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CN-122010768-A - Hydroxylamine compound containing aryl allyl structure and synthesis method and application thereof

CN122010768ACN 122010768 ACN122010768 ACN 122010768ACN-122010768-A

Abstract

The invention belongs to the field of chemical synthesis, and particularly relates to a hydroxylamine compound containing an aryl allyl structure, and a synthesis method and application thereof. The hydroxylamine compound has a structure shown in formula (I) Wherein R 1 is selected from unsubstituted alkyl, cycloalkyl, naphthyl, heteroaryl or substituted or unsubstituted phenyl, R 2 is selected from substituted or unsubstituted phenyl, and the synthesis method is that nitrone and boric acid are used as raw materials, and the nitrone and boric acid are efficiently synthesized through boron migration reaction under the catalysis of R-1,1' -bi-2-naphthol. The synthesis method has the characteristics of no need of metal catalyst, simple operation, easy acquisition of organic boric acid, environment friendliness, mild reaction condition, wide substrate application range, moderate to good yield and the like, and provides a new thought for synthesizing hydroxylamine compounds. In vitro experiments show that the compounds have remarkable proliferation inhibition activity on A549, heLa and MV-411 tumor cells and have anti-tumor drug development potential.

Inventors

  • ZHENG YONGSHENG
  • LEI XIAOHUA
  • LI YIFAN
  • Luo Zuoqin
  • GAO LIMEI

Assignees

  • 中南民族大学

Dates

Publication Date
20260512
Application Date
20260113

Claims (10)

  1. 1. A hydroxylamine compound containing aryl allyl structure is characterized in that the structural formula is shown in formula (I): ; In the formula (I), R 1 is a substituted or unsubstituted phenyl or one of an unsubstituted alkyl, cycloalkyl, naphthyl and heteroaryl, and R 2 is a substituted or unsubstituted phenyl.
  2. 2. The hydroxylamine compound according to claim 1, wherein R 1 is one of phenyl, o-methylphenyl, o-methoxyphenyl, o-fluorophenyl, o-chlorophenyl, o-bromophenyl, m-methylphenyl, m-methoxyphenyl, m-fluorophenyl, m-chlorophenyl, p-methylphenyl, p-methoxyphenyl, p-tert-butylphenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-iodophenyl, p-ethynylphenyl, p-formate phenyl, p-trifluoromethylphenyl, 3, 5-dimethylphenyl, 3, 4-dimethoxyphenyl, 2, 6-dichlorophenyl, 2-naphthyl, 2-furyl, isopropyl, n-propyl, cyclohexyl, and R 2 is one of phenyl, o-methylphenyl, o-fluorophenyl, m-methylphenyl, m-methoxyphenyl, m-fluorophenyl, m-chlorophenyl, m-bromophenyl, p-methylphenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-trifluoromethylphenyl, p-formate phenyl, 3, 5-dimethoxy.
  3. 3. The hydroxylamine compound according to any one of claims 1 to 2, wherein the compound represented by formula (I) is selected from one of the structures shown below: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 。
  4. 4. A method for synthesizing a hydroxylamine compound as described in any one of claims 1 to 3, comprising the steps of: Mixing a raw material nitrone intermediate (II), a boric acid intermediate (III), a 4A molecular sieve and a catalyst R-1,1' -bi-2-naphthol in an organic solvent A under the protection of inert gas nitrogen and/or under the anhydrous and anaerobic condition, performing boron migration reaction at room temperature, and separating and purifying after the reaction is finished to obtain the hydroxylamine compound; The structural formula of the nitrone intermediate (II) is ; The structural formula of the boric acid intermediate (III) is ; The structural formula of the catalyst R-1,1' -bi-2-naphthol is ; Wherein R 1 and R 2 are as defined in any one of claims 1 to 3.
  5. 5. The method according to claim 4, wherein the organic solvent A is selected from one of 1, 2-dichloroethane, diethyl ether, 1, 4-dioxane, dichloromethane, tetrahydrofuran, methyl tert-butyl ether, toluene, acetonitrile, ethyl acetate, chloroform, chlorobenzene, and carbon tetrachloride.
  6. 6. The synthetic method according to claim 4, wherein the molar ratio of nitrone intermediate (II) to boric acid intermediate (III) is 1.0 (3.0-4.5).
  7. 7. The method of claim 4, wherein the catalyst is used in an amount of 5 to 50% of the molar amount of the nitrone intermediate.
  8. 8. Use of a hydroxylamine compound containing an arylallyl structure as described in claims 1 to 3 for the preparation of an antitumor drug.
  9. 9. Use of a hydroxylamine compound containing an arylallyl structure synthesized by the synthesis method of any one of claims 4 to 7 in the preparation of an antitumor drug.
  10. 10. The use according to claim 8 or 9, wherein the antineoplastic agent is an agent which inhibits the growth of human lung cancer cells a549, human cervical cancer cells HeLa and/or human myelogenous monocytic leukemia cells MV-411.

Description

Hydroxylamine compound containing aryl allyl structure and synthesis method and application thereof Technical Field The invention belongs to the field of chemical synthesis, and particularly relates to a hydroxylamine compound containing an aryl allyl structure, and a synthesis method and application thereof. Background Hydroxylamine is an essential backbone in modern organic synthesis, and the N-OH unit provides many unique chemical properties and serves as an attractive metal binding site in organisms. It is an increasingly common structural element in pharmaceuticals and agrochemicals, and hydroxylamine moieties are present in natural products and analogues thereof that are biologically active, such as anticancer cali Li Jimei's (CALICHEAMICIN) and emamectin (ESPERAMICIN), the potent bacterial tRNA synthase inhibitor SB-219383. As a versatile synthon, it can be further converted into numerous bioactive compounds, which is of great importance in drug development. Nitrone (Nitrone) is N-oxide of imine, in the field of organic chemistry, as a nitrogenous oxide compound, the nitrone has N-O polar bond, is an important 1, 3-dipole compound, is widely applied to cycloaddition reaction, and can react with various dipolar-philic bodies such as alkene, alkyne, allene and the like to construct a series of heterocyclic molecular frameworks. In addition, nitrone can also undergo nucleophilic addition reaction with metal organic compounds, cyano compounds and the like, and is an important electrophile. The compound containing nitrone functional groups can be used as spin capturing agents, medicines for treating diseases and medicine synthesis intermediates, and is gradually applied to synthesis of various natural products. The organic boric acid is easy to obtain and environment-friendly, and has been successful in the research fields of transition metal catalysis Suzuki-Miyaura cross coupling reaction and the like. However, efforts are still underway to drive the search for lower cost metals and even organic boric acid reaction types that do not require metal involvement. Boric acid migration reaction is an important research direction in the field of organic synthesis in recent years, and rearrangement and conversion of functional groups are realized through intramolecular or intermolecular boron atom migration, so that an efficient method is provided for constructing complex chiral molecules. Compared with the traditional transition metal catalyzed boric acid coupling reaction, the boron migration reaction does not need transition metal, and has the advantage of simple and convenient operation. Disclosure of Invention Aiming at the defects existing in the prior art, the invention aims to provide a hydroxylamine compound containing an aryl allyl structure, the structural formula of which is shown as the formula (I): ; In the formula (I), R 1 is a substituted or unsubstituted phenyl or one of an unsubstituted alkyl, cycloalkyl, naphthyl and heteroaryl, and R 2 is a substituted or unsubstituted phenyl. Further, R 1 is one of phenyl, o-methylphenyl, o-methoxyphenyl, o-fluorophenyl, o-chlorophenyl, o-bromophenyl, m-methylphenyl, m-methoxyphenyl, m-fluorophenyl, m-chlorophenyl, p-methylphenyl, p-methoxyphenyl, p-tert-butylphenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-iodophenyl, p-ethynyl phenyl, p-methylphenyl formate, p-trifluoromethylphenyl, 3, 5-dimethylphenyl, 3, 4-dimethoxyphenyl, 2, 6-dichlorophenyl, 2-naphthyl, 2-furyl, isopropyl, n-propyl, cyclohexyl, and R 2 is one of phenyl, o-methylphenyl, o-fluorophenyl, o-chlorophenyl, m-methylphenyl, m-methoxyphenyl, m-fluorophenyl, m-chlorophenyl, p-methylphenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-trifluoromethylphenyl, p-methylphenyl formate, and 3, 5-dimethoxyphenyl. Further, the compound shown in the formula (I) is selected from one of the following structures: 、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、。 the invention also provides a synthesis method of the hydroxylamine compound, which comprises the following specific steps: Mixing a raw material nitrone intermediate (II), a boric acid intermediate (III), a 4A molecular sieve and a catalyst R-1,1' -bi-2-naphthol in an organic solvent A under the protection of inert gas nitrogen and/or under the anhydrous and anaerobic condition, performing boron migration reaction at room temperature, and separating and purifying after the reaction is finished to obtain the hydroxylamine compound; The structural formula of the nitrone intermediate (II) is ; The structural formula of the boric acid intermediate (III) is; The structural formula of the catalyst R-1,1' -bi-2-naphthol is; Wherein R 1 and R 2 are as defined for formula (I). Further, the organic solvent A is selected from one of 1, 2-dichloroethane, diethyl ether, 1, 4-dioxane, dichloromethane, tetrahydrofuran, methyl tertiary butyl ether, toluene, acetonitrile, ethyl acetate, chloroform, chlorobenzene and carbon tetrachloride (preferably 1, 2-dich