CN107915699B - Synthetic method of Corallidictyalal D - Google Patents
Synthetic method of Corallidictyalal D Download PDFInfo
- Publication number
- CN107915699B CN107915699B CN201711364278.7A CN201711364278A CN107915699B CN 107915699 B CN107915699 B CN 107915699B CN 201711364278 A CN201711364278 A CN 201711364278A CN 107915699 B CN107915699 B CN 107915699B
- Authority
- CN
- China
- Prior art keywords
- iodine
- reaction
- sesquiterpene
- action
- under
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/94—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for synthesizing marine natural product Corallidictyal D, and belongs to the field of chemical synthesis. The method comprises the steps of taking sesquiterpene aldehyde 1 and 1-iodine-2, 4, 5-trialkoxy benzaldehyde 3 as starting raw materials, generating sesquiterpene hydrazone 2 through sesquiterpene aldehyde 1 and p-toluenesulfonyl hydrazide, and coupling sesquiterpene hydrazone 2 with 1-iodine-2, 4, 5-trialkoxy benzaldehyde under palladium catalysis to construct framework compounds 4 and 5 of Siphonodictyal B; the framework compound 4 is converted into a framework compound 5 under the action of iodine simple substance, and the framework compound 5 is subjected to deprotection group under the action of boron trichloride to generate Siphonodictyl B (6); siphonodictyal B (6) subsequently generates Corallidixicytal C (7) and Corallidixictyl D (8) under the action of an acid. The method has the characteristics of few reaction steps, simple and convenient operation, good product selectivity, suitability for industrial production and the like.
Description
Technical Field
The invention relates to a synthetic method of CorallidictyalalD.
Background
The marine natural product Siphonodictyl B was first isolated from the deep sea sponge Aka coralliphaga in 1981 (B S, P D, et al, Tetrahedron, 1981, 37: 979-.
less reports have been made on the synthesis of siphonodictyl B, the absolute configuration of which is not fully determined until 2015, wherein the methyl group at C-8 is in the alpha configuration. In 2015, Jonathan H George et al reported the synthesis of this compound, by coupling of sesquiterpene aldehyde and aryl bromide, and finally completed the synthesis study of SiphonodictyalB via a 10-step reaction (Markwell-Heys A W, Kuan K W, George J H. Organic letters,2015, 17 (17): 4228-4231.).
Enrique Alvarez-Manzaneda et al realized the synthesis of the natural product Corallicidic type D in 2013 through a catalytic ring-closing synthesis strategy with acid selectivity by 10 steps of reactions (Cano M J, Bouanou H, Tapia R. journal of organic chemistry, 2013, 78(18): 9196. one 9204.), but all the methods have the disadvantages of long reaction route, low yield, unsuitability for industrial production and the like.
In view of the above discussion, it is necessary to develop a chemical synthesis method of marine natural products siphonydictyal B, corallidytal C and corallidytal D, which has a simple synthetic route and low cost and is suitable for industrial production. The synthetic method of the natural product reported by the invention has the advantages of few reaction steps, simple and convenient operation, good product selectivity, suitability for industrial production and the like.
Disclosure of Invention
The invention aims to provide a method for synthesizing a marine natural product Corallidictyal D. Less reaction steps, good product selectivity and suitability for industrial production.
To achieve the above object, the present invention comprises the following steps (see the attached drawings): a) sesquiterpene aldehyde 1 reacts with p-toluenesulfonyl hydrazide to generate sesquiterpene hydrazone 2; b) catalyzing sesquiterpene hydrazone 2 and 1-iodine-2, 4, 5-trialkoxybenzaldehyde 3 to be coupled under the action of alkali to generate skeleton compounds 4 and 5; c) the skeleton compound 4 generates a skeleton compound 5 under the action of iodine through illumination; d) SiphonodictyalB (6) generates Corallidixicytal C (7) and Corallidixictyl D (8) under the action of acid.
In the synthesis step a, sesquiterpene aldehyde 1 reacts with p-toluenesulfonylhydrazide to generate sesquiterpene hydrazone 2, methanol, ethanol, tert-butyl alcohol or isopropanol are preferably selected as reaction solvents, the reaction temperature is 0 ℃ to reflux, and the reaction time is 1 ~ 12 hours.
In the synthesis step b, sesquiterpene hydrazone 2 and 1-iodine-2, 4, 5-trialkoxybenzaldehyde 3 are catalyzed to be coupled to generate skeleton compounds 4 and 5 under the action of alkali, tetrahydrofuran, toluene, acetonitrile, 1, 2-dichloroethane, 1, 4-dioxane or N, N-dimethylformamide is preferably selected as a reaction solvent, bis (triphenylphosphine) palladium dichloride, bis (acetonitrile) palladium chloride, tris (dibenzylideneacetone) dipalladium, [1,1' -bis (diphenylphosphino) ferrocene ] palladium dichloride or tetrakis (triphenylphosphine) palladium is selected as a catalyst, potassium hydroxide, sodium carbonate, cesium carbonate or potassium carbonate is selected as alkali, the reaction temperature is from room temperature to reflux, and the reaction time is 3 ~ 12 hours.
In the synthesis step C, the skeleton compound 4 is irradiated by light under the action of iodine to generate a skeleton compound 5, n-hexane, cyclohexane, diethyl ether and tetrahydrofuran are preferably selected as reaction solvents, an ultraviolet lamp, a 150 watt incandescent lamp and sunlight are preferably selected as light sources, the reaction temperature is 0 ℃ to reflux, and the reaction time is 1 ~ 12 hours.
In the synthesis step D, Siphonodictyl B (6) prepared by deprotecting a framework compound 5 under the action of boron trichloride is reacted with N-iodosuccinimide and triphenylphosphine to generate Corallidytal C (7) and Corallidytal D (8), tetrahydrofuran, dichloromethane and diethyl ether are selected as reaction solvents, the reaction temperature is 0 ℃ to room temperature, and the reaction time is 1 ~ 12 hours.
Compared with the related synthetic reports, the invention has the following characteristics:
1. The method takes sesquiterpene aldehyde 1 and 1-iodine-2, 4, 5-trialkoxy benzaldehyde 3 as starting materials, has few reaction steps, and is suitable for industrial production.
2. High total yield and good product selectivity.
Drawings
FIG. 1 is a detailed synthesis scheme of the present invention.
Detailed Description
Example 1: synthesis of sesquiterpene hydrazones (2, see attached figure)
1 g (1, 4.5 mmol) of sesquiterpene aldehyde is dissolved in 30 ml of anhydrous methanol, 1.1 g (5.4 mmol) of p-toluenesulfonyl hydrazide is added, the reaction is stirred at room temperature for 5 hours, and the reaction is detected by TLC to be finished. And concentrating to obtain 1.6 g of white solid sesquiterpene sulfonyl hydrazone, wherein the yield is 95%.
example 2: synthesis of the framework Compounds (4 and 5, see the figures)
2.0 g (2, 5.1 mmol) of sesquiterpene sulfonyl hydrazone is dissolved in 250 ml of anhydrous tetrahydrofuran, and then 490 mg (0.4 mmol) of palladium tetratriphenylphosphine and 2.65 g (19.2 mmol) of potassium carbonate are added to repeatedly discharge argon for three times, so that air is exhausted. And dissolving 1.73 g (3, 4.2 mmol) of iodo-1, 2, 4-trimethoxybenzene in 15 ml of anhydrous tetrahydrofuran, slowly dropwise adding into the reaction system, heating to 110 ℃, stirring for reaction for 10 hours, and detecting by TLC to end the reaction. 50 mL of water is added into a reaction system, ethyl acetate is used for extraction (30 mL x 3), organic phases are combined, the mixture is washed by saturated saline solution, dried by anhydrous sodium sulfate, filtered, concentrated and purified by column chromatography, and colorless oily liquid 1.77 g is obtained, and the yield is 86%.
Example 3: conversion of framework Compound 4 to framework Compound 5 (see the figure)
1.16 g (2.58 mmol) of a mixture of the skeletal compounds 4 and 5 is dissolved in 100 ml of diethyl ether, 0.1 g (0.78 mmol) of iodine is added to the system, and the mixture is stirred under the sunlight for 2 hours. 100 mL of water was added to the reaction system, extracted with ethyl acetate (20 mL × 3), the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated to give 1.15 g of a colorless oily liquid with a yield of 99%.
Example 4: synthesis of Natural products, Corallidicytal C (7) and Corallidityal D (8) (see the attached drawing).
73 mg (0.28 mmol) of triphenylphosphine and 63 mg (0.28 mmol) of N-iodosuccinimide were dissolved in 100 ml of dichloromethane and stirred at room temperature for 30 minutes. A solution of 1 g of Compound 6 (2.8 mmol) in dichloromethane was added at 0 ℃ and stirred at room temperature for 2 hours. Concentration and column chromatography purification are carried out to obtain 0.75 g of a mixture of Corallidikyal C (7) and Corallidikyal D (8), and the yield is 76%.
The invention relates to a reaction for generating sclareol hydrazone from sesquiterpene aldehyde, a palladium-catalyzed coupling reaction, an iodine-initiated free radical reaction and an acid-catalyzed olefin ring-closing reaction, and finally marine natural products, namely siphonydictyal B, corallidylytal C and corallidytal D are synthesized. The above embodiments are merely preferred examples of the present invention, and are not intended to limit the present invention in any way.
Claims (1)
1. A synthetic method of Corallidityal D is characterized by comprising the following synthetic steps:
a) Sesquiterpene aldehyde 1Reacting with p-toluenesulfonyl hydrazide to generate sesquiterpene hydrazone 2Selecting methanol, ethanol, tert-butyl alcohol or isopropanol as a reaction solvent, wherein the reaction temperature is 0 ℃ to reflux, and the reaction time is 1-12 hours;
b) Sesquiterpene hydrazone 2 under the action of base catalysisAnd 1-iodo-2, 4, 5-trialkoxybenzaldehyde 3Coupling to form the backbone compound 4Selecting tetrahydrofuran, toluene, acetonitrile, 1, 2-dichloroethane, 1, 4-dioxane or N, N-dimethylformamide as reaction solvent, bis (triphenylphosphine) palladium dichloride, bis (acetonitrile) palladium chloride, tris (dibenzylideneacetone) dipalladium and [1,1' -bis (diphenylphosphino) ferrocene]Palladium dichloride or palladium tetratriphenylphosphine is used as a catalyst, potassium hydroxide, sodium carbonate, cesium carbonate or potassium carbonate is used as alkali, the reaction temperature is from room temperature to reflux, the reaction time is 3-12 hours, and the 1-iodine-2, 4, 5-trialkoxybenzaldehyde is selected from 1-iodine-2, 4, 5-trimethoxybenzaldehyde, 1-iodine-2, 4, 5-triethoxybenzaldehyde or 1-iodine-2, 4, 5-triisopropoxybenzaldehyde;
c) Backbone compound 4Generating a skeleton compound 5 by illumination under the action of iodineselecting normal hexane, cyclohexane, diethyl ether and tetrahydrofuran as reaction solvents, using an ultraviolet lamp, a 150 watt incandescent lamp and sunlight as light sources, and carrying out reflux at the reaction temperature of 0 ℃ for 1-12 hours;
d) Siphonodictyal B (6) prepared by deprotection of backbone compound 5 under the action of boron trichlorideGenerating Corallidikytal C (7) under the action of N-iodosuccinimide and triphenylphosphineAnd Corallidictyal D (8)Tetrahydrofuran, dichloromethane and diethyl ether are selected as reaction solvents, the reaction temperature is 0 ℃ to reflux, and the reaction time is 0.5-12 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711364278.7A CN107915699B (en) | 2017-12-18 | 2017-12-18 | Synthetic method of Corallidictyalal D |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711364278.7A CN107915699B (en) | 2017-12-18 | 2017-12-18 | Synthetic method of Corallidictyalal D |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107915699A CN107915699A (en) | 2018-04-17 |
| CN107915699B true CN107915699B (en) | 2019-12-10 |
Family
ID=61893425
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711364278.7A Active CN107915699B (en) | 2017-12-18 | 2017-12-18 | Synthetic method of Corallidictyalal D |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107915699B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109096114B (en) * | 2018-10-09 | 2021-02-26 | 威海海洋生物医药产业技术研究院有限公司 | Method for synthesizing marine natural product smenodiol |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105837549B (en) * | 2016-04-18 | 2018-03-23 | 威海创惠环保科技有限公司 | A kind of ocean terpene natural products ent chromazonarol synthetic method |
-
2017
- 2017-12-18 CN CN201711364278.7A patent/CN107915699B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN107915699A (en) | 2018-04-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107266410B (en) | Synthesis method of 8-epi-puupehedione | |
| JP6190886B2 (en) | Novel ruthenium complex and process for producing methanol and diol | |
| CN107915699B (en) | Synthetic method of Corallidictyalal D | |
| CN106083803B (en) | A kind of synthetic method of marine natural products Puupehedione | |
| CN101704701B (en) | Method for reducing alkyne into cis-form olefin | |
| Dhanjee et al. | Indium-mediated allylation of aldehydes, ketones and sulfonimines with 2-(alkoxy) allyl bromides | |
| Nakamatsu et al. | The important role of solvent vapor in an organic solid state reaction | |
| CN109535120B (en) | Preparation method of 7-substituted-3, 4,4, 7-tetrahydrocyclobutane coumarin-5-ketone | |
| CN112047839A (en) | 1-iodine-3-perfluoroalkyl alkene compound and preparation method thereof | |
| CN109867614B (en) | 4, 4-dialkyl sulfide-1-phenyl-3-butylene-1-ketone derivative and synthetic method thereof | |
| Yadav et al. | Bi (OTf) 3-catalyzed allylation of epoxides: a facile synthesis of homoallylic alcohols | |
| Yadav et al. | First example of molecular iodine-catalyzed allylation and alkynylation of cyclic allylic acetates | |
| CN113214067B (en) | Preparation method of indanone compound | |
| CN107674016B (en) | Preparation method of telaprevir intermediate and intermediate thereof | |
| CN110734354B (en) | Method for preparing biaryl compound from alcohol compound | |
| CN109438402B (en) | Benzofuranone derivatives and synthesis method thereof | |
| Zhu et al. | Application of asymmetric ylide cyclopropanation in the total synthesis of halicholactone | |
| CN107954970B (en) | Method for synthesizing marine natural product Aureol | |
| CN112538010B (en) | Preparation method of artemisinin compound synthesized key intermediate | |
| CN109422654A (en) | The method of synthetic fatty amine methylated compounds | |
| Yin et al. | Acid catalysed rearrangement of a spiroketal enol ether. An easy synthesis of chrycorin | |
| CN107915610B (en) | Preparation method of cyclopentadecanone | |
| CN109867593B (en) | Gamma-hydroxy ketone derivative and synthetic method thereof | |
| CN111393385A (en) | Synthetic method of benzothiazine formaldehyde derivative | |
| JP4419761B2 (en) | A chiral phase transfer catalyst having a spiro skeleton, a process for producing the same, and an asymmetric catalytic reaction using the same. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20191113 Address after: -3-2, Huancui - Sai Avenue District of Weihai city in Shandong province 264200 eight floor Applicant after: Weihai Chuang Hui environmental protection & Technology Co., Ltd. Address before: High culture in Weihai City West Shandong province 264209 No. 2 Applicant before: Harbin University of Technology (Weihai) |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |