A photocatalytic method for glycosylation of 1,2-cis-imine esters

Abstract

This invention discloses a photocatalytic method for the glycosylation of 1,2-cis-imine esters. The photocatalyst is N-iodosuccinimide, and the promoter is visible light at a wavelength of 455 nm. Under irradiation with visible light at a wavelength of 455 nm, N-iodosuccinimide photocatalyzes the glycosylation reaction between O-glycosyl trichloroacetylimide ester donors and acceptors. This achieves the use of NIS as a photocatalyst to catalyze the α-configuration glycosyl donor to obtain a highly stereoselective glycosylation product with the α-configuration predominantly present.

Description

Technical Field

[0001] This invention belongs to the field of glycochemistry technology and relates to a photocatalytic method for the glycosylation of 1,2-cis-imine esters. Background Technology

[0002] The statements herein provide only background information in relation to this invention and do not necessarily constitute prior art.

[0003] Carbohydrates, as one of the essential substances for life activities, play a crucial role in many physiological and pathological processes, and also have important applications in medicine, materials, energy, and the environment. In particular, the synthesis of structurally well-defined carbohydrates is of significant research value when studying the bioactivity and pharmaceutical applications of carbohydrates.

[0004] Glycosylation is a core reaction in carbohydrate chemistry, and it is the most important and common chemical reaction in the elongation of sugar chains and the assembly of carbohydrate structural units. Constructing glycosidic bonds with high stereoselectivity is one of the fundamental problems in carbohydrate chemistry research and one of the greatest challenges in glycosylation.

[0005] From a synthetic perspective, the efficiency of glycosylation reactions is typically assessed based on chemical yield, regioselectivity, and α / β stereoselectivity. However, the eco-efficiency of glycosylation has been largely overlooked, especially given the continued high demand for environmentally friendly glycosylation in the era of sustainable development goals. From an energy perspective, utilizing light as an energy source to promote glycosylation reactions is beneficial. Therefore, utilizing light energy as an energy source to promote glycosylation reactions has positive implications.

[0006] O-glycosyltrichloroacetilime, as one of the most commonly used glycosyl donors, plays an important role in the chemical construction of glycosidic bonds and is widely used in the synthesis of oligosaccharides and glycoconjugates. O-glycosyltrichloroacetilime donors are highly reactive and can be activated by catalytic amounts of trimethylsilyl trifluoromethanesulfonate (TMSOTf) or boron trifluoride diethyl ether complex (BF3·Et2O), typically achieving glycosylation reactions in high yields over a relatively wide temperature range.

[0007] Numerous photocatalytic conditions have been identified that catalyze the activation of O-glycosyltrichloroacetilime esters. These include organic photoacids (phenol, naphthol, etc.), eosin Y, and ultraviolet light. However, these photocatalytic conditions often exhibit poor stereoselectivity or low yields (e.g., eosin Y, organic photoacids), or utilize relatively harsh 365nm ultraviolet light. Finding suitable photocatalytic systems can achieve cost-effective and efficient production of glycosylation products. Therefore, the search for mild photocatalytic systems with high yields, high selectivity, and especially the currently difficult-to-control 1,2-cis selectivity among O-glycosyltrichloroacetilime donors is of great significance. Summary of the Invention

[0008] To address the shortcomings of existing technologies and achieve highly stereoselective glycosidic bond construction, this invention provides a photocatalytic method for glycosylation of 1,2-cis-imine esters. Based on N-iodosuccinimide (NIS) and mild visible light at a wavelength of 455 nm, NIS is used as a photocatalyst to catalyze the α-configuration glycosyl donor to obtain a highly stereoselective glycosylation product with α-configuration as the main component.

[0009] To achieve the above objectives, the present invention is implemented through the following technical solution:

[0010] In a first aspect, the present invention provides a photocatalytic system for the glycosylation of 1,2-cis-imine esters, wherein the photocatalyst is N-iodosuccinimide and the promoter is visible light with a wavelength of 455 nm. Under irradiation with visible light with a wavelength of 455 nm, N-iodosuccinimide photocatalyzes the glycosylation reaction between O-glycosyltrichloroacetylimide ester donors and acceptors.

[0011] In a second aspect, the present invention provides a photocatalytic method for the glycosylation of 1,2-cis-imine esters, comprising the following steps:

[0012] O-glycosyltrichloroacetylimine ester donors undergo glycosylation with acceptors under the photocatalysis of N-iodosuccinimide catalyst and visible light at a wavelength of 455 nm to obtain glycosylated products.

[0013] In some embodiments, the molar ratio of the O-glycosyltrichloroacetylimide ester donor to the N-iodosuccinimide catalyst is 0.8-1.2:0.1.

[0014] In some embodiments, the O-glycosyltrichloroacetylimine ester donor is selected from one of the following compounds:

[0015]

[0016] In some embodiments, the receptor is a monohydroxy compound.

[0017] Preferably, the receptor is selected from one of the following compounds:

[0018]

[0019] In some embodiments, the molar ratio of donor to acceptor is 1:1-1.5, preferably 1:1.1-1.4, and more preferably 1:1.2.

[0020] In some embodiments, the solvent for the glycosylation reaction system is methyl tert-butyl ether.

[0021] Preferably, the glycosylation reaction is carried out in a closed anhydrous environment.

[0022] A further preferred method is to use a molecular sieve as the drying agent for the glycosylation reaction.

[0023] The beneficial effects achieved by one or more embodiments of the present invention described above are as follows:

[0024] (1) In the catalytic method of N-iodosuccinimide (NIS) of the present invention, the catalytic performance of NIS is enhanced by mild visible light with a wavelength of 455 nm, and the glycosylation product with high stereoselectivity and high yield with α-configuration as the main component can be obtained from the α-configuration glycosyl donor by solvent control.

[0025] (2) The reaction conditions use only a catalytic amount (0.1 equivalent) of NIS and environmentally friendly 455nm wavelength mild visible light, which can efficiently complete the construction of glycosidic bonds at room temperature. The system has the advantages of excellent reactivity and green economy, which proves the powerful and unique function of this method, and provides a wide range of glycosyl acceptors, achieving high glycosidic yield and stereoselectivity. Attached Figure Description

[0026] The accompanying drawings, which form part of this invention, are used to provide a further understanding of this application. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0027] Figure 1 This is the NMR spectrum of the compound obtained using compound A as the acceptor in an embodiment of the present invention;

[0028] Figure 2 The NMR spectrum of the compound obtained using compound C as the acceptor in this embodiment of the invention;

[0029] Figure 3 The NMR spectrum of the compound obtained using compound F as the acceptor in the embodiments of the present invention;

[0030] Figure 4 The NMR spectrum of the compound obtained using compound I as the acceptor in this embodiment of the invention;

[0031] Figure 5 This is the NMR spectrum of the compound obtained using compound G as the acceptor in an embodiment of the present invention. Detailed Implementation

[0032] It should be noted that the following detailed description is illustrative and intended to provide further explanation of the invention. Unless otherwise specified, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0033] In this invention, "equivalent" refers to the ratio of the amounts of substances in an interaction. For example, the meaning of "acceptor (1.2 equivalents) and donor (1.0 equivalents)" is that the molar ratio of the acceptor compound to the donor compound in the reaction is 1.2:1.

[0034] The present invention will be further described below with reference to specific embodiments.

[0035] Example 1

[0036] Glycosylation reaction between O-glycosyltrichloroacetimide donor and monohydroxy acceptor

[0037] Standard operating procedure for the reaction (1): Under an anhydrous and sealed environment in a glove box, add the dry ingredients sequentially to an 8 mL cylindrical sample vial. MS (50 mg / ml), glycosyl donor (1.0 equivalent) and acceptor (1.2 equivalent), and methyl tert-butyl ether solvent (0.1 M) were added, followed by N-iodosuccinimide (NIS) (0.1 equivalent). The mixture was stirred at room temperature under 455 nm illumination at 30-35 °C. The reaction was monitored by TLC until completion. Na₂SO₃ and NaHCO₃ were added to quench the reaction. The mixture was diluted with DCM and the precipitate was filtered through a diatomaceous earth filter. The organic layer was washed with NaHCO₃ (aq.) and NaCl (aq.), dried over Na₂SO₄, filtered, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography to obtain the corresponding glycosylated product.

[0038] In the reaction example of this glycosylation scheme, compound 1 was used as the glycosyl donor and various monohydroxy compounds (AH) were used as acceptors, resulting in high coupling yield and high α-selectivity.

[0039] The results of the glycosylation reaction are shown below:

[0040] Among them, with For example, the results of the glycosylation reaction are explained as follows: when the acceptor is compound A, the coupling yield is 70%, and the molar ratio of α-configuration glycosylation product to β-configuration glycosylation product is 11.4:1, which shows high α-selectivity.

[0041]

[0042] Example 2

[0043] Glycosylation reactions of different O-glycosyltrichloroacetylimine ester donors with 6-OH glucose (compound F) acceptors:

[0044] Standard operating procedure for the reaction (2): Under an anhydrous and sealed environment in a vacuum glove box, add the dry ingredients sequentially to an 8 mL cylindrical sample vial. MS (50 mg / ml), glycosyl donor (1.0 equivalent) and acceptor (2.0 equivalent), and methyl tert-butyl ether solvent (0.1 M) were added, followed by N-iodosuccinimide (NIS) (0.1 equivalent). The mixture was stirred at room temperature under 455 nm illumination at 30-35 °C. The reaction was monitored by TLC until completion. The reaction was quenched with Na₂SO₃ and NaHCO₃, diluted with DCM, and the precipitate was filtered through a diatomaceous earth filter. The organic layer was washed with NaHCO₃ (aq.) and NaCl (aq.), dried over Na₂SO₄, filtered, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography to obtain the corresponding glycosylated product.

[0045] In this glycosylation protocol example, compound (F) is used as a glycosyl acceptor, and different O-glycosyl trichloroacetylimine esters are used as donors.

[0046] The results of the glycosylation reaction are shown below:

[0047]

[0048] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A photocatalytic method for glycosylation of 1,2-cis-imine esters, characterized in that: Includes the following steps: O-glycosyltrichloroacetylimine ester donors undergo glycosylation with acceptors under the photocatalysis of N-iodosuccinimide catalyst and visible light at a wavelength of 455 nm to obtain glycosylated products; O-glycosyltrichloroacetylimine ester donors are selected from one of the following compounds: ； The receptor is selected from one of the following compounds: ； The solvent for the glycosylation reaction system is methyl tert-butyl ether; The glycosylation reaction is carried out in a closed anhydrous environment; Molecular sieves are used as the drying agent in the glycosylation reaction.

2. The photocatalytic glycosylation method for 1,2-cis-imine esters according to claim 1, characterized in that: The molar ratio of the O-glycosyltrichloroacetylimide ester donor to the N-iodosuccinimide catalyst is 0.8-1.2:0.

1.

3. The photocatalytic glycosylation method for 1,2-cis-imine esters according to claim 1, characterized in that: The molar ratio of donor to acceptor is 1:1-1.

5.

4. The photocatalytic glycosylation method for 1,2-cis-imine esters according to claim 3, characterized in that: The molar ratio of donor to acceptor is 1:1.1-1.

4.

5. The photocatalytic glycosylation method for 1,2-cis-imine esters according to claim 4, characterized in that: The molar ratio of donor to acceptor is 1:1.2.

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