Lignan natural product as well as intermediate and preparation method thereof

Abstract

The invention provides a lignan natural product as well as an intermediate and a preparation method thereof. The intermediate is a chiral tetrahydrofuran ring compound V or X containing three three-dimensional centers. The preparation method comprises the following steps: by taking a palladium complex generated by coordination of a palladium source and a chiral ligand as a catalyst, reacting 4-vinyl-1,3-dioxolan-2-one with a compound IV in a solvent under the action of the catalyst to obtain the chiral tetrahydrofuran ring compound V or X containing three three-dimensional centers. According to the preparation method of the lignan natural product, a chiral tetrahydrofuran ring compound V or X is adopted as a reactant for preparation, and then reduction, olefin oxidation, intramolecular cyclization and the like are conducted to finally obtain the lignan natural product with optical purity, so that compared with an existing asymmetric total synthesis method, the method is shortened in reaction steps, and has the advantages that the reaction raw materials are convenient and easy to obtain, the operation is simple, the reaction conditions are mild, and the yield, diastereoselectivity and enantioselectivity of the reaction product are high.

Description

technical field

[0001] The invention relates to the field of chemical industry, in particular to a lignan natural product and its intermediate, a preparation method of the lignan natural product, and a preparation method of an intermediate of the lignan natural product. Background technique

[0002] The natural product lignans have numerous structures due to their different substituents and different configurations of linkage modes, and widely exist in various plants. In the past few decades, 100 lignans have been isolated from various plants. A variety of lignan natural products. In addition, various biological activities of such natural products have been reported, including antitumor, antioxidant, antihypertensive, antidiabetic, anti-inflammatory and antiviral activities, etc. However, so far there are relatively few reports on asymmetric total synthesis methods for such natural products. Most of the only methods rely on chiral pools or chiral auxiliary agents to complet...

Examples

Embodiment 1

[0052] This embodiment provides an intermediate Va of lignan natural products, whose structural formula is as follows:

[0053]

[0054] The intermediate Va of the above-mentioned lignans natural products can be prepared by the following method, comprising the following steps:

[0055] Pd was added sequentially into the reaction tube 2 (dba) 3 · CHCl 3 (0.025mmol), chiral ligand (0.05mmol), ethylene carbonate (0.6mmol), compound IVa (0.5mmol) and tetrahydrofuran (5.0mL), react at 40°C for 10 hours, the reaction formula is as figure 1 shown. After the solvent was evaporated under reduced pressure, the residue was subjected to column chromatography to obtain lignan natural product intermediate Va (ie intermediate V).

[0056] This example further provides that the ligand selection of the above preparation method is adjusted, and different ligands are used to prepare lignan natural product intermediates, and the rest of the reactants and reaction conditions are the same as...

Embodiment 2

[0058] This embodiment provides an intermediate Va of lignan natural products, whose structural formula is as follows:

[0059]

[0060] The intermediate Va of the above-mentioned lignans natural products can be prepared by the following method, comprising the following steps:

[0061] Add Pd to the reaction tube sequentially 2 (dba) 3 · CHCl 3 (0.025mmol), (S)-SEGPHOS (0.05mmol), ethylene carbonate (1.2mmol), compound IVa (1mmol) and reaction solvent (10mL), react at 40°C for 10 hours, the reaction formula refers to image 3 shown. After the solvent was evaporated under reduced pressure, the residue was subjected to column chromatography to obtain lignan natural product intermediate Va (ie intermediate V).

[0062] This embodiment further provides that the solvent selection of the above-mentioned preparation method is adjusted, and different solvents are used to prepare the lignan natural product intermediate V, and the rest of the reactants and reaction conditions are...

Embodiment 3

[0064] This embodiment provides an intermediate Va of lignan natural products, whose structural formula is as follows:

[0065]

[0066] The above-mentioned a lignan natural product intermediate Va can be prepared by the following method, comprising the following steps:

[0067] Add Pd to the reaction tube sequentially 2 (dba) 3 · CHCl 3 (0.05mmol), (S)-SEGPHOS (0.1mmol), ethylene carbonate (2.4mmol), compound IVa (2mmol) and 1,4-dioxane (20.0mL), reacted for 16 hours, the reaction formula refer to Figure 5 shown. After the solvent was evaporated under reduced pressure, the residue was subjected to column chromatography to obtain lignan natural product intermediate Va (ie intermediate V).

[0068] This embodiment further provides that the reaction temperature of the above-mentioned preparation method is adjusted, and the lignan natural product intermediate V is prepared by using different reaction temperatures. Image 6 It can be seen from the reaction results that t...

technical field

[0001] The invention relates to the field of chemical industry, in particular to a lignan natural product and its intermediate, a preparation method of the lignan natural product, and a preparation method of an intermediate of the lignan natural product. Background technique

[0002] The natural product lignans have numerous structures due to their different substituents and different configurations of linkage modes, and widely exist in various plants. In the past few decades, 100 lignans have been isolated from various plants. A variety of lignan natural products. In addition, various biological activities of such natural products have been reported, including antitumor, antioxidant, antihypertensive, antidiabetic, anti-inflammatory and antiviral activities, etc. However, so far there are relatively few reports on asymmetric total synthesis methods for such natural products. Most of the only methods rely on chiral pools or chiral auxiliary agents to complet...

Examples

Embodiment 1

[0052] This embodiment provides an intermediate Va of lignan natural products, whose structural formula is as follows:

[0053]

[0054] The intermediate Va of the above-mentioned lignans natural products can be prepared by the following method, comprising the following steps:

[0055] Pd was added sequentially into the reaction tube 2 (dba) 3 · CHCl 3 (0.025mmol), chiral ligand (0.05mmol), ethylene carbonate (0.6mmol), compound IVa (0.5mmol) and tetrahydrofuran (5.0mL), react at 40°C for 10 hours, the reaction formula is as figure 1 shown. After the solvent was evaporated under reduced pressure, the residue was subjected to column chromatography to obtain lignan natural product intermediate Va (ie intermediate V).

[0056] This example further provides that the ligand selection of the above preparation method is adjusted, and different ligands are used to prepare lignan natural product intermediates, and the rest of the reactants and reaction conditions are the same as...

Embodiment 2

[0058] This embodiment provides an intermediate Va of lignan natural products, whose structural formula is as follows:

[0059]

[0060] The intermediate Va of the above-mentioned lignans natural products can be prepared by the following method, comprising the following steps:

[0061] Add Pd to the reaction tube sequentially 2 (dba) 3 · CHCl 3 (0.025mmol), (S)-SEGPHOS (0.05mmol), ethylene carbonate (1.2mmol), compound IVa (1mmol) and reaction solvent (10mL), react at 40°C for 10 hours, the reaction formula refers to image 3 shown. After the solvent was evaporated under reduced pressure, the residue was subjected to column chromatography to obtain lignan natural product intermediate Va (ie intermediate V).

[0062] This embodiment further provides that the solvent selection of the above-mentioned preparation method is adjusted, and different solvents are used to prepare the lignan natural product intermediate V, and the rest of the reactants and reaction conditions are...

Embodiment 3

[0064] This embodiment provides an intermediate Va of lignan natural products, whose structural formula is as follows:

[0065]

[0066] The above-mentioned a lignan natural product intermediate Va can be prepared by the following method, comprising the following steps:

[0067] Add Pd to the reaction tube sequentially 2 (dba) 3 · CHCl 3 (0.05mmol), (S)-SEGPHOS (0.1mmol), ethylene carbonate (2.4mmol), compound IVa (2mmol) and 1,4-dioxane (20.0mL), reacted for 16 hours, the reaction formula refer to Figure 5 shown. After the solvent was evaporated under reduced pressure, the residue was subjected to column chromatography to obtain lignan natural product intermediate Va (ie intermediate V).

[0068] This embodiment further provides that the reaction temperature of the above-mentioned preparation method is adjusted, and the lignan natural product intermediate V is prepared by using different reaction temperatures. Image 6 It can be seen from the reaction results that t...

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