein can also be determined by standard pharmaceutical procedures in cell cultures or experimental animals, for example, by determining the LD 50 and ED 50 . Examples of the "excipients" referred to in the present invention are given in "Handbook of Pharmaceutical Excipients, 2nd edition, 1994, edited by A Wade and PJ Weller". The "carrier" or "diluent" of the present invention is well known in the pharmaceutical art and is described in, for example, Remington's Pharmaceutical Sciences, Mack Publishing Co. (AR Gennaro ed. 1985). The choice of pharmaceutical carrier, adjuvant or diluent can be selected according to the expected route of administration and standard pharmaceutical practice. The pharmaceutical composition may contain or additionally contain any suitable adhesive, lubricant, suspending agent, coating agent, solubilizer, buffer, flavoring agent, surfactant, thickener, preservative (including antioxidant) etc. as a carrier, adjuvant or diluent, and the material contained in order to make the preparation isotonic with the blood of the recipient. Pharmaceutical formulations suitable for oral administration in which the carrier is a solid are most preferably in the form of unit dose formulations, such as pills, capsules or tablets each containing a predetermined amount of active compound. Tablets can be prepared by compression or molding, optionally with one or more auxiliary ingredients. Compressed tablets can be prepared by compressing the active compound in a free-flowing form (such as a powder or granules) in a suitable machine, optionally mixed with a binder, lubricant, inert diluent, lubricating substance, surfactant or dispersant. Molded tablets can be prepared by molding the active compound and an inert liquid diluent. The tablets can be optionally coated, and if not coated, symbols can be optionally printed. Capsules can be prepared by filling the active compound alone or mixed with one or more auxiliary ingredients into a capsule shell and then sealing in a conventional manner. Cachets are similar to capsules, in which the active compound is sealed in a rice paper film together with any auxiliary ingredients. The active compound can also be formulated as dispersible particles, for example, which can be suspended in water or sprinkled on food before administration. The particles can be packaged in, for example, sachets. Formulations suitable for oral administration wherein the carrier is a liquid may be presented as a solution or suspension in an aqueous or non-aqueous liquid, or as an oil-in-water liquid emulsion. The term "pharmaceutically acceptable salt" includes suitable acid addition salts or base salts thereof. For suitable pharmaceutical salts, see J Pharm Sci, 66, 199, 1977, Berge et al. The term "pharmaceutically acceptable ester" refers to esters formed with esterifiable functional groups in the structure of the compounds of the present invention using organic acids or alcohols / hydroxides. The term "isotopically labeled" means that at least one atom in the compound of the present invention is replaced by an isotope. Examples of such isotopes include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine and chlorine, such as the corresponding 2 H. 3 H. 13 C. 14 C. 15 N. 17 O. 18 O. 31 P. 32 P. 35 S. 18 F and 36 Cl. Use isotopes such as deuterium (i.e. 2 H) substitution may provide certain therapeutic advantages resulting from greater metabolic stability, such as increased in vivo half-life or reduced dosage requirements, and therefore may be preferred in certain circumstances. For example, the present invention includes compounds of formula (I) in which any hydrogen atom is replaced by a deuterium atom. The term "prodrug compound" refers to a covalently bonded compound that releases the active parent drug according to formula (I) in vivo. Such prodrugs are generally compounds of the invention in which one or more appropriate groups have been modified so that the modification may be reversed after administration to a human or mammalian subject. Reversal is usually performed by enzymes naturally present in such subjects, although a second agent may be administered with the prodrug for reversal in vivo. Examples of such modifications include pharmaceutically acceptable esters as described above, where such reversal may be performed by esterases and the like. The term "polymorph" refers to various crystalline forms, polymorphic forms and hydrated forms of the compounds of the present invention. It is well known in the pharmaceutical industry that chemical compounds can be isolated in any of these forms by purification and / or separation of solvents used in the synthetic preparation of such compounds. The term "administration" means that the pharmaceutical composition of the present invention is suitable for rectal, intranasal, intrabronchial, topical (including oral and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous, intraarterial and intradermal), intraperitoneal or intrathecal administration. Preferably, the preparation is a preparation for oral administration. The preparation can be conveniently presented in a unit dosage form, i.e., in the form of discrete portions containing a unit dose or a plurality of units or subunits of a unit dose. As an example, the preparation can be in the form of tablets and sustained-release capsules, and can be prepared by any method known in the pharmaceutical field. The formulations of the present invention for oral administration may be presented as discrete units such as capsules, gels, drops, cachets, pills or tablets each containing a predetermined amount of active agent; as a powder or granules; as a solution, emulsion or suspension of the active agent in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion; or as a bolus formulation, etc. Preferably, each dose of these compositions contains 1 to 250 mg and more preferably 10-100 mg of active ingredient. For compositions for oral administration (e.g., tablets and capsules), solvents and / or common excipients are also included, such as binders, such as syrup, gum arabic, gelatin, sorbitol, tragacanth, polyvinylpyrrolidone (povidone), methylcellulose, ethylcellulose, sodium carboxymethylcellulose, hydroxypropylmethylcellulose, sucrose and starch; fillers and carriers, such as corn starch, gelatin, lactose, sucrose, microcrystalline cellulose, kaolin, mannitol, dicalcium phosphate, sodium chloride and alginic acid; and lubricants, such as magnesium stearate, sodium stearate and other metal stearates, glycerol stearate, stearic acid, silicone fluid, talcum wax, oil and colloidal silicon dioxide. Flavoring agents such as peppermint, wintergreen oil, cherry flavor, etc. may also be used. It may be necessary to add a colorant to make the dosage form easily recognizable. Tablets may also be coated by methods well known in the art. Other formulations suitable for oral administration include lozenges containing the active agent in a flavored basis, usually sucrose and acacia or tragacanth; pastilles containing the active agent in an inert basis such as gelatin and glycerin, or sucrose and acacia; and mouthwashes containing the active agent in a suitable liquid carrier. Other forms of administration include solutions or emulsions prepared by intravenous, intraarterial, intrathecal, subcutaneous, intradermal, intraperitoneal or intramuscular injection and made from sterile or sterilizable solutions. Injectable forms usually contain between 10-1000 mg, preferably between 10-250 mg, of active ingredient per dose. The administration form can also be combined administration, that is, one or more compounds of the present invention are administered in combination with one or more other active agents. In this case, the compounds of the present invention and one or more other active agents can be administered continuously, simultaneously or sequentially. DETAILED DESCRIPTION The technical scheme of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect. Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods. Analytical methods The spectrometer was used to measure the spectroscopy results in the solvents described at room temperature. 1 H nuclear magnetic resonance (NMR) spectra unless otherwise indicated. In all cases, the NMR data are consistent with the proposed structure. The characteristic chemical shift (δ) is given in parts per million using conventional abbreviations for designating major peaks: for example, s, singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublets; br, broad. Mass spectra were recorded using an Agilent 1290 Infinity / 6460 triple Quad LCMS. When thin layer chromatography (TLC) was used, it refers to silica gel TLC. Example 1: Synthesis of harringtonine analogs containing nitro-substituted benzene rings Step 1.1 Preparation of compound 5 Under argon protection, p-nitrophenylpropionaldehyde (0.18 g, 1 mmol), NC·TMS (0.12 g, 1.2 mmol), IMESCL (0.03 g, 0.1 mmol) were dissolved in THF (5 mL), and t-BuOK (0.01 g, 0.1 mmol) was added under stirring at room temperature and reacted at room temperature for 5 min. After the reaction was completed by monitoring on a TLC plate, the mixture was concentrated, quenched by adding EtOAc (10 mL) and 2M HCl (5 mL), separated, extracted with EtOAc (2×10 mL), and the organic phases were combined, washed with sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated. Column separation PE:EA=4:1. Compound 5: light yellow liquid, 1.90 g, yield 94%. 1 H NMR (400MHz, CDCl3) δ8.17(d,J=8.3Hz,2H),7.38(d,J=8.3Hz,2H),4.49(t,J=6.5H z,1H),3.26(s,1H),2.97(t,J=7.8Hz,2H),2.20(ddd,J=11.4,8.9,5.6Hz,2H)ppm. Same as step 1.1, except that m-nitrophenylpropionaldehyde and 3-nitrophenylpropionaldehyde were used instead of p-nitrophenylpropionaldehyde to obtain the following compounds 6 and 7, respectively: Compound 6: light yellow liquid, 8.10 g, yield 94%. 1 H NMR (400MHz, CDCl3) δ8.11 (dd, J=7.6, 1.4Hz, 2H), 7.56 (dt, J=7.7, 1.5Hz, 1H), 7.50 (td ,J=7.5,1.1Hz,1H),4.51(t,J=6.5Hz,1H),2.98(t,J=7.8Hz,2H),2.30–2.15(m,2H)ppm. Compound 7: colorless liquid, 7.2 g, yield 79%. 1 H NMR (400MHz, CDCl3) δ4.75–4.61(m,2H),4.61–4.51(m,1H),2.64–2.54(m,1H),2.53–2.42(m,1H)ppm. Step 1.2 Preparation of compound 8 General operation: Under argon protection, compound 5 (1.90 g, 9.21 mmol) was dissolved in CH3OH (30 mL) solution, concentrated HCl (6.5 mL) was added, and the mixture was heated to 80°C and refluxed for about overnight. After the reaction was completed by TLC plate monitoring, it was cooled to room temperature, concentrated, and EtOAc (20 mL) and H2O were added for quenching. The liquids were separated, extracted with EtOAc (2×20 mL), and the organic phases were combined, washed with sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated. Compound 8

[0035] : Pale yellow liquid, 2.15g, yield 98%. 1 H NMR (400MHz, CDCl3) δ8.15(d,J=8.7Hz,2H),7.37(d,J=8.8Hz,2H),4.19(dd,J=8.1,3.8Hz,1H),3.77(s,3H),2.97–2.76(m,2H),2.24–2.08(m,2H)ppm. Same as step 1.2, except that raw material 5 is replaced by 6 and 7, and compounds 9 and 10 can be prepared respectively: Compound 9: light yellow liquid, 9.38 g, yield 98%. 1 H NMR (400MHz, CDCl3) δ8.11–8.02(m,2H),7.55(d,J=7.5Hz,1H),7.45(t,J=7.8Hz,1H),4.19(dd,J=8.0,3. 9Hz,1H),3.77(s,3H),2.97–2.79(m,2H),2.16(dddd,J=13.7,9.7,7.2,3.9Hz,1H),2.06–1.92(m,1H)ppm. Compound 10: no yellow liquid, 6.7 g, yield 60%. 1 H NMR (400MHz, CDCl3) δ4.63–4.47(m,2H),4.31(dd,J=8.7,4.1Hz,1H),3.82(s,3H),2.58(ddd,J=14.6,11.5,7.2Hz,1H),2.27(dt,J=14.8,7.6Hz,1H)ppm. Step 1.3 Preparation of compound 11 Compound 8 (2.15 g, 9.00 mmol) was dissolved in CH2Cl2 (80 mL) solution, and Dess-Martin (11.45 g, 27.0 mmol) was added, and the reaction was allowed to proceed overnight at room temperature. After the reaction was completed by monitoring on a TLC plate, saturated sodium bicarbonate solution and saturated sodium thiosulfate solution (1:1) were added to quench, the mixture was separated, and the mixture was extracted with CH2Cl2 (2×40 mL). The organic phases were combined, washed with sodium bicarbonate solution, washed with sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated. Column separation: PE:EA=4:1. Compound 11: light yellow liquid, 1.37 g, yield 64%. 1 H NMR (400MHz, CDCl3) δ8.15 (d, J = 8.7Hz, 2H), 7.38 (d, J = 8.7Hz, 2H), 3.87 (s, 3H), 3.24 (t, J = 7.1Hz, 2H), 3.07 (t, J = 7.3Hz, 2H) ppm. Same as step 1.3, except that raw material 8 is replaced by 9 and 10, and compounds 12 and 13 can be prepared respectively: Compound 12: light yellow liquid, 6.82 g, yield 73%. 1 H NMR (400MHz, CDCl3) δ8.08 (dd, J=7.5, 1.4Hz, 2H), 7.56 (d, J=7.6Hz, 1H), 7.47 ( t,J=8.1Hz,1H),3.87(s,3H),3.26(t,J=7.3Hz,2H),3.08(t,J=7.3Hz,2H)ppm. Compound 13: colorless liquid, 4.5 g, yield 68%. 1 H NMR (400MHz, CDCl3) δ4.73 (t, J = 5.9 Hz, 2H), 3.93 (s, 3H), 3.53 (t, J = 5.9 Hz, 2H) ppm. Step 1.4 Preparation of compound 14 General operation: Add a solution of p-nitrobenzene ring side chain ketoester 11 (2.00 g, 8.40 mmol) in CH3OH (2 mL) dropwise to a 2M NaOH (0.67 g, 16.80 mmol) aqueous solution at room temperature and react at room temperature (about 2 h). After the reaction is complete as monitored by TLC plate, concentrate (to remove methanol), add Et2O (10 mL), separate the liquids, quench the aqueous phase with 2M HCl (10 mL), adjust to pH <1, extract with Et2O (3×10 mL), combine the organic phases, wash with sodium chloride solution, dry over anhydrous sodium sulfate, filter and concentrate. Compound 14

[0036] : Pale yellow liquid, 1.00g, yield 99%. 1 H NMR (400MHz, CDCl3) δ8.15 (d, J = 8.7Hz, 2H), 7.39 (d, J = 8.8Hz, 2H), 3.31 (t, J = 7.3Hz, 2H), 3.09 (t, J = 7.2Hz, 2H) ppm. Same as step 1.4, except that raw material 11 is replaced by 12 and 13, and compounds 15 and 16 can be prepared respectively: Compound 15: light yellow liquid, 1.00 g, yield 99%. 1 H NMR (400MHz, CDCl3) δ8.13–8.07(m,2H),7.56(d,J=7.6Hz,1H),7.51–7.46(m,1H),3.36(t,J=7.3Hz,2H),3.11(t,J=7.3Hz,2H)ppm. Compound 16: colorless liquid 4.3 g, yield 96%. 1 H NMR (400MHz, CDCl3) δ4.66 (t, J = 5.9 Hz, 2H), 3.48 (t, J = 5.9 Hz, 2H) ppm. Step 1.5 Preparation of compound 17 General procedure: Under argon protection, DMF (0.01 g, 0.02 mmol) and oxalyl chloride (0.25 g, 2.0 mmol) were added dropwise to a solution of p-nitrophenyl side chain α-keto acid 14 (0.23 g, 1 mmol) in CH2Cl2 (10 mL) at 0°C. The mixture was moved to room temperature and reacted overnight. After the reaction was completed as monitored by TLC plate, the mixture was concentrated. The crude product was obtained and used directly in the next step without further purification. Under argon protection, CET (0.16 g, 0.5 mmol) was dissolved in pyridine (1 mL) and CH2Cl2 (5 mL) solution, and the above generated p-nitrophenyl side chain ketoacid chloride (0.48 g, 2.00 mmol) in CH2Cl2 (5 mL) solution was added dropwise at 0°C, and the reaction was allowed to proceed overnight at 0°C. The mixture was heated to room temperature, washed with a large amount of water, separated, extracted with CH2Cl2 (2×10 mL), and the organic phases were combined, washed with sodium bicarbonate solution and sodium chloride solution, respectively, and dried over anhydrous sodium sulfate. The mixture was filtered, concentrated, and separated by gradient column (CH2Cl2:Et2O=200:1~100:1). Compound 17: pale yellow amorphous solid, 552 mg, yield 26%. 1H NMR (400MHz, CDCl3) δ8.12(d,J=8.5Hz,2H),7.24(d,J=8.7Hz,2H),6.56(s,1H),6.45(s,1H),5.88(d,J=9.3 Hz,1H),5.80(s,1H),5.75(s,1H),5.11(s,1H),3.82(d,J=9.4Hz,1H),3.70(s,3H),3.21–3.09(m,1H),3.10– 3.02(m,2H),2.94–2.85(m,1H),2.81(t,J=7.3Hz,2H),2.65(dt,J=7.2,3.1Hz,1H),2.61–2.54(m,2H),2.30( dd,J=14.6,7.0Hz,1H),2.00(dd,J=8.4,3.5Hz,1H),1.94–1.86(m,1H),1.78–1.71(m,2H)ppm.HRMS(ESI)m / z calcd for C 28 H 29 N2O8,[M+H] + 521.1918, found 521.1945. Same as step 1.5, except that raw material 14 is replaced by 15 and 16, to prepare compounds 18 and 19 respectively: Compound 18: pale yellow amorphous solid, 3.916 g, yield 52%. 1 H NMR (400MHz, CDCl3) δ7.89(dt,J=6.6,2.5Hz,1H),7.80(s,1H),7.27(d,J=6.5Hz,2H),6.38(s,1H),6.24(s,1H),5. 71(d,J=9.2Hz,1H),5.60(d,J=1.4Hz,1H),5.55(d,J=1.4Hz,1H),4.93(s,1H),3.65(d,J=9.4Hz,1H),3.53(s,3H),3 .03–2.94(m,1H),2.92–2.87(m,1H),2.75–2.70(m,1H),2.64(t,J=7.3Hz,2H),2.48–2.38(m,4H),2.14(dd,J=14.5 ,7.0Hz,1H),1.88–1.81(m,1H),1.72(ddd,J=12.2,7.6,4.6Hz,1H),1.57(dd,J=11.1,5.7Hz,2H)ppm.HRMS(ESI)m / z calcd for C 28 H 29N2O8,[M+H] + 521.1918, found 521.1919. Compound 19: light yellow amorphous solid, 2.84 g, yield 67%. HRMS (ESI) m / z calculated for C 22 H 25 N2O8,[M+H] + 445.1605, found 445.1610. Step 1.6 Preparation of compound 20 General procedure: Under argon protection, add boron trifluoride etherate (0.57 g, 4 mmol) dropwise to a solution of α-ketoacetyl ester of 17 (0.52 g, 1 mmol) in CH2Cl2 (10 mL) at 0°C. After 20 min, add TMS-ketene (0.25 g, .5 mmol) in CH2Cl2 (10 mL) dropwise and react overnight at 0°C. After the reaction is complete as monitored by TLC plate, add sodium bicarbonate solution to quench, adjust to pH = 9, and extract with CH2Cl2 (3×10 mL). Combine the organic phases, wash with sodium chloride solution, and concentrate to remove the solvent to obtain the intermediate product. At room temperature, the intermediate product is dissolved in CH3CN (10 mL) solution, and KF·2H2O (0.47 g, 5 mmol) is added to react for about 4 h. After the reaction is complete as monitored by TLC plate, filter and dry the filtrate with anhydrous sodium sulfate. Filter and concentrate. Column separation: PE:EA=4:1, 0.5% TEA. Compound 20: pale yellow amorphous solid, 40 mg, yield 22%. 1 H NMR (400MHz, CDCl3) δ8.15(d,J=8.6Hz,2H),7.28(d,J=8.6Hz,2H),6.61(s,1H),6.58(s,1H) ,5.92(dd,J=9.5,0.9Hz,1H),5.77(d,J=1.5Hz,1H),5.60(d,J=1.5Hz,1H),5.13(s,1H),3.8 4(d,J=9.5Hz,1H),3.73(s,3H),3.15–3.00(m,3H),2.98–2.84(m,2H),2.65–2.51(m,4H),2. 43–2.20(m,3H),2.08–1.97(m,1H),1.96–1.88(m,1H),1.82–1.71(m,2H)ppm.HRMS(ESI)m / z calcd for C 30 H 31 N2O9,[M+H]+ 563.2024, found 563.2026. Same as step 1.6, except that raw material 17 is replaced by 18 and 19, and compounds 21 and 22 can be prepared respectively: Compound 21: pale yellow amorphous solid, 708 mg, yield 16%. 1 H NMR (400MHz, CDCl3) δ8.09(dt,J=5.9,2.3Hz,1H),8.01(s,1H),7.47(d,J=5.2Hz,2H),6.63(s,1H),6.57(s,1H),5.94(dd,J=9 .4,0.9Hz,1H),5.79(d,J=1.5Hz,1H),5.65(d,J=1.5Hz,1H),5.15(s,1H),3.86(d,J=9.5Hz,1H),3.76(s,3H),3.16–3.05(m,2H ),3.01(d,J=16.5Hz,1H),2.93(td,J=11.5,6.9Hz,1H),2.80(d,J=16.5Hz,1H),2.72(td,J=12.9,4.5Hz,1H),2.64–2.56(m,3H ),2.46(dd,J=14.2,6.8Hz,1H),2.36–2.25(m,1H),2.15–2.06(m,1H),1.97–1.88(m,2H),1.79–1.73(m,2H)ppm.HRMS(ESI)m / z calcd for C 30 H 31 N2O9,[M+H] + 563.2024, found 563.2024. Compound 22: light yellow amorphous solid, 1.20 g, yield 76%. HRMS (ESI) m / z calcd for C 24 H 27 N2O9,[M+H] + 487.1711, found 487.1712. Step 1.7 Preparation of compound I-2-1 General operation: Under argon protection, add the prepared CH3ONa solution in CH3OH (0.05 g, 1 mmol) to a solution of p-nitrobenzene cephalotaxolide 20 (0.56 g, 1 mmol) in CH3OH (10 mL) slowly at room temperature, and react at room temperature (about 20 min). After the reaction is complete as monitored by TLC plate, add saturated ammonium chloride solution (10 mL) to quench. Concentrate (remove methanol), add 10 mL of water and 10 mL of CH2Cl2, stir and separate, extract the aqueous phase with CH2Cl2 (3×10 mL), combine the organic phases, and concentrate to remove some solvents. Add pH=6.8 buffer solution (2×10 mL) to wash until cephalotaxine is completely removed, wash with sodium bicarbonate solution and sodium chloride solution, and dry with anhydrous sodium sulfate. Filter and concentrate. Column separation PE:EA=4:1, 0.5% TEA. Compound I-2-1: pale yellow amorphous solid, 25 mg, yield 52%. 1 H NMR (400MHz, CDCl3) δ8.13(d,J=8.6Hz,2H),7.25(d,J=8.4Hz,2H),6.58(s,1H),6.56(s,1H),6.04(d,J=9.7Hz,1H),5 .83(d,J=1.6Hz,1H),5.74(d,J=1.6Hz,1H),5.11(s,1H),3.81(d,J=9.8Hz,1H),3.69(s,3H),3.65(s,1H),3.59(s,3H ),3.19–3.05(m,2H),2.94(td,J=11.6,6.9Hz,1H),2.75(td,J=12.7,5.3Hz,1H),2.66–2.54(m,2H),2.49–2.32(m,2H ),2.29(d,J=16.4Hz,1H),2.11–1.96(m,2H),1.92(ddd,J=12.2,7.6,4.6Hz,1H),1.82–1.69(m,4H)ppm.HRMS(ESI)m / z calcd for C 31 H 35 N2O 10 ,[M+H] + 595.2286, found 595.2288. Same as step 1.7, except that the raw material 20 is replaced by 21 and 22 to prepare compounds I-2-2 to I-2-4 respectively: Compound I-2-2: pale yellow amorphous solid, 516 mg, yield 69%. 1H NMR (400MHz, CDCl3) δ8.05(d,J=7.0Hz,1H),7.96(s,1H),7.47–7.41(m,2H),6.57(s,1H),6.56(s,1H),6.06(d,J=9.7Hz,1 H),5.83(s,1H),5.76(s,1H),5.14(s,1H),3.83(d,J=9.8Hz,1H),3.73(s,3H),3.68(s,1H),3.59(s,3H),3.21–3.07(m,2H) ,2.98(td,J=11.8,10.8,6.3Hz,1H),2.78(td,J=13.0,5.1Hz,1H),2.70–2.59(m,2H),2.46(td,J=13.1,4.4Hz,1H),2.38( dd,J=14.0,6.8Hz,1H),2.28(d,J=16.6Hz,1H),2.12–2.04(m,1H),2.00–1.90(m,3H),1.82–1.72(m,3H)ppm.HRMS(ESI)m / z calcd for C 31 H 35 N2O 10 ,[M+H] + 595.2286, found 595.2284. Compound I-2-3: light yellow amorphous solid, 720 mg, yield 75%. HRMS (ESI) m / z calculated for C 25 H 31 N2O 10 ,[M+H] + 519.1973, found 519.1970. Compound I-2-4: light yellow amorphous solid, 680 mg, yield 70%. HRMS (ESI) m / z calculated for C 26 H 33 N2O 10 ,[M+H] + 533.2130, found 533.2135. Example 2 Preparation of Taxol alkaloid analog I-2-5 I-2-2 (1 mmol) was dissolved in 1 mL of AcOH, and Zn powder (20 mmol) was added. The reaction was allowed to proceed at room temperature. After the reaction was completed, the mixture was filtered through diatomaceous earth, and the diatomaceous earth was washed with CH2Cl2 to obtain a filtrate. CH2Cl2 and sodium bicarbonate solution were added to the filtrate, and the mixture was stirred for 30 min. The aqueous phase was extracted with CH2Cl2, and the organic phases were combined, dried, filtered, and concentrated. Column chromatography was performed to obtain a light yellow solid product of the title compound I-2-5 (yield 93%). 1 H NMR (400MHz, CDCl3) δ7.05(t,J=7.7Hz,1H),6.59(s,1H),6.55(s,1H),6.53–6.48(m,2H),6.44(t,J=2.0Hz,1 H),6.05(d,J=9.8Hz,1H),5.84(d,J=1.6Hz,1H),5.75(d,J=1.6Hz,1H),5.08(s,1H),3.80(d,J=9.8Hz,1H),3 .70(s,3H),3.58(s,4H),3.20–3.09(m,2H),3.02–2.93(m,1H),2.64–2.50(m,3H),2.38(dd,J=14.2,6.8Hz,1 H),2.33–2.23(m,2H),2.07–1.92(m,3H),1.82–1.74(m,2H),1.70(dt,J=11.9,5.7Hz,2H)ppm.HRMS(ESI)m / z calcd for C 31 H 37 N2O8,[M+H] + 565.2544, found 565.2541. Example 3 Preparation of Compounds I-2-6 to I-2-8 Refer to Example 2, except that the raw material I-2-2 is replaced by I-2-1, I-2-3 and I-2-4 to prepare compounds I-2-6 to I-2-8 respectively. Compound I-2-6: pale yellow amorphous product, yield 90%. HRMS (ESI) m / z calcd for C 31 H 37 N2O8,[M+H] + 565.2544, found 565.2540. The light yellow amorphous solid product of compound I-2-7 has a yield of 88%. HRMS (ESI) m / z calculated for C 25 H 33N2O8,[M+H] + 489.2231, found 489.2230. The light yellow amorphous solid product of compound I-2-8 has a yield of 92%. HRMS (ESI) m / z calculated for C 26 H 35 N2O8,[M+H] + 503.2388, found 503.2392. Example 4 Preparation of Taxol alkaloid analog I-2-9 Under argon protection, TEA (3 mmol) and acetyl chloride (1.1 mmol) were added dropwise to CH2Cl2 (5 mL) of I-2-5 (1 mmol) at 0°C. After the addition was complete, the mixture was moved to room temperature for overnight reaction. After the reaction was completed by monitoring on a TLC plate, sodium bicarbonate solution was added to quench the reaction, the pH was adjusted to 8, and CH2Cl2 was extracted. The organic phases were combined, dried, filtered, and concentrated. Column chromatography was performed to obtain the light yellow solid product of the title compound (I-2-9) (yield 93%). 1 H NMR (400MHz, CDCl3) δ7.32(d,J=7.9Hz,1H),7.25(s,2H),7.20(t,J=7.8Hz,1H),6.84(d,J=7.5Hz,1H),6.59(s,1H), 6.55(s,1H),6.04(d,J=9.7Hz,1H),5.83(d,J=1.4Hz,1H),5.72(d,J=1.5Hz,1H),5.09(s,1H),3.80(d,J=9.8Hz,1H) ,3.70(s,3H),3.58(s,4H),3.20–3.06(m,2H),3.01–2.89(m,1H),2.66–2.56(m,3H),2.38(dd,J=14.2,6.9Hz,1H),2 .33–2.27(m,2H),2.16(s,3H),2.06–1.97(m,3H),1.96–1.87(m,2H),1.72(dt,J=11.9,5.7Hz,2H)ppm.HRMS(ESI)m / z calcd for C 33 H 39 N2O9,[M+H] + 607.2650, found 607.2651. Example 5 Preparation of Compounds I-2-10 and I-2-12 Refer to Example 4, except that the raw material I-2-5 is replaced by I-2-6 to I-2-8 to prepare compounds I-2-10 to I-2-12, respectively. Compound I-2-10: light yellow solid product, yield 90%. HRMS (ESI) m / z calculated for C 33 H 39 N2O9,[M+H] + 607.2650, found 607.2651. Compound I-2-11: light yellow solid product, yield 88%. HRMS (ESI) m / z calculated for C 27 H 35 N2O9,[M+H] + 531.2337, found 531.2339. Compound I-2-12: light yellow solid product, yield 88%. HRMS (ESI) m / z calculated for C 28 H 37 N2O9,[M+H] + 545.2494, found 545.2490. Example 6 Preparation of Compounds I-2-13 to I-2-22 Refer to the preparation method of compound I-2-9 in Example 5, except that different acid chlorides are used instead of acetyl chloride to react with compound I-2-7 or I-2-8 to prepare compounds I-2-13 to I-2-22, respectively. Example 7 Preparation of Compounds I-2-23 to I-2-28 and I-1-100 Refer to Example 4, except that different acid chlorides are used instead of acetyl chloride to react with compound I-2-5 to prepare compounds I-2-23 to I-2-28 and I-1-100, respectively. Example 8: Preparation of Taxol analog I-1-1 Under argon protection, p-toluene isocyanate (1 mmol) was added dropwise to CH2Cl2 (5 mL) of I-2-5 (1 mmol). After the addition was complete, the reaction was allowed to react overnight at room temperature. After the reaction was complete as monitored by TLC plate, the mixture was concentrated. Column chromatography was performed to obtain the light yellow solid product of the title compound I-1-1 (yield 96%). 1H NMR (400MHz, CDCl3) δ7.23(d,J=8.4Hz,3H),7.19(d,J=7.9Hz,1H),7.13(d,J=8.2Hz,2H),7.04(s,1H),6.83(d,J=6.8Hz,1H), 6.70(d,J=7.5Hz,1H),6.56(s,1H),6.54(s,1H),6.02(d,J=9.7Hz,1H),5.82(d,J=1.4Hz,1H),5.71(d,J=1.4Hz,1H),5.07(s, 1H),3.79(d,J=9.8Hz,1H),3.68(s,3H),3.58(s,3H),3.20–3.03(m,2H),3.00–2.85(m,1H),2.68–2.52(m,3H),2.36(dd,J=14 .2,6.8Hz,2H),2.32(s,3H),2.28(d,J=6.1Hz,1H),2.08–1.97(m,3H),1.97–1.85(m,2H),1.72–1.65(m,2H)ppm.HRMS(ESI)m / z calcd for C 39 H 44 N3O9,[M+H] + 698.3072, found 698.3072. Example 9: Preparation of Taxol analogs I-1-2, I-1-7, I-1-9, I-1-12, I-1-22, I-1-97, I-1-98 and I-1-99 Referring to Example 8, the difference is that cyclopentyl isocyanate, cyclopropyl isocyanate, cyclohexyl isocyanate, tert-butyl isocyanate, benzyl isocyanate, 4-methoxyphenyl isocyanate, 3-chloro-4-tolyl isocyanate, 3,5-ditrifluoromethylphenyl isocyanate, 4-fluorophenyl isocyanate are used instead of p-tolyl isocyanate to prepare compounds I-1-2, I-1-7, I-1-9, I-1-12, I-1-22, I-1-26, I-1-97, I-1-98, I-1-99 respectively. The title compound I-1-2 is a light yellow solid product (yield 69%). 1H NMR (400MHz, CDCl3) δ7.17(d,J=4.9Hz,2H),7.00(s,1H),6.78(d,1H),6.58(s,1H),6.54(s,1H),6.03(d,J=9 .7Hz,1H),5.82(d,J=1.4Hz,1H),5.72(d,J=1.3Hz,1H),5.08(s,1H),3.79(d,J=9.8Hz,1H),3.68(s,3H),3.5 8(s,3H),3.20–3.03(m,3H),3.00–2.87(m,1H),2.65–2.54(m,3H),2.37(dd,J=14.0,6.8Hz,2H),2.29(d,J=1 6.5Hz,2H),2.03(d,J=8.7Hz,2H),2.01–1.90(m,4H),1.77–1.66(m,4H),1.66–1.58(m,4H)ppm.HRMS(ESI)m / z calcd for C 37 H 46 N3O9,[M+H] + 676.3229, found 676.3226. The title compound I-1-7 is a light yellow solid product (yield 92%). 1 H NMR(400MHz,Chloroform-d)δ7.24-7.20(m,1H),7.11(t,J=7.8Hz,1H),7.04(s,2H),6.71(d,J=7.5Hz,1H),6.52(s,1H),6.48(s,1H),5.97 (d,J=9.7Hz,1H),5.76(d,J=1.6Hz,1H),5.65(d,J=1.6Hz,1H),5.20(s,1H),5.02(s,1H),3.73(d,J=9.8Hz,1H),3.63(s,3H),3.58(s,1H), 3.51(s,3H),3.15–2.99(m,2H),2.88(td,J=11.5,6.8Hz,1H),2.64–2.48(m,4H),2.36–2.29(m,1H),2.24(dd,J=17.4,6.2Hz,2H),2.05–1. 93(m,2H),1.93–1.84(m,1H),1.73(d,J=8.0Hz,2H),1.69–1.60(m,2H),0.73(q,J=4.7Hz,2H),0.54(q,J=5.1,4.7Hz,2H)ppm.HRMS(ESI)m / z calcd for C35 H 42 N3O9,[M+H] + 648.2916, found 648.2915. The title compound I-1-9 is a light yellow solid product (yield 89%). 1 H NMR (400MHz, Chloroform-d) δ7.20–7.13(m,2H),7.01(s,1H),6.84(s,1H),6.76(d,J=6.7Hz,1H),6.58(s,1H),6.54(s,1H),6.02(d,J=9.7 Hz,1H),5.82(d,J=1.6Hz,1H),5.72(d,J=1.6Hz,1H),5.08(s,1H),3.79(d,J=9.8Hz,1H),3.67(s,3H),3.64(s,1H),3.59-3.63(s,1H),3.5 8(s,3H),3.19–3.05(m,2H),2.92(td,J=11.5,6.9Hz,1H),2.59(ddt,J=17.6,12.4,6.6Hz,3H),2.41–2.34(m,1H),2.35–2.25(m,2H),2.08 –1.96(m,3H),1.95–1.89(m,3H),1.79–1.64(m,6H),1.57(dd,J=10.5,6.4Hz,1H),1.37–1.28(m,2H),1.17–1.06(m,3H)ppm.HRMS(ESI)m / z calcd for C 38 H 48 N3O9,[M+H] + 690.3385, found 690.3382. The title compound I-1-12 is a light yellow solid product (yield 90%). 1H NMR(400MHz,Chloroform-d)δ7.12-7.04(m,2H),6.95(s,1H),6.76(d,J=12.6Hz,1H),6.66(d,J=6.8Hz,1H),6.51(s,1H),6.47(s, 1H),5.96(d,J=9.7Hz,1H),5.76(d,J=1.5Hz,1H),5.66(d,J=1.6Hz,1H),5.07-4.98(m,2H),3.72(d,J=9.8Hz,1H),3.62-3.57(m,4H ),3.50(s,3H),3.12–2.98(m,2H),2.86(td,J=11.6,7.0Hz,1H),2.60–2.47(m,3H),2.31(dd,J=14.4,6.7Hz,1H),2.23(dd,J=14.7 ,6.9Hz,2H),2.02–1.92(m,2H),1.90–1.82(m,1H),1.70(dd,J=12.1,5.4Hz,2H),1.67–1.61(m,2H),1.28(s,9H)ppm.HRMS(ESI)m / z calcd for C 36 H 46 N3O9,[M+H] + 664.3229, found 664.3226. The title compound I-1-17 is a light yellow solid product (yield 93%). 1 H NMR(400MHz,Chloroform-d)δ7.24–7.17(m,5H),7.09(d,J=6.4Hz,2H),6.95(s,1H),6.82(s,1H), 6.71(d,J=6.7Hz,1H),6.47(s,1H),6.43(s,1H),5.93(d,J=9.6Hz,1H),5.71(d,J=1.6Hz,1H),5.59 (d,J=1.6Hz,1H),5.48(s,1H),5.00(s,1H),4.40–4.28(m,2H),3.69(d,J=9.7Hz,1H),3.60(s,3H), 3.54(s,1H),3.50(s,3H),3.12–2.99(m,2H),2.86(td,J=11.5,6.7Hz,1H),2.63–2.43(m,3H),2.30 (dd,J=14.2,6.6Hz,1H),2.25–2.17(m,2H),2.01–1.91(m,2H),1.89–1.82(m,1H),1.74–1.66(m,J=7.7Hz,2H),1.64–1.57(m,2H)ppm.HRMS(ESI)m / z calcd for C 39 H 44 N3O9,[M+H] + 698.3072, found 698.3070. The title compound I-1-22 is a light yellow solid product (yield 90%). 1 H NMR(400MHz,Chloroform-d)δ7.42-7.38(m,2H),7.23-7.15(m,3H),7.10(t,J=7.7Hz,1H),7.03(s,1H),6.80–6.75(m,2H ),6.72(d,J=7.5Hz,1H),6.50(d,J=12.4Hz,2H),5.99(d,J=9.7Hz,1H),5.80(s,1H),5.69(s,1H),5.04(s,1H),3.76(s,1H ),3.72(s,3H),3.69(s,1H),3.64(s,3H),3.54(s,3H),3.16–3.04(m,2H),2.88(td,J=11.6,6.9Hz,1H),2.66–2.49(m,3H) ,2.33(td,J=6.7Hz,J=12.0,1H),2.30–2.23(m,2H),2.03–1.87(m,3H),1.74(m,2H),1.69–1.61(m,2H)ppm.HRMS(ESI)m / z calcd for C 39 H 44 N3O 10 ,[M+H] + 714.3021, found 714.3023. The title compound I-1-97 is a light yellow solid product (yield 88%). 1H NMR(400MHz,Chloroform-d)δ7.70(d,J=13.8Hz,2H),7.37(d,J=2.2Hz,1H),7.23–7.16(m,1H),7.15–7.08(m,2H),7.07–6.98( m,2H),6.73(d,J=7.5Hz,1H),6.57(s,1H),6.52(s,1H),6.02(d,J=9.7Hz,1H),5.82(d,J=1.5Hz,1H),5.73(d,J=1.6Hz,1H),5. 07(s,1H),3.80(s,1H),3.77(d,J=9.7Hz,1H),3.65(s,3H),3.55(s,3H),3.18–3.03(m,2H),2.95–2.85(m,1H),2.65–2.50(m,3 H),2.39–2.29(m,2H),2.25(s,3H),2.18-2.12(m,1H),2.07–1.87(m,3H),1.80–1.73(m,2H),1.73–1.66(m,2H).HRMS(ESI)m / z calcd for C 39 H 43 ClN3O9,[M+H] + 732.2682, found 732.2678. The title compound I-1-98 is a light yellow solid product (yield 84%). 1H NMR(400MHz,Chloroform-d)δ8.36(s,1H),8.00(s,2H),7.95(s,1H),7.46(s,1H),7.42(d,J=7.3Hz 1H),7.16(t,J=7.8Hz,1H),7.03(s,1H),6.73(d,J=7.6Hz,1H),6.60(s,1H),6.51(s,1H),6.04(d,J=9.7Hz,1H), 5.83(d,J=1.5Hz,1H),5.75(d,J=1.5Hz,1H),5.11(s,1H),4.04(s,1H),3.78(d,J=9.7Hz,1H),3.64(s,3H),3.54( s,3H),3.18–3.05(m,2H),2.93(td,J=11.4,6.9Hz,1H),2.63(ddd,J=16.4,13.4,7.8Hz,3H),2.42(ddt,J=13.9, 10.5,7.1Hz,2H),2.30(d,J=16.9Hz,1H),2.10–1.97(m,2H),1.97–1.88(m,1H),1.82-1.70(m,4H).HRMS(ESI)m / z calcd for C 40 H 40 F6N3O9,[M+H] + 820.2663, found 820.2652. The title compound I-1-99 is a light yellow solid product (yield 84%). 1H NMR (400MHz, Chloroform-d) δ7.85–7.62(m,2H),7.32–7.22(m,2H),7.19(d,J=8.1Hz,1H),7.12(t,J=7.6Hz,1H),7.05(s,1H),6.90(t,J=8.0 Hz,2H),6.74(d,J=7.6Hz,1H),6.55(s,1H),6.50(s,1H),6.01(d,J=9.7Hz,1H),5.82(d,J=1.6Hz,1H),5.72(d,J=1.6Hz,1H),5.06(s,1H),3.7 7(d,J=9.8Hz,1H),3.66(s,3H),3.59(s,1H),3.55(s,3H),3.19–3.05( m,2H),2.90(td,J=11.5,6.8Hz,1H),2.69–2.48(m,3H),2.40–2.28(m,2 H),2.27(d,J=16.7Hz,1H),2.07–1.99(m,1H),1.97(d,J=16.9Hz,1H),1.95–1.85(m,1H),1.83–1.70(m,2H),1.73–1.64(m,2H).HRMS(ESI)m / z calcd for C 38 H 41 FN3O9,[M+H] + 702.2821, found 702.2829. Example 10: Preparation of Taxol analogs I-1-3 to I-1-36 (compounds other than Example 9) Refer to Example 8, except that different substituted isocyanates are used to prepare compounds I-1-3 to I-1-33 respectively. Example 11: Preparation of Taxol analogs I-1-34 to I-1-63 Refer to Example 8, except that differently substituted isocyanates are used to react with compound I-2-7 to prepare compounds I-1-34 to I-1-63, respectively. Example 12: Preparation of Taxol analogs I-1-64 to I-1-72 Refer to Example 8, except that differently substituted isocyanates are used to react with compound I-2-8 to prepare compounds I-1-64 to I-1-72, respectively. Example 13: Preparation of Taxol analog I-1-73 Refer to Example 8, except that benzoyl isocyanate is used instead of p-tolyl isocyanate to react with compound I-2-5 to prepare compound I-1-73. The title compound I-1-73 is a light yellow solid product (yield 92%). 1 H NMR (400MHz, CDCl3) δ10.80(s,1H),8.75(s,1H),7.94(s,1H),7.82(d,J=8.6Hz,1H),7.65(d,J=7.4Hz,1H),7.54(t,J=7.6Hz,2H),7 .51–7.43(m,2H),6.91(s,1H),6.60(s,1H),6.56(s,1H),6.06(d,J=9.9Hz,1H),5.84(d,J=1.4Hz,1H),5.75(d,J=1.4Hz,1H),5.13( s,1H),3.81(d,J=9.8Hz,1H),3.73(s,3H),3.64(s,1H),3.59(s,3H),3.27–3.00(m,2H),3.00–2.88(m,1H),2.85–2.47(m,3H),2.46 –2.34(m,1H),2.31(d,J=16.6Hz,1H),2.08–1.97(m,2H),1.94(d,J=10.2Hz,1H),1.88–1.65(m,3H),1.58(s,2H)ppm.HRMS(ESI)m / z calcd for C 39 H 42 N3O 10 ,[M+H] + 712.2865, found 712.2865. Example 14: Preparation of Taxol analogs I-1-74 to I-1-81 Refer to Example 8, except that different acyl isocyanates are used instead of p-tolyl isocyanate to react with compound I-2-5, I-2-7 or I-2-8 to prepare compounds I-1-74 to I-1-81 respectively. Example 15: Preparation of Taxol analog I-1-82 Refer to Example 8, except that benzenesulfonyl isocyanate is used instead of p-tolyl isocyanate to prepare compound I-1-82. The title compound I-1-82 is a light yellow solid product (yield 83%). 1H NMR(400MHz, CDCl3) δ7.79(d,J=7.1Hz,2H),7.25–7.11(m,3H),7.10–7.00(m,1H),6.70(d,J=5.8Hz,1H),6.55( s,1H),6.47(s,1H),6.00(d,J=9.4Hz,1H),5.80(d,J=1.4Hz,1H),5.68(d,J=1.4Hz,1H),5.08(s,1H),3.82(d,J =9.1Hz,1H),3.60(s,3H),3.54(s,3H),3.41–3.27(m,1H),3.27–3.12(m,2H),3.12–3.00(m,1H),2.61–2.39(m, 2H),2.36(s,3H),2.31–2.13(m,3H),2.09–1.89(m,3H),1.89–1.72(m,2H),1.72–1.54(m,2H)ppm.HRMS(ESI)m / z calcd for C 39 H 44 N3O 11 S,[M+H] + 762.2691, found 762.2691. Example 16: Preparation of Taxol analogs I-1-83 to I-1-96 Refer to Example 8, except that differently substituted nitrile amines, acyl nitrile amines or differently substituted carbodiimides are reacted with compounds I-2-5, I-2-7 or I-2-8 to prepare compounds I-1-83 to I-1-96, respectively. Example 17: Preparation of β-cyclic lactone harringtonate alkaloids 23-40 The method was carried out with reference to step 1.6 of Example 1, except that α-ketoester bases of Cephalotaxus with different side chain substitutions were reacted with trimethylsilyl ketene to prepare compounds 23-40. Compound 23: light yellow solid, yield 23%. (c 0.45,CHCl3). 1H NMR(400MHz, CDCl3) δ6.60(d,J=2.6Hz,2H),5.92(d,J=9.6Hz,1H),5.86(dd,J=7.3,1.5Hz,2H),5 .09(s,1H),3.82(d,J=9.5Hz,1H),3.69(s,3H),3.13–3.03(m,2H),3.00(d,J=16.5Hz,1H),2.95– 2.89(m,1H),2.74(d,J=16.5Hz,1H),2.62–2.57(m,2H),2.35(dd,J=14.2,6.8Hz,1H),2.09–2.00 (m,3H),1.91(ddd,J=12.1,7.6,4.2Hz,2H),1.80–1.71(m,3H),1.56–1.47(m,2H).HRMS(ESI)m / z calcd for C 26 H 29 F3NO7,[M+H] + 524.1891, found 524.1889. Compound 24: pale yellow solid product (yield 30%). (c 0.7,CHCl3). 1 H NMR(400MHz, CDCl3) δ6.60(d,J=4.2Hz,2H),5.90(d,J=9.5Hz,1H),5.87(dd,J=10.3,1.5Hz,2H),5.11 (s,1H),3.82(d,J=9.4Hz,1H),3.68(s,2H),3.11–3.03(m,2H),3.04(d,J=16.4Hz,1H),2.93(td,J=11 .9,11.4,6.8Hz,1H),2.80(d,J=16.4Hz,1H),2.62–2.56(m,2H),2.36(dd,J=14.0,6.5Hz,1H),2.28–2 .20(m,1H),2.04(ddd,J=12.6,10.8,7.0Hz,3H),1.97–1.88(m,3H),1.75–1.72(m,2H).HRMS(ESI)m / z calcd for C 26 H 27 F5NO7,[M+H] + 560.1702, found 560.1700. Compound 25: pale yellow amorphous solid, yield 50%. 1H NMR (400MHz, CDCl3) δ7.09(dd,J=7.9,5.7Hz,2H),6.98(t,J=8.6Hz,2H),6.63(s,1H),6.59(s,1H),5.95(d,J=9.5Hz,1H) ,5.81(s,1H),5.61(s,1H),5.14(s,1H),3.86(d,J=9.5Hz,1H),3.74(s,3H),3.17–3.06(m,2H),3.01(d,J=16.5Hz,1H),2. 94(td,J=11.7,7.1Hz,1H),2.83(d,J=16.5Hz,1H),2.64–2.56(m,2H),2.48(td,J=12.6,4.7Hz,1H),2.37(dd,J=14.3,6.9 Hz,1H),2.32–2.26(m,1H),2.25–2.17(m,1H),2.10–2.03(m,1H),1.97–1.88(m,2H),1.81–1.74(m,2H)ppm.HRMS(ESI)m / z calcd for C 30 H 31 FNO7,[M+H] + 536.2082, found 536.2085. Compound 26: pale yellow amorphous solid, yield 80%. 1 H NMR (400MHz, CDCl3) δ7.54(d,J=8.0Hz,2H),7.24(d,J=8.0Hz,2H),6.62(s,1H),6.58(s,1H),5.94(dd,J=9.5,0.9Hz,1H),5. 78(d,J=1.5Hz,1H),5.57(d,J=1.5Hz,1H),5.13(d,J=0.9Hz,1H),3.85(d,J=9.5Hz,1H),3.73(s,3H),3.10(ddt,J=13.3,8.9, 6.7Hz,2H),3.02(d,J=16.5Hz,1H),2.93(td,J=11.6,6.9Hz,1H),2.86(d,J=16.5Hz,1H),2.67–2.47(m,3H),2.42–2.28(m,2H ),2.22(ddd,J=14.1,12.1,4.7Hz,1H),2.05(dt,J=12.3,9.6Hz,1H),1.98–1.86(m,2H),1.83–1.70(m,2H)ppm.HRMS(ESI)m / z calcd for C 31H 31 F3NO7,[M+H] + 586.2047, found 586.2053. Compound 27: pale yellow amorphous solid, yield 97%. 1 H NMR(400MHz, CDCl3)δ7.07(q,J=8.1Hz,1H),6.84–6.72(m,2H),6.61(s,1H),6.56(s,1H),5.93(d,J=9.5Hz,1H),5.8 0(s,1H),5.64(s,1H),5.11(s,1H),3.83(d,J=9.6Hz,1H),3.71(s,3H),3.16–3.04(m,2H),3.01(d,J=16.5Hz,1H),2 .92(td,J=11.5,7.0Hz,1H),2.81(d,J=16.6Hz,1H),2.63–2.55(m,2H),2.49(dd,J=12.5,4.7Hz,1H),2.40–2.30(m, 2H),2.17(td,J=13.1,12.4,4.9Hz,1H),2.08–2.01(m,1H),1.95–1.85(m,2H),1.79–1.72(m,2H)ppm.HRMS(ESI)m / z calcd for C 30 H 30 F2NO7,[M+H] + 554.1987, found 554.1990. Compound 28: pale yellow amorphous solid, yield 50%. 1H NMR (400MHz, CDCl3) δ6.71–6.56(m,5H),5.93(d,J=9.5Hz,1H),5.81(d,J=1.6Hz,1H),5.69(d,J=1.5 Hz,1H),5.13(s,1H),3.85(d,J=9.5Hz,1H),3.74(s,3H),3.12–3.05(m,2H),2.99(d,J=16.5Hz,1H),2 .92(td,J=11.9,7.2Hz,1H),2.78(d,J=16.5Hz,1H),2.63–2.55(m,2H),2.49(td,J=12.8,12.3,5.0H z,1H),2.38–2.14(m,3H),2.06–2.01(m,1H),1.96–1.88(m,2H),1.80–1.73(m,2H)ppm.HRMS(ESI)m / z calcd for C 30 H 30 F2NO7,[M+H] + 554.1979, found 554.1990. Compound 29: pale yellow amorphous solid, yield 95%. 1 H NMR (400MHz, CDCl3) δ6.98–6.92(m,1H),6.91–6.82(m,2H),6.62(s,1H),6.56(s,1H),5.95(d,J=9 .5Hz,1H),5.81(d,J=1.5Hz,1H),5.68(d,J=1.5Hz,1H),5.12(s,1H),3.88–3.81(m,1H),3.73(s,3H ),3.15–3.05(m,2H),3.04–2.92(m,2H),2.79(d,J=16.5Hz,1H),2.63–2.55(m,3H),2.40–2.30(m, 2H),2.23–2.12(m,1H),2.10–2.00(m,1H),1.98–1.86(m,2H),1.81–1.72(m,2H)ppm.HRMS(ESI)m / z calcd for C 30 H 30 F2NO7,[M+H] + 554.1983, found 554.1990. Compound 30: pale yellow amorphous solid, yield 97%. 1H NMR(400MHz, CDCl3)δ7.05–6.96(m,2H),6.87(t,J=7.1Hz,1H),6.61(s,1H),6.56(s,1H),5.93(d,J=9.5Hz,1H),5 .80(s,1H),5.66(s,1H),5.11(s,1H),3.84(d,J=9.5Hz,1H),3.72(s,3H),3.15–3.06(m,2H),3.01(d,J=16.5Hz,1H ),2.92(td,J=11.8,7.0Hz,1H),2.79(d,J=16.5Hz,1H),2.66–2.52(m,3H),2.46(dt,J=18.0,9.1Hz,1H),2.35(dd, J=14.2,6.8Hz,1H),2.26–2.19(m,1H),2.07–1.99(m,1H),1.95–1.86(m,2H),1.81–1.69(m,2H)ppm.HRMS(ESI)m / z calcd for C 30 H 30 F2NO7,[M+H] + 554.1983, found 554.1990. Compound 31: pale yellow amorphous solid, yield 89%. 1H NMR (400MHz, CDCl3) δ7.61(dd,J=7.9,1.4Hz,1H),7.48(dd,J=8.3,6.9Hz,1H),7.32(t,J=7.7Hz,1H),7.26(d,J=7.6Hz,1H),6.61(s,1H), 6.54(s,1H),5.97(dd,J=9.5,1.0Hz,1H),5.78(d,J=1.5Hz,1H),5.57(d,J=1.5Hz,1H),5.11(d,J=1.0Hz,1H),3.84(d,J=9.6Hz,1H),3.72( s,3H),3.16–3.06(m,2H),3.02(d,J=16.5Hz,1H),2.92(td,J=11.7,7.0Hz,1H),2.80(d,J=16.5Hz,1H),2.70(td,J=13.0,4.6Hz,1H),2.63 –2.54(m,3H),2.34(dd,J=14.3,6.9Hz,1H),2.23–2.15(m,1H),2.07–2.02(m,1H),1.94–1.88(m,2H),1.79–1.73(m,2H)ppm.HRMS(ESI)m / z calcd for C 31 H 31 F3NO7,[M+H] + 586.2045, found 586.2053. Compound 32: pale yellow amorphous solid, yield 80%. 1H NMR (400MHz, CDCl3) δ7.48(d,J=7.7Hz,1H),7.45–7.36(m,2H),7.31(d,J=7.6Hz,1H),6.62(s,1H),6.57(s,1H),5.96(d,J= 9.5Hz,1H),5.79(d,J=1.5Hz,1H),5.61(d,J=1.5Hz,1H),5.13(s,1H),3.85(d,J=9.5Hz,1H),3.73(s,3H),3.18–3.04(m,2H) ,2.98(d,J=16.5Hz,1H),2.93(td,J=11.5,6.9Hz,1H),2.81(d,J=16.5Hz,1H),2.69–2.49(m,3H),2.42–2.30(m,1H),2.23( td,J=12.9,12.2,4.7Hz,1H),2.11–1.99(m,1H),1.96–1.87(m,1H),1.79–1.72(m,2H),1.71–1.62(m,2H)ppm.HRMS(ESI)m / z calcd for C 31 H 31 F3NO7,[M+H] + 586.2044, found 586.2053. Compound 33: pale yellow amorphous solid, yield 56%. 1 H NMR (400MHz, CDCl3) δ7.32(dd,J=9.1,2.7Hz,1H),7.26–7.22(m,1H),7.18(td,J=8.1,2.6Hz,1H),6.61(s,1H),6.55(s,1H), 5.95(d,J=9.5Hz,1H),5.79(d,J=1.5Hz,1H),5.59(d,J=1.6Hz,1H),5.11(s,1H),3.84(d,J=9.5Hz,1H),3.72(s,3H),3.17–3. 03(m,2H),3.01(d,J=16.6Hz,1H),2.92(td,J=11.6,7.0Hz,1H),2.80(d,J=16.5Hz,1H),2.72–2.44(m,4H),2.34(dd,J=14.3 ,6.9Hz,1H),2.18(ddd,J=14.3,12.1,4.8Hz,1H),2.08–1.98(m,1H),1.97–1.79(m,2H),1.82–1.70(m,2H)ppm.HRMS(ESI)m / z calcd for C31 H 30 F4NO7,[M+H] + 604.1952, found 604.1958. Compound 34: pale yellow amorphous solid, yield 63%. 1 H NMR (400MHz, CDCl3) δ7.54(d,J=8.0Hz,2H),7.24(d,J=8.0Hz,2H),6.62(s,1H),6.58(s,1H),5.94(dd,J=9.5,0.9Hz,1H),5. 78(d,J=1.5Hz,1H),5.57(d,J=1.5Hz,1H),5.13(d,J=0.9Hz,1H),3.85(d,J=9.5Hz,1H),3.73(s,3H),3.10(ddt,J=13.3,8.9, 6.7Hz,2H),3.02(d,J=16.5Hz,1H),2.93(td,J=11.6,6.9Hz,1H),2.86(d,J=16.5Hz,1H),2.67–2.47(m,3H),2.42–2.28(m,2H ),2.22(ddd,J=14.1,12.1,4.7Hz,1H),2.05(dt,J=12.3,9.6Hz,1H),1.98–1.86(m,2H),1.83–1.70(m,2H)ppm.HRMS(ESI)m / z calcd for C 31 H 34 NO7,[M+H] + 532.2331, found 532.2335. Compound 35: pale yellow amorphous solid, yield 89%. 1H NMR (400MHz, CDCl3) δ7.98–7.91(m,1H),7.86(dd,J=7.1,2.2Hz,1H),7.74(d,J=8.2Hz,1H),7.56–7.44(m,2H),7.39(dd,J=8.2,7. 0Hz,1H),7.7.29–7.25(m,1H),6.64(s,1H),6.50(s,1H),6.04(dd,J=9.5,0.9Hz,1H),5.72(d,J=1.5Hz,1H),5.42(d,J=1.5Hz,1H), 5.16(s,1H),3.88(d,J=9.6Hz,1H),3.73(s,3H),3.27–3.13(m,1H),3.15–3.05(m,1H),3.01–2.82(m,4H),2.80(d,J=16.5Hz,1H),2 .69–2.56(m,2H),2.46–2.29(m,2H),2.10–2.00(m,1H),2.00–1.90(m,1H),1.83–1.73(m,2H),1.72–1.67(m,1H)ppm.HRMS(ESI)m / z calcd for C 34 H 34 NO7,[M+H] + 568.2326, found 568.2335. Compound 36: pale yellow amorphous solid, yield 85%. 1 H NMR (400MHz, CDCl3) δ7.84–7.73(m,3H),7.56(s,1H),7.48–7.41(m,2H),7.25(d,J=8.5Hz,1H),6.63(s,1H),6.5 8(s,1H),5.98(d,J=9.5Hz,1H),5.74(s,1H),5.51(s,1H),5.13(s,1H),3.86(d,J=9.5Hz,1H),3.75(s,3H),3.21 –3.04(m,2H),3.01(d,J=16.5Hz,1H),2.98–2.89(m,1H),2.86(d,J=16.5Hz,1H),2.68–2.54(m,3H),2.45(dt,J= 13.0,6.4Hz,1H),2.41–2.26(m,2H),2.09–1.97(m,2H),1.98–1.87(m,1H),1.83–1.71(m,2H)ppm.HRMS(ESI)m / z calcd for C 34 H 34NO7,[M+H] + 568.2321, found 568.2335. Compound 37: pale yellow amorphous solid, yield 89%. 1 H NMR (400MHz, CDCl3) δ7.03(d,J=8.2Hz,2H),6.82(d,J=8.1Hz,2H),6.61(s,1H),6.58(s,1H),5.94(d,J=9.5Hz,1H),5.80(d,J=1.6Hz,1H ),5.61(d,J=1.6Hz,1H),5.12(s,1H),3.84(d,J=9.5Hz,1H),3.78(s,3H),3.73(s,3H),3.18–3.03(m,2H),2.96(d,J=16.7Hz,1H),2.97–2 .87(m,1H),2.78(d,J=16.5Hz,1H),2.66–2.54(m,2H),2.45(td,J=12.8,4.8Hz,1H),2.35(dd,J=14.2,6.9Hz,1H),2.26(td,J=13.1,12. 6,4.6Hz,1H),2.16(ddd,J=16.5,11.7,4.7Hz,1H),2.05(dt,J=12.8,9.6Hz,1H),1.95–1.86(m,2H),1.86–1.70(m,2H)ppm.HRMS(ESI)m / z calcd for C 31 H 34 NO8,[M+H] + 548.2276, found 548.2284. Compound 38: pale yellow amorphous solid, yield 69%. 1 H NMR (400MHz,CDCl3) 1H NMR (400MHz, CDCl3) δ7.11 (s, 4H), 6.63 (s, 1H), 6.59 (s, 1H), 5.89 (dd, J = 37.7, 9.1Hz, 1H), 5.74 (d, J = 10.2Hz, 1H), 5.50(d,1H),5.13(d,J=14.4Hz,1H),3.88(d,J=9.4Hz,1H),3.76(s,3H),3.18(ddt,J=13.5,8.9,6,5Hz,2H),3.08(d ,J=16.5Hz,1H),2.97(td,J=11.4,6.7Hz,1H),2.72(d,J=16.5Hz,1H),2.50–2.27(m,3H),2.24–2.16(m,2H),2.00( ddd,J=14.2,12.2,4.8Hz,1H),1.98(dtJ=12.4,9.7Hz,1H),1.98–1.87(m,2H),1.82–1.67(m,2H)ppm.HRMS(ESI)m / z calcd for C 31 H 31 F3NO8,[M+H] + 602.2002, found 602.1993. Compound 39: pale yellow amorphous solid, yield 89%. 1 H NMR (400MHz, CDCl3) δ7.18(d,J=8.2Hz,2H),7.04(d,J=8.3Hz,2H),6.61(s,1H),6.58(s,1H),5.94(dd,J=9.5,0.9Hz,1H) ,5.80(d,J=1.6Hz,1H),5.59(d,J=1.5Hz,1H),5.11(d,J=0.9Hz,1H),3.84(d,J=9.5Hz,1H),3.72(s,3H),3.17–3.05(m,2H ),2.98(d,J=16.5Hz,1H),2.92(dt,J=12.0,5.8Hz,1H),2.83(d,J=16.5Hz,1H),2.63–2.55(m,2H),2.49–2.40(m,4H),2. 35(dd,J=14.2,6.9Hz,1H),2.30–2.13(m,2H),2.09–2.01(m,1H),1.95–1.85(m,2H),1.80–1.70(m,2H)ppm.HRMS(ESI)m / z calcd for C 31 H 34 NO7S,[M+H]+ 564.2056, found 564.2038. Compound 40: pale yellow amorphous solid, yield 87%. 1 H NMR (400MHz, CDCl3) δ7.58(d,J=8.2Hz,2H),7.52(d,J=8.0Hz,2H),7.44(t,J=7.5Hz,2H),7.39–7.30(m,1H),7.20(d,J=8 .0Hz,2H),6.63(s,1H),6.59(s,1H),5.97(d,J=9.5Hz,1H),5.80(s,1H),5.60(s,1H),5.12(s,1H),3.86(d,J=9.5Hz,1H), 3.74(s,3H),3.18–3.06(m,2H),3.02(d,J=16.6Hz,1H),2.94(td,J=11.7,7.9Hz,1H),2.84(d,J=16.5Hz,1H),2.66–2.48 (m,3H),2.40–2.31(m,1H),2.30–2.18(m,1H),2.12–1.97(m,2H),1.99–1.88(m,2H),1.83–1.71(m,2H)ppm.HRMS(ESI)m / z calcd for C 36 H 36 NO7,[M+H] + 594.2478, found 594.2492. Example 18: Preparation of harringtonide alkaloids I-2-29 to I-2-46 Referring to step 1.7 of Example 1, the difference is that compound 23-40 is used for ring-opening methyl esterification reaction to prepare compounds I-2-29 to I-2-46 respectively: Compound I-2-29: pale yellow solid product (yield 67%). (c 1,CHCl3). 1H NMR (400MHz, CDCl3) δ6.62(s,1H),6.53(s,1H),6.01(dd,J=9.8,1.0Hz,1H),5.86(dd,J=5.9,1.5Hz,2H) ,5.05(s,1H),3.77(d,J=9.8Hz,1H),3.72(s,1H),3.66(s,3H),3.57(s,3H),3.14–3.04(m,2H),2.94(td ,J=11.4,6.8Hz,1H),2.62–2.56(m,3H),2.37(dd,J=14.0,6.7Hz,1H),2.24(d,J=16.5Hz,1H),2.05–2.0 2(m,2H),1.95–1.86(m,2H),1.87(d,J=16.5Hz,1H),1.81–1.70(m,3H),1.53–1.49(m,2H).HRMS(ESI)m / z calcd for C 27 H 33 F3NO8,[M+H] + 556.2153, found 556.2145. Compound I-2-30: pale yellow solid product (yield 85%). (c 1.1,CHCl3). 1 H NMR (400MHz, CDCl3) δ6.64(s,1H),6.53(s,1H),6.03(d,J=9.8Hz,1H),5.87(d,J=5.5Hz,2H),5.07(s,1H),3.78(d,J=9.9Hz,1H), 3.70(s,1H),3.63(s,3H),3.58(s,3H),3.13–3.03(m,2H),2.95(td,J=11.4,6.6Hz,1H),2.63–2.56(m,2H),2.39(dd,J=13.9,6.5 Hz,1H),2.29(d,J=16.6Hz,1H),2.08–2.00(m,2H),1.97–1.87(m,3H),1.78–1.67(m,4H).HRMS(ESI)m / z calcd for C 27 H 31 F5NO8,[M+H] + 592.1965, found 592.1962. Compound I-2-31: pale yellow amorphous solid, yield 55%.1 H NMR (400MHz, CDCl3) δ7.05(dd,J=8.5,5.6Hz,2H),6.95(t,J=8.7Hz,2H),6.58(s,1H),6.55(s,1H),6.05(dd,J =9.8,0.9Hz,1H),5.84(d,J=1.6Hz,1H),5.73(d,J=1.6Hz,1H),5.09(s,1H),3.81(d,J=9.8Hz,1H),3.69(s,3H ),3.61(s,1H),3.59(s,3H),3.21–3.06(m,2H),2.97(td,J=11.3,6.7Hz,1H),2.68–2.55(m,3H),2.42–2.25(m ,2H),2.30(d,J=16.4Hz,1H),2.12–1.88(m,3H),1.98(d,J=16.4Hz,1H),1.83–1.65(m,4H)ppm.HRMS(ESI)m / z calcd for C 31 H 35 FNO8,[M+H] + 568.2341, found 568.2347. Compound I-2-32: pale yellow amorphous solid, yield 50%. 1 H NMR (400MHz, CDCl3) δ7.52(d,J=7.9Hz,2H),7.21(d,J=7.9Hz,2H),6.58(s,1H),6.56(s,1H),6.06(d,J=9.8Hz,1H),5.83(d,J =1.5Hz,1H),5.71(d,J=1.5Hz,1H),5.10(s,1H),3.81(d,J=9.8Hz,1H),3.69(s,3H),3.64(s,1H),3.59(s,3H),3.21–3.05(m,2 H),2.95(td,J=11.6,6.9Hz,1H),2.71(td,J=12.8,5.2Hz,1H),2.61(dd,J=10.7,7.7Hz,2H),2.47–2.34(m,2H),2.30(d,J=16 .5Hz,1H),2.10–2.02(m,1H),1.99(d,J=16.4Hz,1H),1.92(ddd,J=12.2,7.7,4.5Hz,1H),1.82–1.68(m,4H)ppm.HRMS(ESI)m / z calcd for C 29 H 29F3NO6,[M+H] + 618.2305, found 618.2315. Compound I-2-33: pale yellow amorphous solid, yield 82%. 1 H NMR (400MHz, CDCl3) δ7.07(q,J=8.1Hz,1H),6.82–6.70(m,2H),6.59(s,1H),6.54(s,1H),6.04(d,J=9.8Hz,1H),5.85(d ,J=1.6Hz,1H),5.75(d,J=1.6Hz,1H),5.08(s,1H),3.80(d,J=9.8Hz,1H),3.67(s,3H),3.64(s,1H),3.58(s,3H),3.23– 3.05(m,2H),2.95(td,J=11.5,7.0Hz,1H),2.66–2.54(m,3H),2.46(dd,J=12.0,5.7Hz,1H),2.36(dd,J=14.2,6.9Hz,1H ),2.28(d,J=16.5Hz,1H),2.09–1.99(m,1H),1.96–1.87(m,2H),1.80–1.72(m,2H),1.73–1.65(m,2H)ppm.HRMS(ESI)m / z calcd for C 31 H 34 F2NO8,[M+H] + 586.2248, found 586.2252. Compound I-2-34: pale yellow amorphous solid, yield 70%. 1 H NMR (400MHz, CDCl3) δ6.66–6.58(m,3H),6.58(s,1H),6.56(s,1H),6.04(d,J=9.5Hz ,1H),5.84(m,1H),5.78(s,1H),5.11(s,1H),3.81(d,J=9.6Hz,1H),3.70(s,3H),3. 63(s,1H),3.59(s,3H),3.20–3.00(m,2H),2.94(td,J=11.6,7.2Hz,1H),2.66–2.49 (m,3H),2.41–2.24(m,3H),2.09–1.86(m,3H),1.82–1.68(m,4H)ppm.HRMS(ESI)m / z calcd for C 31 H 34 F2NO8,[M+H]+ 586.2246, found 586.2252. Compound I-2-35: pale yellow amorphous solid, yield 41%. 1 H NMR (400MHz, CDCl3) δ6.93(td,J=8.7,4.4Hz,1H),6.89–6.77(m,2H),6.59(s,1H),6.54(d,J=5.7Hz,1H),6.04(d,J= 9.8Hz,1H),5.85(d,J=1.6Hz,1H),5.77(d,J=1.6Hz,1H),5.09(s,1H),3.80(d,J=9.8Hz,1H),3.68(s,3H),3.65(s,1 H),3.58(s,3H),3.22–3.07(m,2H),2.94(td,J=11.6,7.0Hz,1H),2.66–2.54(m,3H),2.48–2.32(m,2H),2.28(d,J=1 6.5Hz,1H),2.09–2.00(m,1H),1.96–1.88(m,2H),1.82–1.72(m,2H),1.70(dd,J=9.8,7.4Hz,2H)ppm.HRMS(ESI)m / z calcd for C 31 H 34 F2NO8,[M+H] + 586.2243, found 586.2252. Compound I-2-36: pale yellow amorphous solid, yield 47%. 1H NMR (400MHz, CDCl3) δ7.03–6.93(m,2H),6.87(dd,J=8.3,5.3Hz,1H),6.59(s,1H),6.54(s,1H),6.05(d,J=9.7H z,1H),5.85(d,J=1.5Hz,1H),5.76(d,J=1.6Hz,1H),5.09(s,1H),3.80(d,J=9.8Hz,1H),3.69(s,3H),3.66(s,1H ),3.59(s,3H),3.23–3.06(m,2H),2.95(td,J=11.6,7.0Hz,1H),2.71–2.48(m,4H),2.37(dd,J=14.2,6.9Hz,1H ),2.28(d,J=16.6Hz,1H),2.05(td,J=12.4,9.5Hz,1H),1.96–1.86(m,2H),1.80–1.64(m,4H)ppm.HRMS(ESI)m / z calcd for C 31 H 34 F2NO8,[M+H] + 586.2254, found 586.2252. Compound I-2-37: pale yellow amorphous solid, 118 mg, yield 47%. 1 H NMR (400MHz, CDCl3) δ7.45(d,J=7.9Hz,1H),7.38(t,J=7.7Hz,1H),7.34(s,1H),7.30(d,J=7.5Hz,1H),6.58(s,1H),6.56(s, 1H),6.07(d,J=9.8Hz,1H),5.84(d,J=1.7Hz,1H),5.75(d,J=1.7Hz,1H),5.12(s,1H),3.82(d,J=9.9Hz,1H),3.69(s,3H),3. 66(s,1H),3.59(s,3H),3.21–3.07(m,2H),3.00–2.90(m,1H),2.73(td,J=13.0,5.0Hz,1H),2.62(t,J=9.2Hz,2H),2.47–2.3 3(m,2H),2.28(d,J=16.5Hz,1H),2.06(q,J=10.1Hz,1H),1.98–1.91(m,2H),1.76(dd,J=12.2,7.5Hz,4H)ppm.HRMS(ESI)m / z calcd for C 29 H 29 F3NO6,[M+H]+ 618.2307, found 618.2315. Compound I-2-38: pale yellow amorphous solid, yield 60%. 1 H NMR (400MHz, CDCl3) δ7.59(d,J=7.8Hz,1H),7.45(t,J=7.5Hz,1H),7.27(q,J=8.0Hz,2H),6.56(s,1H),6.53(s,1H),6.03(d,J=9.8Hz,1H),5.84(d ,J=1.6Hz,1H),5.71(d,J=1.6Hz,1H),5.08(s,1H),3.79(d,J=9.8Hz,1H) ,3.69(s,3H),3.68(s,1H),3.60(s,3H),3.17(td,J=12.0,11.3,6.7Hz,1H ),3.15–3.05(m,1H),2.94(td,J=11.6,7.0Hz,1H),2.82(td,J=13.0,4.3 Hz,1H),2.66–2.52(m,3H),2.35(dd,J=14.2,6.9Hz,1H),2.28(d,J=16.5 Hz,1H),2.08–1.98(m,1H),1.92(dt,J=9.0,4.7Hz,1H),1.86(d,J=16.5Hz,1H),1.75(dt,J=13.8,5.1Hz,2H),1.68–1.59(m,2H)ppm.HRMS(ESI)m / z calcd for C 32 H 35 F3NO8,[M+H] + 618.2312, found 618.2315. Compound I-2-39: pale yellow amorphous solid, yield 84%. 1H NMR(400MHz, CDCl3)δ7.30(dd,J=9.4,2.7Hz,1H),7.26–7.18(m,1H),7.20–7.11(m,1H),6.57(s,1H),6.53(s,1H),6.02(d,J=9 .8Hz,1H),5.84(d,J=1.6Hz,1H),5.73(d,J=1.6Hz,1H),5.09(s,1H),3.79(d,J=9.8Hz,1H),3.69(s,3H),3.68(s,1H),3.60(s,3 H),3.22–3.05(m,2H),2.94(td,J=11.6,7.0Hz,1H),2.78(td,J=13.3,4.7Hz,1H),2.64–2.45(m,3H),2.35(dd,J=14.2,6.9Hz, 1H),2.27(d,J=16.5Hz,1H),2.08–1.96(m,1H),1.95–1.89(m,1H),1.86(d,J=16.6Hz,1H),1.81–1.63(m,4H)ppm.HRMS(ESI)m / z calcd for C 32 H 34 F4NO8,[M+H] + 636.2212, found 636.2221. Compound I-2-40: pale yellow amorphous solid, yield 60%. 1 H NMR (400MHz, CDCl3) δ7.11 (s, 4H), 6.58 (s, 1H), 6.56 (s, 1H), 6.05 (d, J = 10.0Hz, 1H), 5.83 (d ,J=1.5Hz,1H),5.71(d,J=1.6Hz,1H),5.10(s,1H),3.81(d,J=9.8Hz,1H),3.69(s,3H),3.59 (s,3H),3.56(s,1H),3.20–3.03(m,2H),2.96(td,J=11.4,6.9Hz,1H),2.68–2.54(m,3H),2. 43–2.26(m,3H),2.09–1.96(m,2H),1.98–1.87(m,1H),1.82–1.67(m,4H)ppm.HRMS(ESI)m / z calcd for C 32 H 35 F3NO9,[M+H] + 634.2263, found 634.2264. Compound I-2-41: pale yellow amorphous solid, yield 56%. 1 H NMR (400MHz, CDCl3) δ7.18(d,J=8.2Hz,2H),7.03(d,J=8.2Hz,2H),6.59(s,1H),6.55(s,1H),6.06(d,J =9.8Hz,1H),5.84(d,J=1.6Hz,1H),5.73(d,J=1.6Hz,1H),5.09(s,1H),3.80(d,J=9.8Hz,1H),3.69(s, 3H),3.61(s,1H),3.58(s,3H),3.20–3.06(m,2H),2.95(td,J=11.6,7.0Hz,1H),2.66–2.56(m,3H),2.4 6(s,3H),2.41–2.26(m,3H),2.10–2.01(m,1H),2.00–1.88(m,2H),1.81–1.64(m,4H)ppm.HRMS(ESI)m / z calcd for C 32 H 38 NO8S,[M+H] + 596.2313, found 596.2318. Compound I-2-42: pale yellow amorphous solid, yield 71%. 1 H NMR (400MHz, CDCl3) δ7.10(d,J=7.6Hz,2H),7.02(d,J=7.7Hz,2H),6.60(s,1H),6.57(s,1H),6. 08(d,J=9.8Hz,1H),5.84(d,J=1.6Hz,1H),5.74(d,J=1.6Hz,1H),5.11(s,1H),3.82(d,J=9.8Hz, 1H),3.71(s,4H),3.59(s,3H),3.26–3.06(m,2H),2.99(dt,J=12.6,6.2Hz,1H),2.76–2.54(m,3H ),2.44–2.27(m,6H),2.15–2.02(m,1H),2.01–1.89(m,2H),1.84–1.68(m,4H)ppm.HRMS(ESI)m / z calcd for C 32 H 38 NO8,[M+H] + 564.2591, found 564.2597. Compound I-2-43: pale yellow amorphous solid, yield 60%.1 H NMR (400MHz, CDCl3) δ8.09–7.85(m,2H),7.75(d,J=8.2Hz,1H),7.51(dd,J=6.3,3.3Hz,2H),7.42(t,J=7.6Hz,1H),7.36–7.26(m,1H),6 .59(s,1H),6.55(s,1H),6.20(d,J=9.9Hz,1H),5.91–5.82(m,1H),5.71(d,J=1.6Hz,1H),5.21(s,1H),3.88(d,J=9.9Hz,1H),3.82(s,1 H),3.71(s,3H),3.64(s,3H),3.33(td,J=13.1,7.7Hz,1H),3.22–3.07(m,2H),3.09–2.90(m,2H),2.80–2.63(m,2H),2.39(dd,J=14.3, 6.9Hz,1H),2.32(d,J=16.6Hz,1H),2.17–2.06(m,1H),2.05–1.92(m,2H),1.90(d,J=16.5Hz,1H),1.87–1.76(m,3H)ppm.HRMS(ESI)m / z calcd for C 35 H 38 NO8,[M+H] + 600.2592, found 600.2597. Compound I-2-44: pale yellow amorphous solid, 153 mg, yield 61%. 1H NMR (400MHz, CDCl3) δ7.83–7.70(m,3H),7.54(s,1H),7.50–7.37(m,2H),7.25(d,J=9.0Hz,1H),6.59(s,1H),6.57(s, 1H),6.09(d,J=9.7Hz,1H),5.81(s,1H),5.69(s,1H),5.11(s,1H),3.83(d,J=9.6Hz,1H),3.71(s,3H),3.67(s,1H),3 .60(s,3H),3.20(td,J=13.1,7.9Hz,1H),3.11(q,J=8.0,7.3Hz,1H),2.96(td,J=11.5,7.0Hz,1H),2.82(td,J=12.8, 5.3Hz,1H),2.68–2.47(m,3H),2.44–2.30(m,2H),2.05(dt,J=25.3,13.3Hz,2H),1.97–1.73(m,5H)ppm.HRMS(ESI)m / z calcd for C 35 H 38 NO8,[M+H] + 600.2600, found 600.2597. Compound I-2-45: pale yellow amorphous solid, yield 56%. 1 H NMR (400MHz, CDCl3) δ7.02(d,J=8.3Hz,2H),6.82(d,J=8.5Hz,2H),6.59(s,1H),6.55(s,1H),6.06(d,J=9.8Hz,1H ),5.83(d,J=1.6Hz,1H),5.73(d,J=1.6Hz,1H),5.09(s,1H),3.81(d,J=9.9Hz,1H),3.78(s,4H),3.70(s,3H),3.58 (s,3H),3.21–3.07(m,2H),2.97(td,J=11.3,6.5Hz,1H),2.65–2.57(m,3H),2.41–2.26(m,3H),2.30(d,J=16.4Hz, 1H),2.06(dt,J=12.0,9.6Hz,1H),1.99–1.89(m,2H),1.96(d,J=16.4Hz,1H),1.81–1.67(m,4H)ppm.HRMS(ESI)m / z calcd for C 32 H 38 NO9,[M+H] +580.2544, found 580.2547. Compound I-2-46: pale yellow amorphous solid, yield 50%. 1 H NMR (400MHz, CDCl3) δ7.57(d,J=7.0Hz,2H),7.51(d,J=7.9Hz,2H),7.43(t,J=7.5Hz,2H),7.33(t,J=6.8Hz,1H),7.18(d,J=7 .8Hz,2H),6.60(s,1H),6.56(s,1H),6.08(d,J=9.8Hz,1H),5.84(d,J=1.6Hz,1H),5.73(d,J=1.7Hz,1H),5.10(s,1H),3.82(d ,J=9.8Hz,1H),3.72(s,3H),3.64(s,1H),3.59(s,3H),3.24–3.06(m,2H),2.96(td,J=11.6,6.9Hz,1H),2.76–2.55(m,3H),2. 47–2.28(m,3H),2.10–2.02(m,1H),1.99(d,J=16.5Hz,1H),1.93(dd,J=9.6,5.5Hz,1H),1.83–1.72(m,4H)ppm.HRMS(ESI)m / z calcd for C 37 H 40 NO8,[M+H] + 626.2746, found 626.2754. Example 19: Preparation of Ketoximes General operation: Under argon protection, add cinchonine catalyst (0.16 mmol) and m-nitrobenzoic acid (0.8 mmol) to a solution of α-ketoester (4 mmol) in acetone (5 mL) at room temperature. After reacting for 8 h, remove most of the solvent and separate by column chromatography to obtain the ketone analogue. At room temperature, the ketone compound (2 mmol) was dissolved in CH3CN / H2O (v / v=9:1, 5 mL), and hydroxylamine hydrochloride (2 mmol) and sodium acetate (2.5 mmol) were added under stirring. After the reaction was complete, saturated NaHCO3 was added to quench the reaction, and the reaction was extracted with CH2Cl2. The organic phases were combined, washed with saturated NaCl, and dried over anhydrous Na2SO4. The solvent was removed by rotary evaporation to obtain E / Z ketoxime analogs. Referring to the above method, the following compounds were obtained: Compound I-2-47: Column chromatography PE:EA=7:1, 0.5% TEA to obtain a yellow amorphous solid (yield 87%). 1 H NMR (400MHz, CDCl3): δ6.60(s,1H),6.55(s,1H),5.98(d,J=9.8Hz,1H),5.85(dd,J=13.6,1.5Hz,2H),5.79–5.64(m ,1H),5.03(s,1H),5.00–4.87(m,2H),3.76(d,J=9.8Hz,1H),3.67(s,3H),3.57(s,1H),3.10(ddd,J=23.8,13.2,7.6 Hz,2H),2.92(td,J=11.6,7.0Hz,1H),2.63–2.52(m,2H),2.46(d,J=17.5Hz,1H),2.36(dd,J=14.1,6.9Hz,1H),2.22 (d,J=17.5Hz,1H),2.11–1.95(m,2H),1.89(s,3H),1.87–1.67(m,4H),1.55–1.38(m,2H)ppm; HRMS-ESI(m / z):Calcd for C 27 H 34 NO7[M+H] + 484.2336.Found 484.2257. Compound I-2-48: Column chromatography PE:EA=7:1, 0.5% TEA to obtain a yellow amorphous solid (yield 96%). 1 H NMR (400MHz, CDCl3): δ6.60(s,1H),6.54(s,1H),5.96(d,J=9.8Hz,1H),5.87–5.80(m,2H),5.02(s,1H),5.03–4. 94(m,1H),3.75(d,J=9.8Hz,1H),3.66(s,3H),3.56(s,1H),3.20–3.02(m,2H),2.92(td,J=11.5,6.9Hz,1H),2.62 –2.51(m,2H),2.42(d,J=17.3Hz,1H),2.36(dd,J=14.2,7.0Hz,1H),2.13(d,J=17.4Hz,1H),2.07–1.93(m,3H),1 .91–1.85(m,1H),1.88(s,3H),1.75(dt,J=13.8,7.5Hz,4H),1.65(s,3H),1.56(s,3H)ppm.HRMS-ESI(m / z):Calcd for C29 H 38 NO7[M+H] + 512.2649.Found 512.2570. Compound I-2-49: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a yellow amorphous solid (yield 88%). 1 H NMR (400MHz, CDCl3): δ7.10 (dd, J=5.1, 1.2Hz, 1H), 6.90 (dd, J=5.2, 3.4Hz, 1H), 6.73 (d, J=2.3Hz, 1H), 6.60 (s, 1H), 6. 56(s,1H),6.04(d,J=9.8Hz,1H),5.80(dd,J=11.2,1.5Hz,2H),5.05(s,1H),3.78(d,J=9.9Hz,1H),3.70(s,1H),3.67(s ,3H),3.22–3.04(m,2H),3.00–2.82(m,2H),2.65–2.53(m,3H),2.49(d,J=17.6Hz,1H),2.38(dd,J=14.2,6.9Hz,1H),2 .20(d,J=17.6Hz,1H),2.10–1.97(m,1H),1.94–1.88(m,1H),1.89(s,3H),1.84–1.69(m,4H)ppm.HRMS-ESI(m / z):Calcd for C 29 H 34 NO7S[M+H] + 540.2057.Found 540.1987. Compound I-2-50: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a yellow amorphous solid (yield 98%). 1H NMR (400MHz, CDCl3): δ6.94(s,1H),6.82(d,J=8.1Hz,1H),6.68(d,J=8.0Hz,1H),6.57(d,J=3.2Hz,2H),6.03(d,J=9.8Hz,1H),5.77(dd,J =26.9,1.5Hz,2H),5.07(s,1H),4.53(t,J=8.6Hz,2H),3.79(d,J=9.8Hz,1H),3.69(s,3H),3.66(s,1H),3.16(t,J=8.6Hz,2H),3.14–3.04( m,2H),2.93(td,J=11.5,7.0Hz,1H),2.65–2.48(m,3H),2.46(d,J=17.5Hz,1H),2.36(dd,J=14.1,6.9Hz,1H),2.33–2.21(m,1H),2.19(d,J =17.5Hz,1H),2.10–1.99(m,1H),1.94–1.88(m,1H),1.90(s,3H),1.75(p,J=9.2,8.1Hz,2H),1.72–1.59(m,2H)ppm.HRMS-ESI(m / z):Calcd for C 33 H 38 NO8[M+H] + 576.2598.Found 576.2519. Compound I-2-51: Column chromatography PE:EA=5:1,0.5%TEA, yellow amorphous solid (yield 95%) was obtained. HRMS-ESI (m / z):Calcd for C 28 H 38 NO8[M+H] + 500.2643.Found 500.2648. Compound I-3-1: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a yellow amorphous solid (yield 37%). 1H NMR (400MHz, CDCl3): δ8.06 (s, 1H), 6.58 (s, 1H), 6.55 (s, 1H), 5.85 (d, J = 3.3Hz, 2H), 5.79–5.66 (m, 1H), 5.04(s,1H),5.00–4.88(m,2H),3.77(d,J=9.9Hz,1H),3.67(s,3H),3.21–3.02(m,2H),2.99–2.86(m,1H) ,2.65–2.53(m,2H),2.38(dd,J=14.1,6.9Hz,1H),2.10(d,J=16.0Hz,1H),2.05–1.98(m,2H),1.95–1.89 (m,1H),1.78–1.71(m,1H),1.63(s,3H),1.59–1.47(m,1H),0.91–0.80(m,6H)ppm.HRMS-ESI(m / z):Calcd for C 27 H 35 N2O7[M+H] + 499.2445.Found 499.2366. Compound I-3-2: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a yellow amorphous solid (yield 42%). 1 H NMR (400MHz, CDCl3): δ6.60(s,1H),6.58(s,1H),5.93(d,J=9.6Hz,1H),5.83(d,J=19.6Hz,2H),5.06 (s,1H),5.05–4.96(m,2H),3.81(s,1H),3.67(s,3H),3.35(s,1H),3.20–3.05(m,2H),2.94(d,J=8.5H z,1H),2.90–2.75(m,1H),2.63–2.48(m,3H),2.39(dd,J=14.3,6.8Hz,1H),2.18–2.00(m,3H),1.89(d ,J=24.0Hz,4H),1.72(s,3H),1.66(d,J=5.6Hz,3H),1.57(d,J=6.1Hz,3H)ppm.HRMS-ESI(m / z):Calcd for C 29 H 39 N2O7[M+H] + 527.2758.Found 527.2679. Compound I-3-3: Column chromatography PE:EA=5:1, 0.5% TEA, to obtain a yellow amorphous solid (yield 30%) 1 H NMR (400MHz, CDCl3): δ7.60(s,1H),6.58(s,1H),6.55(s,1H),5.93(d,J=9.7Hz,1H),5.84(dd,J=8.9,1.6Hz,2H),5.04(s,1H),5.04–4.95 (m,1H),3.77(d,J=9.7Hz,1H),3.67(s,3H),3.63(s,1H),3.22–3.03(m,2H),2.98–2.86(m,1H),2.63–2.52(m,2H),2.37(dd,J=14.2,7.0Hz ,1H),2.07(d,J=15.9Hz,1H),2.04–1.83(m,4H),1.82–1.69(m,3H),1.65(s,6H),1.56(s,3H),1.53–1.36(m,2H)ppm.HRMS-ESI(m / z):Calcd for C 29 H 39 N2O7[M+H] + 527.2758.Found 527.2679. Compound I-3-5: Column chromatography PE:EA=4:1, 0.5% TEA to obtain a yellow amorphous solid (yield 46%). 1 H NMR (400MHz, CDCl3): δ7.09 (dd, J=5.1, 1.2Hz, 1H), 6.89 (dd, J=5.1, 3.4Hz, 1H), 6.73 (d, J=2.4Hz, 1H), 6.58 (s, 1H), 6 .56(s,1H),5.99(d,J=9.7Hz,1H),5.77(dd,J=34.4,1.6Hz,2H),5.06(s,1H),3.87(s,1H),3.78(d,J=9.7Hz,1H),3.67 (s,3H),3.24–3.02(m,2H),2.99–2.83(m,2H),2.65–2.53(m,2H),2.55–2.42(m,1H),2.39(dd,J=14.5,7.0Hz,1H),2. 13(d,J=18.6Hz,1H),2.10–1.95(m,3H),1.95–1.79(m,3H),1.82–1.68(m,4H),1.63(s,3H)ppm.HRMS-ESI(m / z):Calcd for C 29H 35 N2O7S[M+H] + 555.2166.Found 555.2087. Compound I-3-5: Column chromatography PE:EA=4:1, 0.5% TEA to obtain a yellow amorphous solid (yield 45%). 1 H NMR (400MHz, CDCl3): δ6.95(s,1H),6.84(d,J=8.1Hz,1H),6.67(d,J=8.1Hz,1H),6.57(s,1H),6.56(s,1H),5.99(d,J=9.7Hz,1H),5 .73(dd,J=54.7,1.7Hz,2H),5.08(s,1H),4.53(t,J=8.6Hz,2H),3.80(d,J=9.8Hz,1H),3.70(s,3H),3.23–3.14(m,1H),3.16(t,J=8. 6,7.7Hz,2H),3.14–3.03(m,1H),3.00–2.87(m,1H),2.66–2.46(m,3H),2.38(dd,J=14.2,7.0Hz,1H),2.22–2.08(m,1H),2.12(d,J=1 7.4Hz,1H),2.08–1.95(m,2H),1.99(d,J=17.4Hz,1H),1.96–1.84(m,2H),1.82–1.69(m,4H),1.66(s,3H)ppm.HRMS-ESI(m / z):Calcd for C 33 H 39 N2O8S[M+H] + 591.2707.Found 591.2628. Compound I-3-6: Column chromatography PE:EA=4:1, 0.5% TEA to obtain a yellow amorphous solid (yield 35%). 1H NMR (400MHz, CDCl3): δ6.94(s,1H),6.82(d,J=8.1Hz,1H),6.68(d,J=8.1Hz,1H),6.57(s,1H),6.57(s,1H),6.03(d,J=9.8Hz,1H) ,5.77(dd,J=28.7,1.5Hz,2H),5.07(s,1H),4.54(t,J=8.7Hz,2H),3.79(d,J=9.9Hz,1H),3.69(s,3H),3.65(s,1H),3.23–3.04(m ,3H),3.19(t,J=8.6,7.7Hz,2H),3.00–2.86(m,1H),2.65–2.48(m,4H),2.46(d,J=17.5Hz,1H),2.36(dd,J=14.1,6.9Hz,1H),2.2 8(dd,J=25.2,12.5Hz,1H),2.19(d,J=17.4Hz,1H),1.90(s,4H),1.82–1.69(m,2H),1.69–1.60(m,2H)ppm.HRMS-ESI(m / z):Calcd for C 33 H 39 N2O8S[M+H] + 591.2707.Found 591.2628. Example 20: Preparation of Aldoxime Compounds General operation: Under argon protection, at -60°C, add thioenol silyl ether (2 mmol) dropwise to a solution of α-ketoester (1 mmol) in CH2Cl2 (15 mL). After 10 min, add BF3·OEt2 (3 mmol) dropwise. After the reaction is complete as monitored by TLC plate, add saturated NaHCO3 to quench, extract with CH2Cl2, combine the organic phases, wash with saturated NaCl, and dry with anhydrous Na2SO4. Remove the solvent by rotary evaporation to obtain the thioester intermediate. At room temperature, Pd / C (0.1 mmol) and Et3SiH (2.5 mmol) were added to a solution of thioester in CH2Cl2 (5 mL) and the reaction was monitored until completion. Saturated NaHCO3 was added to quench the reaction, the reaction was filtered through diatomaceous earth, and the mixture was extracted with CH2Cl2. The organic phases were combined, washed with saturated NaCl, and dried over anhydrous Na2SO4. The solvent was removed by rotary evaporation to obtain the aldehyde analog. At room temperature, the intermediate aldehyde (2mmol) was dissolved in CH3CN / H2O (v / v=9:1, 5mL), and hydroxylamine hydrochloride (2mmol) and sodium acetate (2.5mmol) were added under stirring, and the reaction was monitored by TLC plate until it was complete. Saturated NaHCO3 was added to quench, and the mixture was extracted with CH2Cl2. The organic phases were combined, washed with saturated NaCl, and dried over anhydrous Na2SO4. The solvent was removed by rotary evaporation to obtain E / Z aldoxime analogs. Referring to the above method, the following compounds were obtained: Compound I-2-52: Obtained as a pale pink amorphous solid (yield 98%). 1 H NMR (400MHz, CDCl3): δ6.61(s,1H),6.52(s,1H),6.00(d,J=9.8Hz,1H),5.86(dd,J=6.5,1.7Hz,2H),5.04(s,1H), 3.78(d,J=9.8Hz,1H),3.67(s,3H),3.39(s,1H),3.15–3.03(m,2H),2.98–2.89(m,1H),2.61–2.55(m,2H),2.52(d ,J=16.0Hz,1H),2.36(dd,J=14.1,6.8Hz,1H),2.22(s,3H),2.00(d,J=16.0Hz,1H),1.94–1.86(m,1H),1.81–1.69 (m,2H),1.51–1.34(m,3H),1.33–1.21(m,2H),0.99–0.92(m,1H),0.82(t,J=6.4Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 28 H 38 NO7S[M+H] + 532.2370.Found 532.2291. Compound I-2-53: Obtained as a pale pink amorphous solid (yield 90%). 1H NMR (400MHz, CDCl3): δ6.58(s,1H),6.50(s,1H),5.98(d,J=9.8Hz,1H),5.82(dd,J=6.5,1.7Hz,2H),5.69(tt,J=13.1,5.1 Hz,1H),5.03(s,1H),4.98–4.85(m,2H),3.76(d,J=9.8Hz,1H),3.65(s,3H),3.41(s,1H),3.12–3.00(m,2H),2.97–2.83(m ,1H),2.61–2.52(m,2H),2.50(d,J=16.0Hz,1H),2.34(dd,J=14.1,6.8Hz,1H),2.19(s,3H),2.11–2.02(m,1H),2.07(d,J= 16.0Hz,1H),1.93–1.75(m,3H),1.72(p,J=5.9,4.8Hz,2H),1.51(tdd,J=25.4,13.5,4.8Hz,2H)ppm.HRMS-ESI(m / z):Calcd for C 24 H 34 NO7[M+H] + 516.2057.Found 516.1978. Compound I-2-54: obtained as a pale pink amorphous solid (yield 82%). 1 H NMR (400MHz, CDCl3): δ6.59(s,1H),6.50(s,1H),5.99(d,J=9.8Hz,1H),5.83(d,J=13.7Hz,2H),5.03(s,1H),5.02–4 .96(m,1H),3.77(d,J=9.8Hz,1H),3.65(s,3H),3.39(s,1H),3.16–3.01(m,2H),2.98–2.85(m,1H),2.62–2.52(m,2H ),2.48(d,J=15.9Hz,1H),2.35(dd,J=14.2,6.8Hz,1H),2.21(s,3H),2.01–1.94(m,1H),1.98(d,J=15.9Hz,1H),1.9 2–1.85(m,1H),1.74(dd,J=13.7,7.9Hz,3H),1.64(s,3H),1.54(s,3H),1.52–1.35(m,3H)ppm.HRMS-ESI(m / z):Calcd for C 29 H 38 NO7S[M+H] +544.2370.Found 544.2291. Compound I-2-55: obtained as a pink amorphous solid (yield 82%). 1 H NMR (400MHz, CDCl3): δ7.10 (dd, J=5.1, 1.3Hz, 1H), 6.90 (dd, J=5.1, 3.4Hz, 1H), 6.73 (d, J=2.4Hz, 1H), 6.61 (s, 1H), 6.54 (s,1H),6.06(d,J=9.8Hz,1H),5.82(dd,J=24.8,1.6Hz,2H),5.08(s,1H),3.81(d,J=9.8Hz,1H),3.68(s,3H),3.53(s,1H) ,3.12(ddd,J=21.9,13.8,7.7Hz,2H),3.01–2.84(m,2H),2.66–2.51(m,4H),2.38(dd,J=14.0,6.7Hz,1H),2.23(s,3H),2. 11(d,J=16.0Hz,1H),2.09–1.98(m,1H),1.98–1.83(m,2H),1.78(ddt,J=17.6,8.9,4.7Hz,3H)ppm.HRMS-ESI(m / z):Calcd for C 29 H 34 NO7S2[M+H] + 572.1777.Found 572.1698. Compound I-2-56: obtained as a pale pink amorphous solid (yield 89%). 1H NMR (400MHz, CDCl3): δ6.94(s,1H),6.82(d,J=8.1Hz,1H),6.68(d,J=8.1Hz,1H),6.58(s,1H),6.55(s,1H),6.06(d,J=9.7Hz,1H),5.8 0(dd,J=33.6,1.7Hz,2H),5.09(s,1H),4.53(t,J=8.7Hz,2H),3.81(d,J=9.8Hz,1H),3.70(s,3H),3.49(s,1H),3.16(t,J=8.9Hz,2H),3 .11(t,J=6.1Hz,2H),3.01–2.86(m,1H),2.66–2.54(m,3H),2.52(d,J=16.1Hz,1H),2.36(dd,J=14.1,6.9Hz,1H),2.32–2.26(m,1H),2. 23(s,3H),2.09(d,J=16.1Hz,1H),2.07–1.98(m,1H),1.92(ddd,J=12.1,7.6,4.5Hz,1H),1.83–1.61(m,4H)ppm.HRMS-ESI(m / z):Calcd for C 33 H 38 NO8S[M+H] + 608.2319.Found 607.2240. Compound I-2-57: Column chromatography PE:EA=7:1, 0.5% TEA to obtain a yellow amorphous solid (yield 49%). 1H NMR (400MHz, CDCl3): δ8.98(d,J=2.9Hz,1H),6.60(s,1H),6.55(s,1H),5.98(d,J=8.8Hz,1H),5.87(dd,J=8.4,5.6Hz,2H),5.06(s,1H ),3.78(d,J=9.8Hz,1H),3.67(s,3H),3.31(s,1H),3.13–3.04(m,2H),2.94(ddd,J=12.4,10.8,6.7Hz,1H),2.58(td,J=9.3,7.3Hz,2H ),2.36(dd,J=13.9,6.7Hz,1H),2.29(dt,J=17.0,2.7Hz,1H),2.06–2.01(m,1H),1.99(s,1H),1.90(ddd,J=12.1,7.8,4.3Hz,1H),1.7 5(ddt,J=9.5,8.1,5.0Hz,3H),1.67–1.62(m,1H),1.52–1.44(m,2H),1.12–1.01(m,1H),0.90–0.82(m,4H)ppm.HRMS-ESI(m / z):Calcd for C 26 H 34 NO7[M+H] + 472.2336.Found 471.2257. Compound I-2-58: Column chromatography PE:EA=7:1, 0.5% TEA gave a light yellow amorphous solid (yield 51%). 1 H NMR (400MHz, CDCl3): δ8.98(d,J=2.9Hz,1H),6.59(s,1H),6.55(s,1H),5.98(d,J=9.7Hz,1H),5.86(s,2H) ,5.06(s,1H),5.00(t,J=7.2Hz,1H),3.79(d,J=9.7Hz,1H),3.67(s,3H),3.37(s,1H),3.15–3.01(m,2H),2. 97–2.89(m,1H),2.64–2.52(m,2H),2.36(dd,J=14.0,6.7Hz,1H),2.27(dd,J=17.1,3.1Hz,1H),2.10–1.95( m,3H),1.95–1.84(m,2H),1.84–1.70(m,4H),1.65(t,J=2.3Hz,3H),1.56(s,3H)ppm.HRMS-ESI(m / z):Calcd for C 28 H36 NO7[M+H] + 498.2493.Found 498.2414. Compound I-2-59: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a yellow amorphous solid (yield 54%). 1 H NMR (400MHz, CDCl3): δ9.00(d,J=2.5Hz,1H),7.09(d,J=5.2Hz,1H),6.92–6.83(m,1H),6.73(d,J =3.4Hz,1H),6.58(s,1H),6.55(s,1H),6.02(d,J=9.7Hz,1H),5.82(d,J=9.8Hz,2H),3.79(d,J=9. 8Hz,1H),3.67(s,3H),3.43(s,1H),3.14–3.00(m,2H),2.97–2.83(m,2H),2.61-2.52(m,4H),2.41 –2.28(m,2H),2.10–1.95(m,2H),1.94–1.82(m,3H),1.78–1.70(m,2H)ppm.HRMS-ESI(m / z):Calcd for C 28 H 32 NO7S[M+H] + 526.1900 Found 526.1821. Compound I-2-60: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a yellow amorphous solid (yield 62%). 1 H NMR (400MHz, CDCl3): δ9.01(s,1H),6.96(s,1H),6.85(d,J=8.2Hz,1H),6.68(d,J=8.1Hz,1H),6.58 (s,2H),6.05(d,J=9.7Hz,1H),5.82(d,J=18.7Hz,2H),5.11(s,1H),4.54(t,J=8.6Hz,2H),3.82(d,J =9.8Hz,1H),3.72(s,3H),3.43(s,1H),3.24–3.02(m,4H),3.01–2.87(m,1H),2.65–2.55(m,3H),2. 41–2.25(m,2H),2.08–1.98(m,3H),1.98–1.85(m,1H),1.82–1.70(m,4H)ppm.HRMS-ESI(m / z):Calcd for C 32 H36 NO8[M+H] + 562.2442 Found 562.2363. Compound I-2-61: Column chromatography PE:EA=5:1,0.5%TEA, yellow amorphous solid (yield 68%) was obtained. HRMS-ESI (m / z):Calcd for C 27 H 36 NO7[M+H] + 486.2486 Found 486.2480. Compound I-2-62: Column chromatography PE:EA=5:1,0.5%TEA, yellow amorphous solid (yield 65%) was obtained. HRMS-ESI (m / z):Calcd for C 26 H 32 NO7[M+H] + 470.2173 Found 470.2170. Compound I-3-7: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a white amorphous solid (yield 42%). 1 H NMR(400MHz, CDCl3):6.63–6.51(m,3H),5.96(d,J=10.6Hz,1H),5.06(s,1H),3.79(d,J=9.7Hz, 1H),3.71(s,1H),3.68(s,3H),3.18–3.04(m,3H),2.94(td,J=11.6,7.0Hz,1H),2.59(q,J=9.4, 8.8Hz,2H),2.38(dd,J=14.3,6.9Hz,1H),2.14–1.98(m,3H),1.95–1.84(m,1H),1.82–1.70(m,3 H),1.63–1.34(m,4H),1.01–0.88(m,1H),0.84(dd,J=6.6,2.2Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 27 H 37 N2O7[M+H] + 501.2602.Found 501.2523. Compound I-3-8: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a white amorphous solid (yield 32%). 1H NMR (400MHz, CDCl3): δ8.11(s,1H),6.63(s,1H),6.59(s,1H),6.29(dd,J=6.5,3.6Hz,1H),5.96(d,J=9.7Hz,1H),5.88(q,J=1.7Hz,2H ),5.09(s,1H),3.82(d,J=9.7Hz,1H),3.70(s,3H),3.20–3.06(m,3H),2.97(td,J=11.5,6.8Hz,1H),2.66–2.57(m,2H),2.55(dd,J=16 .7,6.6Hz,1H),2.41(dd,J=14.1,6.7Hz,1H),2.06–2.02(m,1H),1.92(ddd,J=12.2,8.0,4.1Hz,1H),1.78(tq,J=8.5,4.2,3.7Hz,2H), 1.68(dd,J=16.8,3.6Hz,1H),1.64–1.44(m,4H),0.96(td,J=12.4,6.2Hz,1H),0.86(dd,J=6.6,2.5Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 27 H 37 N2O7[M+H] + 501.2602.Found 501.2523. Compound I-3-9: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a white amorphous solid (yield 22%). 1H NMR (400MHz, CDCl3): δ6.57(dd,J=6.8,3.2Hz,3H),5.95(d,J=9.7Hz,1H),5.86(dd,J=12.8,1.7Hz,2H),5.06(s,1H), 5.02(t,J=7.0Hz,1H),3.79(d,J=9.7Hz,1H),3.67(s,3H),3.32(s,1H),3.10(ddd,J=21.7,13.9,7.9Hz,2H),2.93(td ,J=11.6,6.9Hz,1H),2.63–2.53(m,2H),2.37(dd,J=14.1,6.8Hz,1H),2.11–1.92(m,2H),1.89(ddd,J=12.1,7.9,4.2 Hz,1H),1.82–1.67(m,2H),1.65(s,3H),1.57(s,3H),1.54–1.39(m,1H),0.92–0.80(m,4H)ppm.HRMS-ESI(m / z):Calcd for C 28 H 37 N2O7[M+H] + 513.2602.Found 513.2523. Compound I-3-10: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a white amorphous solid (yield 23%). 1 H NMR (400MHz, CDCl3): δ6.60(s,2H),6.56(s,1H),6.27(dd,J=6.5,3.7Hz,1H),5.93(d,J=9.5Hz,1H),5.87–5. 80(m,2H),5.07(s,1H),5.02(t,J=7.9Hz,1H),3.79(d,J=9.6Hz,1H),3.68(s,3H),3.16–3.03(m,2H),2.94(td ,J=11.5,6.8Hz,1H),2.63–2.54(m,2H),2.50(dd,J=16.7,6.6Hz,1H),2.43–2.32(m,1H),2.10–1.98(m,1H), 1.93–1.86(m,1H),1.83–1.68(m,2H),1.65(s,3H),1.57(s,3H),0.92–0.80(m,4H)ppm.HRMS-ESI(m / z):Calcd for C 28 H 37 N2O7[M+H] +513.2602.Found 513.2523. Compound I-3-11: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a white amorphous solid (yield 28%). 1 H NMR (400MHz, CDCl3): δ6.59(s,1H),6.58(s,1H),6.53(dd,J=7.9,4.2Hz,1H),5.95(d,J=9.5Hz,1H),5.87(d d,2H),5.05(s,1H),3.79(d,J=9.7Hz,1H),3.67(s,3H),3.29(s,1H),3.18–3.03(m,2H),2.94(td,J=11.5,6 .9Hz,1H),2.64–2.53(m,2H),2.37(dd,J=14.1,6.8Hz,1H),2.14–1.98(m,3H),1.90(ddd,J=12.1,8.1,4.1H z,1H),1.76(ddt,J=14.3,8.8,4.4Hz,4H),1.61–1.40(m,3H),0.92–0.80(m,4H)ppm.HRMS-ESI(m / z):Calcd for C 26 H 35 N2O7[M+H] + 487.2445.Found 487.2366. Compound I-3-12: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a white amorphous solid (yield 35%). 1H NMR (400MHz, CDCl3): δ6.61(s,1H),6.56(s,1H),6.26(dd,J=6.5,3.6Hz,1H),5.93(d,J=9.8Hz,1H) ,5.86(d,J=1.8Hz,2H),5.06(s,1H),3.79(d,J=9.7Hz,1H),3.68(s,3H),3.13–3.05(m,2H),2.99–2. 90(m,1H),2.64–2.48(m,3H),2.39(dd,J=14.1,6.8Hz,1H),2.11–1.98(m,1H),1.95–1.84(m,1H),1. 83–1.60(m,4H),1.61–1.44(m,2H),1.09–0.99(m,1H),0.91–0.80(m,5H)ppm.HRMS-ESI(m / z):Calcd for C 26 H 35 N2O7[M+H] + 487.2445.Found 487.2366. Example 21: Preparation of oxime ester compounds General procedure: Under Ar atmosphere, at 0°C, add Et3N (3 mmol) to a solution of oxime (1 mmol) in CH2Cl2 (5 mL), then add acetic anhydride (1.2 mmol). After the addition is complete, move to room temperature and monitor on a TLC plate until the reaction is complete. Add saturated NaHCO3 to quench, extract with CH2Cl2, combine the organic phases, wash with saturated NaCl, and dry with anhydrous Na2SO4. Remove the solvent by rotary evaporation to obtain a crude product of oxime acetate. Referring to the above method, the following compound was obtained: Compound I-3-13: Column chromatography PE:EA=5:1, 0.5% TEA, to obtain a white amorphous solid (yield 87%). HRMS-ESI (m / z): Calcd for C 29 H 38 N2O8[M+H] + 543.2707.Found 543.2628. 1H NMR (400MHz, CDCl3): δ6.82(dd,J=8.8,3.8Hz,1H),6.53(d,J=3.7Hz,2H),5.85(d,J=8.8Hz,1H),5.81(dd,J=18.3,1.6Hz,2H),5 .01(s,1H),3.74(d,J=9.7Hz,1H),3.64(s,1H),3.61(s,3H),3.05–2.97(m,4H),2.87(td,J=11.5,6.8Hz,1H),2.57–2.49(m,2H), 2.29(ddd,J=18.0,14.2,7.8Hz,3H),2.06(s,3H),1.82(ddd,J=14.9,10.6,4.4Hz,2H),1.70(dt,J=13.1,7.4Hz,2H),1.55(td,J =13.0,4.3Hz,1H),1.40(td,J=13.5,13.1,5.1Hz,1H),0.88–0.82(m,1H),0.77(dd,J=6.6,2.4Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 29 H 39 N2O8[M+H] + 543.2707.Found 543.2628. Compound I-3-14: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a white amorphous solid (yield 55%). 1 H NMR (400MHz, CDCl3): δ6.89(dd,J=8.8,3.8Hz,1H),6.60(s,1H),6.59(s,1H),5.92(d,J=9.7Hz,1H),5.87(dd,J =17.3,1.6Hz,2H),5.07(s,1H),3.80(d,J=9.7Hz,1H),3.68(s,3H),3.13–3.06(m,2H),3.04(s,1H),2.98–2.89( m,1H),2.60(t,J=8.4Hz,2H),2.43–2.29(m,2H),2.13(s,3H),2.10–1.97(m,2H),1.95–1.85(m,2H),1.80–1.70 (m,3H),1.66–1.55(m,3H),1.47(td,J=13.5,12.7,3.9Hz,1H),0.86(t,J=7.1Hz,3H)ppm.HRMS-ESI(m / z):Calcd for C 28 H37 N2O8[M+H] + 529.2551.Found 528.2472. Compound I-3-15: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a white amorphous solid (yield 49%). 1 H NMR (400MHz, CDCl3): δ6.92(dd,J=8.8,3.9Hz,1H),6.60(s,1H),6.58(s,1H),5.91(d,J=9.7Hz,1H),5.86(dd, J=9.7,1.6Hz,2H),5.08(s,1H),5.06–4.97(m,1H),3.81(d,J=9.7Hz,1H),3.68(s,3H),3.14–3.03(m,2H),3.0 9(s,1H),2.92(td,J=11.5,6.8Hz,1H),2.62–2.54(m,2H),2.42–2.26(m,2H),2.13(s,3H),2.10–1.97(m,2H), 1.97–1.79(m,3H),1.81–1.71(m,3H),1.65(s,3H),1.56(s,3H),1.55–1.43(m,1H)ppm.HRMS-ESI(m / z):Calcd for C 30 H 39 N2O8[M+H] + 555.2707.Found 555.2628. Example 22: Preparation of oxime ester compounds General procedure: Under Ar atmosphere, Et3N (3 mmol) was added dropwise to a solution of oxime (1 mmol) in CH2Cl2 (5 mL), followed by acyl chloride (1.2 mmol), and the reaction was monitored by TLC plate until complete. Saturated NaHCO3 was added to quench, and CH2Cl2 was extracted. The organic phases were combined, washed with saturated NaCl, and dried over anhydrous Na2SO4. The solvent was removed by rotary evaporation to obtain a crude oxime ester. Referring to the above method, the following compound was obtained: Compound I-3-16: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a light yellow amorphous solid (yield 44%). 1H NMR (400MHz, CDCl3): δ6.58(d,J=17.9Hz,2H),6.50(d,J=17.5Hz,1H),6.22(ddd,J=17.4,10.5,1.9Hz,1H),5.97–5.80(m,4H),5.03 (s,1H),3.80(d,J=8.8Hz,1H),3.66(s,3H),3.36(s,1H),3.11(dd,J=23.9,8.5Hz,2H),2.92(q,J=10.5Hz,1H),2.62–2.54(m,2H),2 .39(d,J=14.8Hz,1H),2.33(d,J=16.9Hz,1H),2.09–1.96(m,1H),1.93–1.81(m,2H),1.79(d,J=1.8Hz,3H),1.76–1.66(m,3H),1.55 –1.48(m,1H),1.43(dt,J=11.8,5.1Hz,1H),1.30–1.21(m,1H),0.97–0.87(m,1H),0.83(d,J=6.7Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 31 H 41 N2O8[M+H] + 569.2864.Found 569.2785. Compound I-3-17: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a light yellow amorphous solid (yield 57%). 1H NMR (400MHz, CDCl3): δ6.61(s,1H),6.56(s,1H),5.93(d,J=9.7Hz,1H),5.85(dd,J=13.7,1.5Hz,2H),5.03(s,1H),3.79(d,J=9.7 Hz,1H),3.66(s,3H),3.35(s,1H),3.21–3.04(m,2H),2.93(q,J=11.2Hz,1H),2.67(p,J=7.0Hz,1H),2.62–2.54(m,2H),2.38(dd,J =14.2,6.9Hz,1H),2.30(d,J=15.0Hz,1H),2.10–1.96(m,1H),1.93–1.86(m,1H),1.82(d,J=15.0Hz,1H),1.75(s,3H),1.57–1.36 (m,4H),1.23(dd,J=7.0,1.2Hz,6H),1.18–1.06(m,1H),0.95–0.87(m,2H),0.83(dd,J=6.6,2.7Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 32 H 45 N2O8[M+H] + 585.3177.Found 584.3098. Compound I-3-18: Column chromatography PE:EA=2:1, 0.5% TEA to obtain a light yellow amorphous solid (yield 87%). 1H NMR (400MHz, CDCl3): δ7.09(d,J=5.1Hz,1H),6.90(dd,J=5.1,3.5Hz,1H),6.73(t,J=4.2Hz,1H),6.60(s,1H),6.56(s,1 H),6.01(d,J=9.3Hz,1H),5.79(d,J=17.8Hz,2H),5.06(s,1H),3.81(d,J=9.8Hz,1H),3.67(s,3H),3.53(s,1H),3.18(dt ,J=13.0,6.5Hz,1H),3.15–3.04(m,1H),3.00–2.79(m,2H),2.73–2.48(m,4H),2.40(dd,J=14.2,6.9Hz,1H),2.33(d,J=1 5.2Hz,1H),2.02(dd,J=20.7,11.0Hz,2H),1.96–1.81(m,3H),1.63(s,1H),1.27–1.21(m,6H)ppm.HRMS-ESI(m / z):Calcd for C 33 H 41 N2O8S[M+H] + 625.2581.Found 625.2505. Compound I-3-19: Column chromatography PE:EA=2:1, 0.5% TEA to obtain a white amorphous solid (yield 89%). 1H NMR (400MHz, CDCl3): δ6.95 (s, 1H), 6.84 (d, J = 8.1Hz, 1H), 6.67 (d, J = 8.1Hz, 1H), 6. 59(s,1H),6.58(s,1H),6.51(dd,J=17.4,1.4Hz,1H),6.22(dd,J=17.4,10.5Hz,1H) ,5.99(d,J=9.7Hz,1H),5.91(dd,J=10.5,1.5Hz,1H),5.75(dd,J=40.8,1.6Hz,2H), 5.08(s,1H),4.53(t,J=8.6Hz,2H),3.82(d,J=9.7Hz,1H),3.68(s,3H),3.46(s,1H) ,3.32–3.14(m,1H),3.16(t,J=8.8Hz,2H),3.09(td,J=8.5,5.1Hz,1H),2.93(td,J= 11.7,7.0Hz,1H),2.64–2.56(m,2H),2.49(td,J=12.9,4.9Hz,1H),2.40(dd,J=14.4 ,6.7Hz,1H),2.36(d,J=17.4Hz,1H),2.19(td,J=13.0,4.7Hz,1H),2.08–1.85(m,2H ),1.96(d,J=17.4Hz,1H),1.83(s,3H),1.80–1.65(m,4H)ppm.HRMS-ESI(m / z):Calcd for C 36 H 41 N2O9[M+H] + 645.2810.Found 645.2734. Compound I-3-20: Column chromatography PE:EA=2:1, 0.5% TEA to obtain a light yellow amorphous solid (yield 38%). 1H NMR (400MHz, CDCl3): δ6.96 (s, 1H), 6.84 (d, J = 8.1Hz, 1H), 6.67 (d, J = 8.1Hz, 1H),6.58(d,J=6.3Hz,2H),5.99(d,J=9.7Hz,1H),5.76(dd,J=33.8,1.6Hz,2 H),5.08(s,1H),4.53(t,J=8.6Hz,2H),3.83(d,J=9.7Hz,1H),3.69(s,3H),3 .44(s,1H),3.16(t,J=8.8Hz,2H),3.13–3.04(m,2H),2.94(td,J=11.5,6.9Hz ,1H),2.72–2.54(m,3H),2.56–2.44(m,1H),2.40(dd,J=13.7,7.2Hz,1H),2. 33(d,J=15.0Hz,1H),2.22(td,J=12.9,4.5Hz,1H),2.08–1.98(m,1H),1.90( dd,J=13.2,5.1Hz,2H),1.79(s,3H),1.74(dd,J=12.7,5.4Hz,3H),1.68–1.4 8(m,1H),1.23(d,J=7.0Hz,6H),1.20–1.08(m,2H)ppm.HRMS-ESI(m / z):Calcd for C 37 H 45 N2O9[M+H] + 661.3120.Found 661.3122. Compound I-3-21: Column chromatography PE:EA=2:1, 0.5% TEA gave a light yellow amorphous solid (yield 30%). 1H NMR (400MHz, CDCl3): δ6.92(s,1H),6.82(d,J=8.1Hz,1H),6.66(d,J=8.1Hz,1H),6.59(d,J=8.7Hz,2H),5.99(d,J=9.6Hz,1H),5.74( dd,J=54.6,1.6Hz,2H),5.12(s,1H),4.53(t,J=8.7Hz,2H),3.85(d,J=9.6Hz,1H),3.71(s,3H),3.15(t,J=8.8Hz,2H),3.21–3.06(m, 2H),3.05(s,1H),2.95(dt,J=11.5,5.5Hz,1H),2.74(d,J=13.7Hz,1H),2.67–2.52(m,3H),2.45–2.41(m,1H),2.38(dd,J=13.7,7.2H z,1H),2.15–1.98(m,2H),1.99–1.91(m,1H),1.90(s,3H),1.86–1.61(m,5H),1.16(dd,J=15.8,7.0Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 37 H 45 N2O9[M+H] + 661.3120.Found,661.3122. Compound I-3-22: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a yellow amorphous solid (yield 89%). 1 H NMR (400MHz, CDCl3): δ6.63-6.45(m,3H),6.14(dd,J=17.3,10.5Hz,1H),5.96–5.83(m,3H),5.8 0(d,J=11.5Hz,2H),5.06(s,1H),3.78(d,J=9.6Hz,1H),3.65(s,3H),3.17–3.01(m,3H),3.00–2 .87(m,1H),2.66–2.54(m,2H),2.42–2.29(m,2H),2.11–1.96(m,1H),1.95–1.82(m,1H),1.80–1 .67(m,2H),1.66–1.51(m,2H),1.51–1.30(m,4H),0.87–0.77(m,6H)ppm.HRMS-ESI(m / z):Calcd for C 30 H 39 N2O8[M+H] +555.2707.Found 555.2628. Compound I-3-23: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a white amorphous solid (yield 43%). 1 H NMR (400MHz, CDCl3): δ7.03(dd,J=8.9,3.8Hz,1H), 6.58(d,J=7.0Hz,2H), 5.91(d,J=9.7Hz,1H), 5.84(dd,J=9.8,1.5Hz,2H), 5.06(s,1H),3.79(d,J=9.7Hz,1H),3.66(s,3H),3.12–3.03(m,3H),2.92(td,J=11.5,6.8Hz,1H),2.63–2.53(m,4H),2.40–2. 28(m,2H),1.89(ddd,J=12.2,7.8,4.4Hz,1H),1.76(ddd,J=17.9,11.8,5.5Hz,4H),1.59(td,J=13.1,4.3Hz,1H),1.49–1.39( m,2H),1.20(dd,J=7.0,1.5Hz,6H),0.89(ddd,J=12.3,7.5,4.5Hz,1H),0.82(dd,J=6.6,3.1Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 31 H 43 N2O8[M+H] + 571.3020.Found 571.2941. Compound I-3-24: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a white amorphous solid (yield 43%). 1H NMR (400MHz, CDCl3): δ7.03(dd,J=8.9,3.8Hz,1H), 6.58(d,J=7.0Hz,2H), 5.91(d,J=9.7Hz,1H), 5.84(dd,J=9.8,1.5Hz,2H), 5.06(s,1H),3.79(d,J=9.7Hz,1H),3.66(s,3H),3.12–3.03(m,3H),2.92(td,J=11.5,6.8Hz,1H),2.63–2.53(m,4H),2.40–2. 28(m,2H),1.89(ddd,J=12.2,7.8,4.4Hz,1H),1.76(ddd,J=17.9,11.8,5.5Hz,4H),1.59(td,J=13.1,4.3Hz,1H),1.49–1.39( m,2H),1.20(dd,J=7.0,1.5Hz,6H),0.89(ddd,J=12.3,7.5,4.5Hz,1H),0.82(dd,J=6.6,3.1Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 30 H 41 N2O8[M+H] + 557.2860.Found 557.2785. Compound I-3-25: Column chromatography PE:EA=5:1, 0.5% TEA to obtain a white amorphous solid (yield 87%). 1H NMR (400MHz, CDCl3): δ7.09(dd,J=8.8,3.9Hz,1H),6.59(s,1H),6.59(s,1H),5.90(d,J=5.1Hz,1H),5.85(dd,J=1.6Hz,2H),5.08( s,1H),5.02(t,J=6.8Hz,1H),3.81(d,J=9.7Hz,1H),3.68(s,3H),3.08(q,J=6.0Hz,3H),2.93(td,J=11.5,7.0Hz,1H),2.61(dt,J=1 3.9,7.0Hz,3H),2.38(dd,J=14.0,6.7Hz,1H),2.31(dd,J=14.8,8.8Hz,1H),2.10–1.97(m,1H),1.95–1.87(m,1H),1.82–1.71(m,4 H),1.65(s,3H),1.56(s,3H),1.55–1.42(m,1H),1.22(dd,J=7.0,1.3Hz,6H),0.85(d,J=6.6,3.5Hz,2H)ppm.HRMS-ESI(m / z):Calcd for C 32 H 43 N2O8[M+H] + 583.3020.Found 583.2941. Example 23: Preparation of oxime ester compounds General procedure: Naproxen (1 mmol), EDCI (1.1 mmol), DMAP (0.2 mmol) in CH2Cl2 (2 mL) were added dropwise to a solution of oxime (1 mmol) in CH2Cl2 (2 mL) under Ar atmosphere, and the reaction was monitored by TLC plate until completion. Saturated NaHCO3 was added to quench, and CH2Cl2 was extracted. The organic phases were combined, washed with saturated NaCl, and dried over anhydrous Na2SO4. The solvent was removed by rotary evaporation to obtain a crude oxime ester product. Referring to the above method, the following compound was obtained: Compound (I-3-26): Column chromatography PE:EA=4:1, 0.5% TEA gave a light yellow amorphous solid (yield 44%). 1H NMR (400MHz, CDCl3): δ7.70(d,J=9.0Hz,3H),7.42(dd,J=8.4,1.9Hz,1H),7.16–7.09(m,2H),6.56(s,1H),6.47(s,1H),5.90(d,J=9 .6Hz,1H),5.69(dd,J=23.7,1.5Hz,2H),5.01(s,1H),3.91(s,3H),3.72(d,J=8.9Hz,1H),3.64(s,3H),3.28(s,1H),3.15–3.03(m,2 H),2.95–2.85(m,1H),2.61–2.53(m,2H),2.34(dd,J=14.1,6.8Hz,1H),2.25(d,J=15.0Hz,1H),2.04(s,3H),2.02–1.93(m,2H),1.9 2–1.81(m,2H),1.79–1.71(m,3H),1.63(d,J=7.2Hz,3H),1.54–1.36(m,4H),0.82(dd,J=6.6,2.7Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 42 H 51 N2O9[M+H] + 727.3594.Found 727.3516. Compound I-3-27: Column chromatography PE:EA=2:1, 0.5% TEA gave a light yellow amorphous solid (yield 45%). 1H NMR (400MHz, CDCl3): δ7.71(d,J=9.1Hz,3H),7.43(d,J=8.4Hz,1H),7.12(ddd,J=15.9,12.3,3.8Hz,3H),6.89(dd,J=5.1,3.4Hz,1H),6 .73(d,J=3.3Hz,1H),6.56(s,1H),6.48(s,1H),5.98(d,J=9.7Hz,1H),5.65(dd,J=55.3,1.5Hz,2H),5.04(s,1H),3.91(s,3H),3.75(s,1 H),3.64(s,3H),3.51(s,1H),3.17–3.04(m,2H),2.98–2.80(m,2H),2.65–2.48(m,3H),2.37(dd,J=14.1,6.7Hz,1H),2.28(d,J=15.3Hz ,1H),2.00(dd,J=12.9,8.9Hz,1H),1.95–1.81(m,4H),1.81–1.70(m,3H),1.63(d,J=7.2Hz,3H),1.57(s,3H)ppm.HRMS-ESI(m / z):Calcd for C 43 H 47 N2O9S[M+H] + 767.2999.Found 767.2964. Compound I-3-28: Column chromatography PE:EA=2:1, 0.5% TEA gave a light yellow amorphous solid (yield 31%). 1H NMR (400MHz, CDCl3): δ7.68–7.62(m,3H),7.38(dd,J=8.4,1.8Hz,1H),7.14–7.03(m,3H),6.86(dd,J=5.2,3.4Hz,1H),6.60(d,J=3.7Hz,1H),6.50 (s,1H),6.49(s,1H),5.97(d,J=9.5Hz,1H),5.73(dd,J=53.8,1.6Hz,2H) ,5.08(s,1H),3.89(s,3H),3.76(d,J=9.4Hz,1H),3.66(s,3H),3.53–3.43 (m,1H),3.14–3.02(m,2H),2.92(dd,J=11.2,7.0Hz,1H),2.87(s,1H),2. 65–2.53(m,3H),2.52(d,J=14.1Hz,1H),2.36–2.22(m,2H),2.02–1.98(m ,1H),1.91(td,J=12.4,11.9,5.2Hz,2H),1.78(s,3H),1.77–1.73(m,2H),1.70(d,J=14.1Hz,2H),1.63(d,J=7.1Hz,3H)ppm.HRMS-ESI(m / z):Calcd for C 43 H 47 N2O9S[M+H] + 767.2999.Found 767.2964. Compound I-3-29: Column chromatography PE:EA=2:1, 0.5% TEA gave a light yellow amorphous solid (yield 40%). 1H NMR (400MHz, CDCl3): δ7.70(d,J=8.9Hz,2H),7.42(d,J=8.6Hz,1H),7.17–7.08(m,2H),6.94(s,1H),6.83(d,J=7.9Hz,1H),6.67(d,J=8.1Hz,1H),6. 52(d,J=16.3Hz,2H),5.96(d,J=9.7Hz,1H),5.71(s,1H),5.54(s,1H),5.0 6(s,1H),4.53(t,J=8.6Hz,2H),3.91(s,3H),3.76(d,J=9.8Hz,1H),3.66( s,3H),3.40(s,1H),3.15(t,J=8.7Hz,2H),3.12–3.02(m,2H),2.91(td,J= 11.6,7.0Hz,1H),2.63–2.55(m,2H),2.53–2.42(m,1H),2.35(dd,J=14.3, 6.9Hz,1H),2.29(d,J=15.0Hz,1H),2.26–2.14(m,1H),2.00(s,2H),1.94– 1.70(m,6H),1.63(d,J=7.1Hz,3H),1.59(s,3H)ppm.HRMS-ESI(m / z):Calcd for C 47 H 51 FN2O 10 [M+H] + 803.3542.Found 803.3465. Compound I-3-30: Column chromatography PE:EA=2:1, 0.5% TEA to obtain a light yellow amorphous solid (yield 20%). 1H NMR (400MHz, CDCl3): δ7.64(d,J=8.8Hz,2H),7.58(d,J=8.5Hz,1H),7.34(d,J=8.3Hz,1H),7.09(d,J=9.0Hz,1H),7.04(s,1H),6.81(s,1H),6.73(d ,J=8.2Hz,1H),6.66(t,J=7.2Hz,1H),6.50(dd,J=12.3,2.5Hz,2H),5.98 (d,J=9.5Hz,2H),5.79(d,J=10.4Hz,1H),5.58(s,1H),5.10(s,1H),4.53( t,J=8.6Hz,2H),3.89(s,3H),3.78(d,J=9.7Hz,1H),3.69(s,3H),3.21–3 .05(m,4H),2.95–2.87(m,1H),2.85(s,1H),2.65–2.49(m,3H),2.32–2.20 (m,2H),2.07–1.97(m,2H),1.93–1.88(m,1H),1.82(s,3H),1.79–1.72(m,3H),1.72–1.64(m,2H),1.61(d,J=7.2Hz,3H)ppm.HRMS-ESI(m / z):Calcd for C 47 H 51 FN2O 10 [M+H] + 803.3542.Found 803.3465. Compound I-3-31 was purified by column chromatography with PE:EA=2:1, 0.5% TEA to obtain a light yellow amorphous solid (yield 20%). 1H NMR (400MHz, CDCl3): δ7.71(d,J=8.2Hz,3H),7.44(d,J=8.5Hz,1H),7.14(dd,J=13.0,4.1Hz,2H),7.01(dd,J=8.9,3.8Hz,1H),6.51(d,J=10 .7Hz,2H),5.93–5.88(m,1H),5.52(d,J=22.8Hz,2H),5.05(s,1H),3.9 1(s,3H),3.77–3.72(m,1H),3.65(s,3H),3.12–2.98(m,3H),2.89(td, J=11.4,6.9Hz,1H),2.57(q,J=8.5Hz,2H),2.30(td,J=14.8,7.8Hz,2H),2.08–1.95(m,1H),1.94–1.82(m,1H),1.74(ddd,J=18.9,12.4,5.4H z,4H),1.61(d,J=7.1Hz,3H),1.50(ddd,J=49.4,13.4,6.0Hz,3H),0.94–0.86(m,2H),0.83(dd,J=6.7,3.1Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 41 H 49 N2O9[M+H] + 713.3439.Found 713.3360. Compound I-3-32: Column chromatography PE:EA=4:1, 0.5% TEA gave a light yellow amorphous solid (yield 54%). 1H NMR (400MHz, CDCl3): δ7.71(d,J=8.2Hz,3H),7.44(d,J=8.5Hz,1H),7.14(dd,J=13.0,4.1Hz,2H),7.01(dd,J=8.9,3.8Hz,1H),6.51(d,J=10 .7Hz,2H),5.93–5.88(m,1H),5.52(d,J=22.8Hz,2H),5.05(s,1H),3.9 1(s,3H),3.77–3.72(m,1H),3.65(s,3H),3.12–2.98(m,3H),2.89(td, J=11.4,6.9Hz,1H),2.57(q,J=8.5Hz,2H),2.30(td,J=14.8,7.8Hz,2H),2.08–1.95(m,1H),1.94–1.82(m,1H),1.74(ddd,J=18.9,12.4,5.4H z,4H),1.61(d,J=7.1Hz,3H),1.50(ddd,J=49.4,13.4,6.0Hz,3H),0.94–0.86(m,2H),0.83(dd,J=6.7,3.1Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 40 H 47 N2O9[M+H] + 699.3203.Found 699.3280. Compound I-3-33: Column chromatography PE:EA=2:1, 0.5% TEA gave a light yellow amorphous solid (yield 58%). 1H NMR (400MHz, CDCl3): δ7.71(d,J=8.6Hz,3H),7.43(dd,J=8.4,1.8Hz,1H),7.18–7.06(m,3H),7.00(dd,J=8.6,4.0Hz,1H),6.89 (dd,J=5.1,3.4Hz,1H),6.75–6.71(m,1H),6.52(d,J=4.7Hz,2H),5.96(d,J=9.6Hz,1H),5.46(dd,J=46.8,1.5Hz,2H),5.08(s, 1H),3.92(s,3H),3.77(d,J=9.6Hz,1H),3.67(s,3H),3.14–3.00(m,3H),2.88(ddt,J=17.7,13.6,5.8Hz,2H),2.62–2.52(m,3H ),2.39–2.25(m,2H),2.09–1.95(m,2H),1.98–1.82(m,3H),1.84–1.70(m,3H),1.61(d,J=7.1Hz,3H)ppm.HRMS-ESI(m / z):Calcd for C 42 H 45 N2O9S[M+H] + 753.2845.Found 753.2768. Compound I-3-34: Column chromatography PE:EA=2:1, 0.5% TEA gave a light yellow amorphous solid (yield 83%). 1H NMR (400MHz, CDCl3): δ7.71(d,J=8.6Hz,3H),7.43(dd,J=8.3,1.9Hz,1H),7.16–7.10(m,2H),7.04(dd,J=8.7,4.0Hz,1H),6.95(s,1H),6.84(d, J=8.8Hz,1H),6.67(d,J=8.1Hz,1H),6.53(s,1H),6.51(s,1H),5.95(d,J=9.6Hz,1H),5.48(dd,J=48.8,1.6Hz,2H),5.09(s,1H),4.53(t,J=8.7 Hz,2H),3.92(s,3H),3.79(d,J=9.7Hz,1H),3.69(s,3H),3.16(t,J=8.7 Hz,2H),3.11–3.02(m,2H),3.08(s,1H),2.90(td,J=11.5,6.8Hz,1H),2 .64–2.47(m,4H),2.36–2.20(m,4H),2.09–1.97(m,1H),1.93–1.85(m,1H),1.82–1.71(m,4H),1.61(d,J=7.1Hz,3H)ppm.HRMS-ESI(m / z):Calcd for C 46 H 49 N2O 10 [M+H] + 789.3385.Found 789.3309. Example 24: Preparation of Ketoximine Ether Compounds General procedure: Under Ar atmosphere, add isopentyl bromide (1.2 mmol) dropwise to a DMF (2 mL) solution of oxime (1 mmol) containing K2CO3 (2 mmol), and monitor the reaction on a TLC plate until it is complete. Add saturated NaHCO3 to quench, extract with Et2O, combine the organic phases, wash with H2O and saturated NaCl in turn, and dry with anhydrous Na2SO4. Remove the solvent by rotary evaporation to obtain a crude ketoxime ether. Referring to the above method, the following compound was obtained: Compound I-3-35: Column chromatography PE:EA=7:1, 0.5% TEA gave a light yellow amorphous solid (yield 63%). 1H NMR (400MHz, CDCl3): δ6.59 (s, 1H), 6.55 (s, 1H), 5.93 (d, J = 9.0Hz, 1H), 5.85 (dd, J = 9.2, 1.6Hz, 2H), 5.02 (s, 1H), 3.76 (d, J = 9. 8Hz,1H),3.72(s,1H),3.66(s,3H),3.21–3.10(m,1H),3.13–3.02(m,1H),2.92(td,J=11.6,7.1Hz,1H),2.63–2.52(m,2H),2.37 (dd,J=14.1,6.9Hz,1H),2.11–1.96(m,3H),1.94–1.82(m,2H),1.74(ddd,J=17.1,8.7,4.6Hz,3H),1.61(s,3H),1.54–1.35(m, 3H),1.34–1.22(m,5H),1.13(dt,J=13.1,6.9Hz,1H),0.90–0.86(m,3H),0.83(dt,J=6.6,3.4Hz,8H)ppm.HRMS-ESI(m / z):Calcd for C 33 H 49 N2O7[M+H] + 585.3541.Found 584.3462. General procedure: Under Ar atmosphere, add isopentyl bromide (1.2 mmol) dropwise to a DMF (2 mL) solution of oxime (1 mmol) containing NaH (1.2 mmol), and monitor the reaction on a TLC plate until it is complete. Add half-saturated NH4Cl to quench, extract with Et2O, combine the organic phases, wash with H2O and saturated NaCl in turn, and dry with anhydrous Na2SO4. Remove the solvent by rotary evaporation to obtain a crude aldoxime ether. Compound I-3-36: Column chromatography PE:EA=6:1, 0.5% TEA gave a light yellow amorphous solid (yield 66%). 1H NMR (400MHz, CDCl3): δ6.57(d,J=4.4Hz,2H),6.23(dd,J=6.7,3.5Hz,1H),5.92(d,J=9.7Hz,1H),5.87(s,2H),5.06(s,1H),4.07(td,J =7.0,2.2Hz,2H),3.79(d,J=9.7Hz,1H),3.68(s,3H),3.15–3.06(m,2H),3.01(s,1H),2.98–2.89(m,1H),2.60(t,J=8.3Hz,2H),2.50( dd,J=16.7,6.7Hz,1H),2.37(dd,J=14.1,6.7Hz,1H),2.03(t,J=10.4Hz,1H),1.90(ddd,J=12.2,8.1,4.1Hz,1H),1.79–1.59(m,6H),1 .49(dq,J=37.9,6.8Hz,6H),0.93(dd,J=6.7,2.2Hz,6H),0.89(d,J=6.7Hz,1H),0.84(dd,J=6.6,2.2Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 32 H 47 N2O7[M+H] + 571.3384.Found 570.3305. Compound I-3-37: Column chromatography PE:EA=6:1, 0.5% TEA gave a light yellow amorphous solid (yield 35%). 1H NMR (400MHz, CDCl3) δ6.60(s,1H),6.58(s,1H),5.93(d,J=9.8Hz,1H),5.86(d,J=13.8Hz,2H),5.05(s,1H),4.20–4.01 (m,1H),3.99(t,J=7.0Hz,2H),3.79(d,J=9.6Hz,1H),3.67(s,3H),3.19–3.04(m,2H),2.94(dd,J=21.0,9.1Hz,1H),2. 64–2.53(m,2H),2.38(dd,J=13.7,6.7Hz,1H),2.15–1.97(m,2H),1.95–1.84(m,1H),1.83–1.69(m,3H),1.70–1.39(m, 5H),1.27(h,J=8.6,7.5Hz,6H),1.16–0.98(m,1H),0.90(d,J=6.8Hz,6H),0.89–0.80(m,3H)ppm.HRMS-ESI(m / z):Calcd forC 31 H 45 N2O7[M+H] + 557.3225.Found 557.3149. Compound I-3-38: Column chromatography PE:EA=3:1, 0.5% TEA gave a light yellow amorphous solid (yield 40%). 1 H NMR (400MHz, CDCl3): δ7.10(dd,J=5.2,1.2Hz,1H),6.90(dd,J=5.2,3.4Hz,1H),6.74(d,J=2.2Hz,1H),6.58(s,1H),6.58(s,1H ),6.23(dd,J=6.7,3.6Hz,1H),5.98(d,J=9.6Hz,1H),5.83(dd,J=26.4,1.7Hz,2H),5.09(s,1H),4.07(td,J=7.0,2.4Hz,2H),3 .82(d,J=9.7Hz,1H),3.70(s,3H),3.19–3.05(m,3H),3.01–2.80(m,2H),2.66–2.49(m,4H),2.38(dd,J=14.2,6.8Hz,1H),2.12 –1.99(m,1H),1.97–1.85(m,3H),1.81–1.72(m,3H),1.73–1.61(m,3H),0.91(dd,J=6.6,4.0Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C33 H 43 N2O7S[M+H] + 611.2789.Found 611.2713. Example 25: Preparation of Carbamate Oxime Ester Compounds General procedure: Under Ar atmosphere, cyclopentylcarbamate (1.2 mmol) was added dropwise to a solution of oxime (1 mmol) in CH2Cl2 (2 mL) and the reaction was continued for 12 h. Saturated NaHCO3 was added to quench the reaction, and the mixture was extracted with CH2Cl2. The organic phases were combined, washed with saturated NaCl, and dried over anhydrous Na2SO4. The solvent was removed by rotary evaporation to obtain the crude product of carbamate oxime ester. Referring to the above method, the following compound was obtained: Compound I-3-39: Column chromatography PE:EA=6:1, 0.5% TEA gave a light yellow amorphous product (yield 32%). 1 H NMR (400MHz, CDCl3): δ6.49(s,1H),6.42(s,1H),6.07(d,J=7.2Hz,1H),5.96(d,J=9.7Hz,1H),5.88(d,J=1.6Hz,2H),5.05(s,1H), 4.09(h,J=6.9Hz,1H),3.71(d,J=9.3Hz,1H),3.67(s,3H),3.30(s,1H),3.18–3.00(m,2H),2.90(td,J=11.5,7.0Hz,1H),2.63–2.51 (m,2H),2.34(dd,J=14.1,7.0Hz,1H),2.27(d,J=17.5Hz,1H),2.13(d,J=17.5Hz,1H),2.11–1.93(m,4H),1.96–1.83(m,2H),1.85–1 .74(m,2H),1.74(s,3H),1.72–1.51(m,6H),1.52–1.42(m,2H),1.41–1.28(m,1H),0.86(d,J=6.6Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 34 H 48 N3O8[M+H] + 626.3438.Found 626.3363. Compound I-3-40: Column chromatography PE:EA=6:1, 0.5% TEA gave a light yellow amorphous solid (yield 41%). 1H NMR (400MHz, CDCl3): δ6.68(s,1H),6.63(s,1H),6.21(d,J=7.4Hz,1H),5.97(d,J=9.6Hz ,1H),5.85(s,2H),5.08(s,1H),4.08(h,J=6.8Hz,1H),3.85(d,J=9.7Hz,1H),3.69(s,3H) ,3.21–2.99(m,4H),2.75–2.55(m,3H),2.13–1.89(m,6H),1.79(s,3H),1.73–1.53(m,6H ),1.55–1.41(m,3H),1.43–1.30(m,4H),0.82(d,J=6.6Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 34 H 48 N3O8[M+H] + 626.3438.Found 626.3363. Compound (I-3-41): Column chromatography PE:EA=6:1, 0.5% TEA gave a light yellow amorphous solid (yield 32%). 1 H NMR (400MHz, CDCl3): δ6.48(s,1H),6.42(s,1H),6.03(d,J=1.7Hz,1H),5.97(d,J=9.7Hz,1H),5.86(d,J=1.7Hz,1H),5.86–5.68 (m,1H),5.06(s,1H),5.05–4.90(m,2H),4.17–4.04(m,1H),3.69(d,J=10.1Hz,1H),3.67(s,3H),3.31(d,J=1.5Hz,1H),3.18–3. 01(m,3H),2.97–2.85(m,1H),2.63–2.52(m,2H),2.34(dd,J=13.6,6.3Hz,1H),2.30(d,J=17.3Hz,1H),2.24–2.15(m,1H),2.18( d,J=17.3Hz,1H),2.13–1.87(m,6H),1.85–1.76(m,2H),1.76(s,3H),1.75(s,1H),1.72–1.52(m,6H)ppm.HRMS-ESI(m / z):Calcd for C 33 H 44 N3O8[M+H] + 610.3126.Found 610.3050. Compound I-3-42: Column chromatography PE:EA=6:1, 0.5% TEA gave a light yellow amorphous solid (yield 42%). 1 H NMR (400MHz, CDCl3): δ6.48(s,1H),6.42(s,1H),6.03(s,1H),5.97(d,J=9.7Hz,1H),5.86(s,1H),5.85–5.68(m,1H), 5.05(s,1H),5.04–4.88(m,2H),4.08(dd,J=8.4,4.9Hz,1H),3.69(d,J=10.1Hz,1H),3.67(s,3H),3.41–3.27(m,1H), 3.18–2.99(m,2H),2.98–2.81(m,1H),2.64–2.52(m,3H),2.40–2.25(m,2H),2.18(d,J=17.3Hz,2H),2.12–1.94(m,4H ),1.96–1.84(m,2H),1.87–1.75(m,2H),1.75(s,3H),1.76–1.69(m,1H),1.73–1.54(m,6H)ppm.HRMS-ESI(m / z):Calcd for C 33 H 44 N3O8[M+H] + 610.3126.Found 610.3050. Compound I-3-43: Column chromatography PE:EA=3:1, 0.5% TEA gave a light yellow amorphous solid (yield 21%). 1H NMR (400MHz, CDCl3): δ7.09(dd,J=5.2,1.2Hz,1H),6.89(dd,J=5.2,3.4Hz,1H),6.73(d,J=3.4Hz,1H),6.68(s,1H),6.63(s,1H),6.17(d ,J=7.4Hz,1H),6.01(d,J=9.6Hz,1H),5.80(dd,J=14.1,1.5Hz,2H),5.09(s,1H),4.07(h,J=7.3Hz,1H),3.86(d,J=9.6Hz,1H),3.67(s,3 H),3.23(s,1H),3.17–3.07(m,2H),2.94(td,J=11.6,6.8Hz,1H),2.89–2.76(m,1H),2.67(d,J=14.2Hz,1H),2.66–2.53(m,3H),2.06–1. 86(m,5H),1.81(s,3H),1.74(dd,J=13.1,4.7Hz,2H),1.71–1.55(m,6H),1.53–1.40(m,2H),1.43–1.31(m,1H)ppm.HRMS-ESI(m / z):Calcd for C 35 H 44 N3O8S[M+H] + 666.2680.Found 666.2771. Compound I-3-44: Column chromatography PE:EA=3:1, 0.5% TEA gave a light yellow amorphous solid (yield 18%). 1H NMR (400MHz, CDCl3): δ7.11(dd,J=5.1,1.2Hz,1H),6.92(dd,J=5.2,3.4Hz,1H),6.76(d,J=2.2Hz,1H),6.49(s,1H),6.44(s,1H),6.06( d,J=7.2Hz,1H),6.02(d,J=1.7Hz,1H),5.86(d,J=1.7Hz,1H),5.07(s,1H),4.10(h,J=6.8Hz,1H),3.72(d,J=9.7Hz,1H),3.65(s,3H),3 .41(d,J=1.6Hz,1H),3.18–3.01(m,2H),3.02–2.87(m,2H),2.70(td,J=13.6,4.6Hz,1H),2.62–2.55(m,2H),2.35(dd,J=14.4,7.0Hz,1 H),2.22(d,J=17.5Hz,1H),2.20(d,J=17.5Hz,1H),2.11–1.95(m,4H),1.98–1.85(m,3H),1.86–1.78(m,2H),1.77(s,3H),1.73–1.55(m 6H)ppm.HRMS-ESI(m / z):Calcd for C 35 H 44 N3O8S[M+H] + 666.2680.Found 666.2771. Compound I-3-45: Column chromatography PE:EA=3:1, 0.5% TEA gave a light yellow amorphous solid (yield 44%). 1H NMR (400MHz, CDCl3): δ6.94(s,1H),6.83(d,J=8.1Hz,1H),6.66(d,J=8.1Hz,1 H),6.66(s,1H),6.62(s,1H),6.17(d,J=7.4Hz,1H),6.00(d,J=9.6Hz,1H),5.7 8(dd,J=22.7,1.6Hz,2H),5.11(s,1H),4.53(t,J=8.6Hz,2H),4.06(q,J=6.9H z,1H),3.86(d,J=9.7Hz,1H),3.70(s,3H),3.20(s,1H),3.16(t,J=8.5Hz,2H), 3.15–3.04(m,2H),2.94(td,J=11.5,6.9Hz,1H),2.70(d,J=14.1Hz,1H),2.60 (td,J=14.5,6.9Hz,3H),2.49(td,J=12.8,4.7Hz,1H),2.24(td,J=13.7,13.2, 3.9Hz,1H),2.10–1.95(m,2H),1.91(dt,J=8.4,5.2Hz,2H),1.82(s,3H),1.82 –1.71(m,2H),1.72–1.54(m,6H),1.53–1.40(m,3H)ppm.HRMS-ESI(m / z):Calcd for C 39 H 48 N3O9[M+H] + 702.3388.Found 702.3312. Compound I-3-46: Column chromatography PE:EA=6:1, 0.5% TEA gave a light yellow amorphous solid (yield 38%). 1H NMR (400MHz, CDCl3): δ6.64(s,1H),6.60(s,1H),5.94(d,J=9.7Hz,1H),5.91–5.88(m,2H),5.09(s,1H),3.81( d,J=9.7Hz,1H),3.68(s,4H),3.34(s,1H),3.13–3.01(m,2H),3.01–2.89(m,2H),2.66–2.54(m,2H),2.38(dd, J=13.6,6.3Hz,1H),2.10–2.01(m,2H),2.00–1.85(m,2H),1.80–1.71(m,4H),1.67–1.53(m,4H),1.47(dt,J=1 3.2,6.5Hz,1H),1.40–1.23(m,4H),0.97–0.88(m,3H),0.85(dd,J=6.6,4.5Hz,6H)ppm.HRMS-ESI(m / z):Calcd for C 33 H 46 N3O8[M+H] + 612.3286.Found 612.3207. Example 26: In vitro biological activity test Test cells Human breast cancer cells MCF-7, liver cancer cells HepG2, and lung adenocarcinoma cells A549 were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences. Human leukemia cells HL-60, human leukemia cell adriamycin-resistant strain HL-60 / ADR, and human glioblastoma cells U-87MG were purchased from Shanghai Chuanqiu Biotechnology Co., Ltd. Human cervical cancer HeLa was purchased from Shanghai Jikai Gene Chemistry Technology Co., Ltd. Human colon cancer cells HCT-116 and human brain microvascular endothelial cells hCMEC / D3 were preserved by Tianjin Suntech Pharmaceutical Technology Co., Ltd. Human colon cancer cells Sw620 and human colon cancer cells LoVo were provided by the Affiliated Hospital of Tianjin Medical University. Main instruments and consumables Carbon dioxide constant temperature cell culture incubator, Thermo Fisher, USA; Inverted biological microscope, Chongqing Aote Optical Instrument Co., Ltd.; Microplate reader, Thermo Fisher, USA; Precision adjustable micropipette, Eppendorf (Germany); 96-well cell culture plate, Wuxi Nice Life Science Co., Ltd.; Cell culture dish, Wuxi Nice Life Science Co., Ltd. Main reagents Fetal bovine serum, BI, Israel; Trypsin, Gibco; Bispecific antibodies, Gibco; DMEM medium, BI, Israel; DMSO, Tianjin Bohai Chemical Reagent Co., Ltd.; MTT, Shanghai Yuanye Biotechnology Co., Ltd. The experimental steps are as follows: Cell culture Human breast cancer cells MCF-7, liver cancer cells HepG2, lung adenocarcinoma cells A549, human leukemia cells HL-60, human leukemia cells adriamycin-resistant strain HL-60 / ADR, human glioblastoma cells U-87MG, human cervical cancer cells HeLa, human colon cancer cells HCT-116, human colon cancer cells Sw620, human colon cancer cells LoVo, human brain microvascular endothelial cells HCMEC / D3 were cultured using DMEM medium. The culture medium was a culture medium in which 10% fetal bovine serum and 1% double antibody (penicillin + streptomycin) were added, and the culture environment was a culture box filled with 5% CO2 and a temperature of 37°C; when the cells basically covered the bottom of the dish (about 80%-90%), subculture was performed. Prepare working fluid Preparation of MTT solution: Weigh 50 mg of MTT, dissolve in 10 mL of phosphate buffered saline (PBS), divide into aliquots, and store at 4°C away from light. It is valid within two weeks. Preparation of test drugs: Take a series of compounds and dilute them with culture medium to prepare 1 mg / ml stock solution. Before use, accurately pipette an appropriate amount of sample stock solution and dilute it with culture medium to prepare working solutions with different concentration gradients, such as 100μg / ml, 10μg / ml, 1μg / ml, 0.1μg / ml, 0.01μg / ml, 0.001μg / ml, etc. Determination method 1. Take the cells in the logarithmic phase, digest, centrifuge and resuspend. Add culture medium to adjust the cell density to 1×10 5 100 μL of the prepared cell suspension was added to each well and inoculated into a 96-well cell culture plate, which was then placed in a cell culture incubator for culture. 2. After 24 hours of culture, 2 μl of a series of compounds with concentrations of 100 μg / ml, 10 μg / ml, 1 μg / ml, 0.1 μg / ml, 0.01 μg / ml, and 0.001 μg / ml were added to the test groups, with 4 replicate wells for each concentration, and a positive control group (etoposide) and a blank control group were set up. 3. After culturing the 96-well plate for 48 hours, add 20 μl of MTT solution (concentration of 5 mg / ml) to each well and continue culturing in the incubator for 4 hours. 4. Take the 96-well plate out of the incubator, carefully aspirate the culture medium in the wells with a micropipette, add 150 μl of dimethyl sulfoxide to each well, shake to completely dissolve the crystals, and then use a microplate reader to measure the absorbance OD value at a wavelength of 492 nm. 5. The test was repeated three times, and the cell inhibition rate was calculated according to the following formula: Cell inhibition rate (%) = [1-OD value of the test group / OD value of the blank control group)] × 100%, and the half inhibitory concentration IC of the sample to inhibit cell growth was calculated 50 value. The experimental results show that the effect of DMSO solvent below 0.1v% on cells is negligible, and IC 50 The experimental results are summarized in Table 1. Table 1: Activity data of the compounds in the examples (IC 50 (nM) The above is a description of the exemplary embodiments of the present invention. However, the protection scope of the present invention is not limited to the above embodiments. Any modification, equivalent replacement or improvement made by a person skilled in the art within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A compound represented by formula (I), its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound: in, R S Selected from (R N ) m -G-(CH2) n -or (R Q ) m -G-(CH2) n -: R N represents a substituent containing a nitrogen atom, such as nitro, unsubstituted or optionally substituted with one, two or more R a Substituted with the following groups: -NR 6 R 7 、-NR 6’ -C(=YR 4 )-NR 6 R 7 ; Every R 6 , R 6’ and R 7 are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R b Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, R 10 C(=O)-、R 10 C(=O)O-、R 10 C(=O)NH-、R 10 OC(=O)-、R 10 NHC(=O)-、R 10 S(O)2-、R 10 S(O)2O-、R 10 OS(O)2-、R 10 S(O)-, three(C 1-20 Alkyloxy)silyl C 1-20 Alkyl, tri(C 1-20 Alkyl)silyl; R Q represents H, halogen, -OH, -CN, unsubstituted or optionally substituted with one, two or more R c Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, R 10 C(=O)-、R 10 C(=O)O-、R 10 OC(=O)-、R 10 S(O)2-、R 10 S(O)2O-、R 10 OS(O)2-、R 10 S(O)-, three(C 1-20 Alkyloxy)silyl C 1-20 Alkyl, tri(C 1-20 Alkyl)silyl; G represents chemical bond, C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl; provided that when G is not a chemical bond, the positions on G substituted by different groups connected to G may be separated by 1-10 atoms, such as 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 atoms; for example, when G is phenyl, the positions on G substituted by different groups connected to it may be separated by 1, 2, 3, 4 or 5 carbon atoms, for example, the different groups are substituted at the ortho position, meta position and / or para position on G, preferably meta position and / or para position; Each m is the same or different and is independently selected from an integer greater than 1; Each n is the same or different and is independently selected from an integer greater than 1; Each Y is the same or different and is independently selected from O, S or N, provided that when Y is selected from O or S, R 4 does not exist; R 1 and R 2 The same or different, independently selected from H, C 1-6 Alkyl or halogen; R 3 Selected from R 8 , R 8 -O-、R 8 -S-; R 4 is absent, or is selected from H, unsubstituted or optionally substituted with one, two or more R d Substituted with the following groups: R 8 -O-、R 8 -S-、R 9 C(=O)O-、R 10 OC(=O)O-、R 10 NHC(=O)-、R 10 NHC(=O)O-、R 10 C(=O)NH-; R 5 Select from H or C 1-6 alkyl; Every R a , R b , R c and R d are the same or different, independently selected from halogen, -OH, -CN, -NO2, oxo (=O), unsubstituted or optionally substituted by one, two or more R e Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, R 11 C(=O)-、R 11 C(=O)O-、R 11 C(=O)NH-、R 11 OC(=O)-、R 11 NHC(=O)-、R 11 S(O)2-、R 11 S(O)2O-、R 11 OS(O)2-、R 11 S(O)-、-NR 12 R 13 、-NH-C(=Y)-NR 12 R 13 , three (C 1-20 Alkyloxy)silyl C 1-20 Alkyl, tri(C 1-20 Alkyl)silyl; Every R 8 , R 9 , R 10 and R 11 The same or different, independently selected from H, C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, R 11’ C(=O)-、R 11’ C(=O)O-、R 11’ C(=O)NH-、R 11’ OC(=O)-、R 11’ NHC(=O)-、R 11’ S(O)2-、R 11’ S(O)2O-、R 11’ OS(O)2-、R 11’ S(O)-、-NR 12 R 13 、-NH-C(=Y)-NR 12 R 13 , three (C 1-20 Alkyloxy)silyl C 1-20 Alkyl, tri(C 1-20 Alkyl)silyl; Every R 11’ , R 12 and R 13 are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R f Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl; Every R e and R f are the same or different, independently selected from halogen, -OH, -CN, -NO2, -NH2, oxo (=O), unsubstituted or optionally substituted by one, two or more R g Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio, R 14 C(=O)-、R 14 C(=O)O-、R 14 OC(=O)-、R 14 S(O)2-、R 14 S(O)2O-、R 14 OS(O)2-、R 14 S(O)-; Every R 14 The same or different, independently selected from C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl; Every R g are the same or different and are independently selected from halogen, -OH, -CN, -NO2, -NH2, oxo (=O), C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, C 1-20 Alkyloxy, C 2-20 Alkenyloxy, C 3-20 Cycloalkyloxy, C 3-20 Cycloalkenyloxy, 3-20 membered heterocyclyloxy, C 6-20 Aryloxy, 5-20 membered heteroaryloxy, C 1-20 Alkylthio, C 2-20 Alkenylthio, C 3-20 Cycloalkylthio, C 3-20 Cycloalkenylthio, 3-20 membered heterocyclylthio, C 6-20 Arylthio, 5-20 membered heteroarylthio; Optionally, the C 3-20 One, two or more carbon atoms of the cycloalkyl or 3-20 membered heterocyclic group may be optionally substituted with oxygen to form a carbonyl group.

2. The compound of claim 1, its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound, wherein: G represents chemical bond, C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, such as chemical bonds, C 1-8 Alkyl, C 2-8 alkenyl, phenyl, naphthyl; m represents an integer of 1 to 20, preferably an integer of 1 to 10; n represents an integer of 1 to 20, preferably an integer of 1 to 10; Halogen represents F, Cl, Br or I; Y is selected from O, N or S; R 3 Selected from H, C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, C 1-8 Alkyl-O-, C 2-8 Alkenyl-O-, C 3-15 Cycloalkyl-O-, C 3-15 Cycloalkenyl-O-, 3-15 membered heterocyclyl-O-, C 6-15 Aryl-O-, 5-15 membered heteroaryl-O-, C 1-8 Alkyl-S-, C 2-8 Alkenyl-S-, C 3-15 Cycloalkyl-S-, C 3-15 Cycloalkenyl-S-, 3-15 membered heterocyclyl-S-, C 6-15 Aryl-S-, 5-15 membered heteroaryl-S-; R 4 Not present or selected from H; R N represents nitro, unsubstituted or optionally substituted with one, two or more R a Substituted with the following groups: -NR 6 R 7 、-NH-C(=YR 4 )-NR 6 R 7 ; Preferably, R N Selected from -NR 6 R 7 、-NH-C(=O)-NR 6 R 7 、-NH-C(=S)-NR 6 R 7 or -NH-C(=NH)-NR 6 R 7 ; Or, R N is selected from nitro, amino, or phenyl substituted by nitro or amino at the ortho, meta and / or para positions, wherein the amino group is unsubstituted or substituted by one, two or more selected from C 1-8 Alkylcarbonyl, C 1-8 Alkyloxycarbonyl, C 3-8 Cycloalkylcarbonyl, C 3-8 Cycloalkyloxycarbonyl, C 6-10 Arylcarbonyl, C 6-10 Aryloxycarbonyl, C 2-8 The substituents of the alkenyl group are substituted.

3. The compound according to claim 1 or 2, its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound, wherein: R 6 is selected from H, unsubstituted or optionally substituted with one, two or more R b Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, R 10 C(=O)-、R 10 C(=O)O-、R 10 OC(=O)-、R 10 S(O)2-、R 10 S(O)2O-、R 10 OS(O)2-、R 10 S(O)-, three(C 1-20 Alkyloxy)silyl C 1-20 Alkyl, tri(C 1-20 Alkyl)silyl; R 7 is selected from H, unsubstituted or optionally substituted with one, two or more R b Substituted with the following groups: C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl, R 10 C(=O)-、R 10 C(=O)O-、R 10 OC(=O)-、R 10 S(O)2-、R 10 S(O)2O-、R 10 OS(O)2-、R 10 S(O)-, three(C 1-20 Alkyloxy)silyl C 1-20 Alkyl, tri(C 1-20 Alkyl)silyl. Preferably, R 6 is selected from H, unsubstituted or optionally substituted with one, two or more R b Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, R 10 C(=O)-、R 10 C(=O)O-、R 10 OC(=O)-、R 10 S(O)2-、R 10 S(O)2O-、R 10 OS(O)2-、R 10 S(O)-, three(C 1-8 Alkyloxy)silyl C 1-8 Alkyl, tri(C 1-8 Alkyl)silyl; R 7 is selected from H, unsubstituted or optionally substituted with one, two or more R b Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, R 10 C(=O)-、R 10 C(=O)O-、R 10 OC(=O)-、R 10 S(O)2-、R 10 S(O)2O-、R 10 OS(O)2-、R 10 S(O)-, three(C 1-8 Alkyloxy)silyl C 1-8 Alkyl, tri(C 1-8 Alkyl)silyl; R 10 Selected from C 1-8 Alkyl, C 2-8 Alkenyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, 3-8 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, NH2; Every R a and R b are the same or different and are independently selected from halogen, -OH, -CN, -NO2, unsubstituted or optionally substituted by one, two or more R d Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, C 1-8 Alkyloxy, C 2-8 Alkenyloxy, C 3-15 Cycloalkyloxy, C 3-15 Cycloalkenyloxy, 3-15 membered heterocyclyloxy, C 6-15 Aryloxy, 5-15 membered heteroaryloxy, C 1-8 Alkylthio, C 2-8 Alkenylthio, C 3-15 Cycloalkylthio, C 3-15 Cycloalkenylthio, 3-15 membered heterocyclylthio, C 6-15 Arylthio, 5-15 membered heteroarylthio, R 11 C(=O)-、R 11 C(=O)O-、R 11 OC(=O)-、R 11 S(O)2-、R 11 S(O)2O-、R 11 OS(O)2-、R 11 S(O)-、-NR 12 R 13 、-NH-C(=Y)-NR 12 R 13 ; Three (C 1-20 Alkyloxy)silyl C 1-20 alkyl; Preferably, R 7 selected from, for example, H, unsubstituted or optionally substituted with one, two or more R e Substituted with the following groups: C 1-8 Alkyl, C 3-8 Cycloalkyl, C 2-8 Alkenyl, tri(C 1-8 Alkyloxy)silyl C 1-8 Alkyl, phenyl, biphenyl, naphthyl; For example, R 7 is selected from H, unsubstituted or optionally substituted with one, two or more R e Substituted from the following groups: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, allyl, phenyl, 4. The compound according to any one of claims 1 to 3, its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound thereof, wherein: R Q is selected from H, halogen, -OH, -CN, unsubstituted or optionally substituted with one, two or more R c Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, C 1-8 Alkyloxy, C 2-8 Alkenyloxy, C 3-15 Cycloalkyloxy, C 3-15 Cycloalkenyloxy, 3-15 membered heterocyclyloxy, C 6-15 Aryloxy, 5-15 membered heteroaryloxy, C 1-8 Alkylthio, C 2-8 Alkenylthio, C 3-15 Cycloalkylthio, C 3-15 Cycloalkenylthio, 3-15 membered heterocyclylthio, C 6-15 Arylthio, 5-15 membered heteroarylthio; Preferably, R Q is selected from H, halogen, -OH, -CN, unsubstituted or optionally substituted with one, two or more R c Substituted with the following groups: C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, for example unsubstituted or optionally substituted with one, two or more R c Substituted from the following: methyl, ethyl, propyl, isopropyl, vinyl, propenyl, allyl, trifluoromethyl-methyl, pentafluoroethyl, phenyl, naphthyl, thienyl, dihydrobenzofuranyl; R 3 Selected from H, C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, C 1-8 Alkyl-O-, C 2-8 Alkenyl-O-, C 3-15 Cycloalkyl-O-, C 3-15 Cycloalkenyl-O-, 3-15 membered heterocyclyl-O-, C 6-15 Aryl-O-, 5-15 membered heteroaryl-O-, C 1-8 Alkyl-S-, C 2-8 Alkenyl-S-, C 3-15 Cycloalkyl-S-, C 3-15 Cycloalkenyl-S-, 3-15 membered heterocyclyl-S-, C 6-15 Aryl-S-, 5-15 membered heteroaryl-S-; Preferably, R 3 is selected from H, methyl, methoxy, methylthio; Y is selected from N.

5. The compound according to any one of claims 1 to 3, its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound thereof, wherein: R Q is selected from H, unsubstituted or optionally substituted with one, two or more R c Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl; Preferably, R Q is selected from unsubstituted or optionally substituted with one, two or more R c Substituted with the following groups: C 1-6 Alkyl, C 2-6 Alkenyl, C 3-10 Cycloalkyl, C 3-10 Cycloalkenyl, 3-10 membered heterocyclic group, C 6-10 Aryl, 5-10 membered heteroaryl, for example unsubstituted or optionally substituted by one, two or more Multiple R c Substituted: methyl, ethyl, propyl, isopropyl, vinyl, propenyl, allyl, thienyl, dihydrobenzofuranyl; R 3 Selected from H, C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl; R 4 is selected from unsubstituted or optionally substituted with one, two or more R d Substituted with the following groups: R 8 -O-、R 8 -S-、R 9 C(=O)O-; Every R 8 and R 9 The same or different, independently selected from H, C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, -NR 12 R 13 ; Every R 12 and R 13 are the same or different and are independently selected from H, unsubstituted or optionally substituted with one, two or more R f Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl; Preferably, R 12 Selected from H, R 13 is selected from unsubstituted or optionally substituted with one, two or more R f Substituted with the following groups: C 1-8 Alkyl, C 2-8 Alkenyl, C 3-15 Cycloalkyl, C 3-15 Cycloalkenyl, 3-15 membered heterocyclic group, C 6-15 Aryl, 5-15 membered heteroaryl, -NR 12 R 13 , for example selected from cyclopentyl. Preferably, R 8 Selected from H, -OH, acryloyl, isobutyryl, isopentyl, R 9 Selected from C 1-8 Alkyl, C 2-8 Alkenyl, NH2.

6. The compound according to any one of claims 1 to 5, its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound, wherein the compound represented by formula (I) can be selected from the compounds represented by the following formula (I-1), (I-2), (I-3), (I-4) or (I-5): in, R 6 , R 6’ , R 7 , G, n, R 3 Independently selected from the definitions in any one of claims 1 to 5, Y represents O, S or NH; Among them, R Q , G, n, R 3 Independently selected from the definitions in any one of claims 1 to 5; Among them, R Q , G, n, R 3 , R 4 Independently selected from the definitions in any one of claims 1 to 5; Among them, R 6 , R 7 , G, n, R 3 Independently selected from the definitions in any one of claims 1 to 5; Among them, R 6 , R 10 , G, n, R 3 Independently of each other, the definitions are selected from any one of claims 1 to 5.

7. The compound according to claim 1, its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound thereof, wherein the compound represented by formula (I) is selected from the following compounds: in, Groups R, G, R 4 and n have the definitions described in the following table: Alternatively, the compound represented by formula (I) is selected from the following compounds: Among them, the groups R, R 3 and n have the definitions described in the following table: Alternatively, the compound represented by formula (I) is selected from the following compounds: Among them, the groups R, R 3 and R 8 Has the definitions described in the following table:

8. A method for preparing the compound of formula (I) according to any one of claims 1 to 7, its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound thereof, wherein the preparation method may include one selected from the following methods: Method (1) in, R 1 , R 2 , R 4 , R 5 , Y has the meaning given above; R 3 Selected from R 8 -O-; In step (1), a base and R 8 -OH to prepare a compound of formula (I); Method (2) When the substituent R of the compound of formula (I) S When it contains an amino group, the corresponding nitro compound is used as a substrate to reduce and prepare the compound of formula (I); Preferably, the reduction is carried out in the presence of Zn and AcOH; Method (3) When the substituent R of the compound of formula (I) S When the compound contains an acylamino group, the corresponding amino compound is used as a substrate to prepare the compound of formula (I) through an acylation reaction; Method (4) When the substituent R of the compound of formula (I) S When the urea group is contained, the corresponding amino compound is used as a substrate and reacted with an isocyanate compound to prepare the compound of formula (I); Methods (5) When the substituent R of the compound of formula (I) S When the guanidine group is contained, the corresponding amino compound is used as a substrate and reacted with nitrile amine, acyl nitrile amine or differently substituted carbodiimide compounds to prepare the compound of formula (I); Methods (6) Among them, R 1 , R 2 , R 3 , R 5 has the meaning given above; R 4 Selected from hydroxyl group; Y is selected from N; The step (1) is reacted in the presence of a base and hydroxylamine hydrochloride to prepare a compound of formula (I); Methods (7) Among them, R 1 , R 2 , R 3 , R 5 has the meaning given above; R 4 Selected from R 9 C(=O)O-; Y is selected from N; In step (1), a base and C 1-20 Alkyl-C(O)-OC(O)-C 1-20 The reaction is carried out in the presence of an alkyl group to prepare a compound of formula (I); Methods (8) Among them, R 1 , R 2 , R 3 , R 5 has the meaning given above; R 4 Selected from R 9 C(=O)O-; Y is selected from N; In step (1), a base and R 9 C(=O)Cl or R 9 The reaction is carried out in the presence of C(=O)OH to prepare a compound of formula (I); Methods (9) Among them, R 1 , R 2 , R 3 , R 5 has the meaning given above; R 4 Selected from R 8 -O-; R 8 Selected from C 1-20 Alkyl, C 2-20 Alkenyl, C 3-20 Cycloalkyl, C 3-20 Cycloalkenyl, 3-20 membered heterocyclic group, C 6-20 Aryl, 5-20 membered heteroaryl; Y is selected from N; In step (1), a base and R 8 -L to react to prepare a compound of formula (I); L is a leaving group, such as halogen, preferably Br or I; Methods (10) Among them, R 1 , R 2 , R 3 , R 5 has the meaning given above; R 4 Selected from R 10 NHC(=O)O-; Y is selected from N; The step (1) is performed in R 10 -N=C=O to prepare a compound of formula (I); Optionally, the preparation method further comprises the step of reacting the prepared compound of formula (I) with a pharmaceutically acceptable acid or base to form a salt.

9. A pharmaceutical composition comprising at least one of the compound of formula (I) according to any one of claims 1 to 7, its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound thereof.

10. Use of at least one of the compound of formula (I) according to any one of claims 1 to 7, its racemate, stereoisomer, tautomer, isotope-labeled substance, N-oxide, hydrate, solvate, polymorph, metabolite, pharmaceutically acceptable salt, pharmaceutically acceptable ester or prodrug compound thereof in the preparation of a medicament for preventing and / or treating a disease caused by uncontrolled cell growth, proliferation and / or survival, inappropriate cellular immune response or inappropriate cellular inflammatory response, or accompanied by uncontrolled cell growth, proliferation and / or survival, inappropriate cellular immune response or inappropriate cellular inflammatory response. and / or survival, an inappropriate cellular immune response or an inappropriate cellular inflammatory response, in particular, the diseases are, for example, hematological tumors, solid tumors and / or their metastases, such as leukemias and myelodysplastic syndromes, malignant lymphomas, head and neck tumors including brain tumors and brain metastases, thoracic tumors including non-small cell lung tumors and small cell lung tumors, gastrointestinal tumors, endocrine tumors, breast tumors and other gynecological tumors, urological tumors including kidney tumors, bladder tumors and prostate tumors, skin tumors and sarcomas, and / or their metastases; Alternatively, the drug is used to inhibit tumor cells, wherein the tumor cells are selected from tumor cells of blood tumors and / or solid tumors, such as breast cancer cells, liver cancer cells, lung adenocarcinoma cells, leukemia cells, leukemia cell adriamycin-resistant strains, glioblastoma cells, cervical cancer cells, colon cancer cells and / or brain microvascular endothelial cells; for example, the tumor cells are selected from at least one of human breast cancer cells MCF-7, liver cancer cells HepG2, lung adenocarcinoma cells A549, human leukemia cells HL-60, human leukemia cell adriamycin-resistant strains HL-60 / ADR, human glioblastoma cells U-87MG, human cervical cancer cells HeLa, human colon cancer cells HCT-116, human colon cancer cells Sw620, human colon cancer cells LoVo and human brain microvascular endothelial cells hCMEC / D3. Alternatively, the medicament is used to treat a hyperproliferative disorder in a mammal, or to inhibit, block, reduce, decrease, etc. cell proliferation and / or cell division and / or induce apoptosis; preferably, the hyperproliferative disorder includes but is not limited to psoriasis, keloids and other hyperplasias affecting the skin, benign prostatic hyperplasia (BpH), solid tumors such as breast cancer, respiratory cancer, lung cancer, brain cancer, reproductive cancer, digestive tract cancer, urinary tract cancer, eye cancer, liver cancer, skin cancer, head and neck cancer, thyroid cancer, parathyroid cancer and their distant metastases; Alternatively, the disorder further includes lymphoma, sarcoma and leukemia.