CN-121991156-A - Polyene rigid spiro compound and preparation method and application thereof

Abstract

The invention provides a polyene rigid spiro compound, a preparation method and application thereof. Dispersing androstenedione dimer in ethanol, adding sodium borohydride to perform regioselective reduction reaction, adding water to quench after the reaction is finished, adding dilute hydrochloric acid to perform elimination reaction, concentrating, extracting, merging organic phases, concentrating again, and purifying to obtain the polyene rigid spiro compound. The invention successfully introduces a new conjugated diene structure through the selective reduction of the specific ketocarbonyl and the specific elimination of acid promotion, and the conjugated diene structure shows remarkable proliferation inhibition activity on colorectal cancer, cervical cancer, liver cancer and breast cancer cell strains.

Inventors

• SHEN HUALIANG
• Shen Runbu
• YU GUOQI
• HU KAI
• XIE MENGYU
• XU HUITING
• LUO YANJUAN
• WU YINHAO

Assignees

• 绍兴文理学院

Dates

Publication Date

20260508

Application Date

20260106

Claims (10)

1. 1. A polyene rigid spiro compound is characterized in that the structural formula of the polyene rigid spiro compound is shown as a formula I: Formula I.
2. 2. A polyene rigid spiro compound according to claim 1, wherein the spiro central carbon atom of the polyene rigid spiro compound has S configuration.
3. 3. A process for producing a polyene rigid spiro compound according to claim 1, comprising the steps of: Dispersing androstenedione dimer in ethanol, adding sodium borohydride to perform regioselective reduction reaction, adding water to quench after the reaction is finished, adding dilute hydrochloric acid to perform elimination reaction, concentrating, extracting, merging organic phases, concentrating again, and purifying to obtain the polyene rigid spiro compound.
4. 4. The method for preparing a polyene rigid spiro compound according to claim 3, wherein the androstenedione dimer has a structural formula shown in formula II: Formula II.
5. 5. The method for producing a polyene rigid spiro compound according to claim 3, wherein the mass ratio of androstenedione dimer to sodium borohydride is 15:3-4.5; The sodium borohydride is added in batches, the adding amount of each time is 50-100 g, and the adding interval is 5-10 min.
6. 6. The method for producing a polyene rigid spiro compound according to claim 3, wherein the temperature of the regioselective reduction reaction is 0 to 5 ℃.
7. 7. The method for preparing a polyene rigid spiro compound according to claim 3, wherein the quenching reaction condition is that the temperature is 0-5 ℃, water is added in batches, the addition amount is 15mL each time, and the addition interval is 5-8 s.
8. 8. The method for producing a polyene rigid spiro compound according to claim 3, wherein the elimination reaction is carried out under the conditions of a temperature of 0 to 5℃and a dilute hydrochloric acid addition amount of 15mL each time at a time interval of 5 to 8s at a time interval of 3 to 4 pH of the reaction system.
9. 9. A process for preparing a polyene rigid spiro compound according to claim 3, wherein the purification is carried out by recrystallization or column chromatography.
10. 10. Use of the polyene rigid spiro compound as defined in claim 1 or 2 or obtained by the process according to any one of claims 3 to 9 in anticancer drugs.

Description

Polyene rigid spiro compound and preparation method and application thereof Technical Field The invention relates to the technical field of steroid compounds, in particular to a polyene rigid spiro compound, a preparation method and application thereof. Background Steroid compounds and derivatives thereof play an important role in drug development, and the unique rigid skeleton and various biological activities of the steroid compounds make the steroid compounds an important source for leading structure discovery and optimization. Chinese patent CN119409756a discloses a class of rigid spiro compounds, and preparation method and application thereof, and the structure is shown in formula (II). . The compound in the formula II has a unique spiro skeleton and a plurality of ketocarbonyl groups, and can provide valuable lead structures for subsequent structural modification and functionalization research. However, prior art deep chemical modifications of such rigid spiro compounds, especially based on the selective reduction of their specific ketocarbonyl groups to build new structures, and systematic studies of their biological activity have not been reported adequately. How to realize controllable chemical conversion on a complex spiro framework, thereby obtaining the derivative with novel structure and excellent activity, and the method is a technical problem to be solved at present. Disclosure of Invention Aiming at the defects of the prior art, the invention provides a polyene rigid spiro compound, a preparation method and application thereof, and solves the problems in the prior art. In order to achieve the above purpose, the invention is realized by the following technical scheme: according to a first aspect of the present invention there is provided a polyene rigid spiro compound having the structural formula shown in formula I: Formula I. Preferably, the spiro central carbon atom of the polyene rigid spiro compound is in S configuration. According to a second aspect of the present invention, there is provided a process for the preparation of a polyene rigid spiro compound, comprising the steps of: Dispersing androstenedione dimer in ethanol, adding sodium borohydride to perform regioselective reduction reaction, adding water to quench after the reaction is finished, adding dilute hydrochloric acid to perform elimination reaction, concentrating, extracting, merging organic phases, concentrating again, and purifying to obtain the polyene rigid spiro compound. Preferably, the androstenedione dimer has a structural formula shown in formula II: Formula II. The invention takes a compound of a formula II as a starting material, introduces a new conjugated diene structure by carrying out selective reduction and acid-promoted specific elimination on specific ketocarbonyl groups of the compound to obtain the polyene rigid spiro compound which shows remarkable proliferation inhibition activity on various humanized tumor cell strains, and the process route is as follows: 。 preferably, the mass ratio of the androstenedione dimer to the sodium borohydride is 15:3-4.5; The sodium borohydride is added in batches, the adding amount of each time is 50-100 g, and the adding interval is 5-10 min. Preferably, the temperature of the regioselective reduction reaction is 0-5 ℃. Preferably, the quenching reaction condition is that the temperature is 0-5 ℃, water is added in batches, the addition amount of each time is 15mL, and the addition interval is 5-8 s. Preferably, the condition of the elimination reaction is that dilute hydrochloric acid is added in batches at the temperature of 0-5 ℃, the addition amount of each time is 15mL, and the addition interval is 5-8 s until the pH value of the reaction system is 3-4. Preferably, the purification is performed by recrystallization or column chromatography. According to a third aspect of the present invention there is provided the use of a polyene rigid spiro compound or a polyene rigid spiro compound obtained according to the above described method of preparation in anticancer drugs. Specifically, the polyene rigid spiro compound provided by the application can be used in medicines for rectal cancer, cervical cancer, liver cancer and breast cancer through an action mechanism of inducing active oxygen (ROS) aggregation in tumor cells. Advantageous effects The invention provides a polyene rigid spiro compound, a preparation method and application thereof. The beneficial effects are as follows: (1) The polyene rigid spiro compound provided by the scheme successfully introduces a new conjugated diene structure through selective reduction and acid-promoted specific elimination of specific ketocarbonyl groups of the polyene rigid spiro compound, and has obvious proliferation inhibition activity on colorectal cancer, cervical cancer, liver cancer and breast cancer cell lines, wherein IC 50 values are 3.19+/-0.35 mu M, 10.41+/-1.9 mu M, 11.67+/-1.49 mu M and 6.92+/-0.68 mu M respectively