CN116789719A - Selenoglycosyl donor, selenoside compound and preparation method of selenoglycosyl donor and selenoglycoside compound - Google Patents

Selenoglycosyl donor, selenoside compound and preparation method of selenoglycosyl donor and selenoglycoside compound Download PDF

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CN116789719A
CN116789719A CN202310731025.8A CN202310731025A CN116789719A CN 116789719 A CN116789719 A CN 116789719A CN 202310731025 A CN202310731025 A CN 202310731025A CN 116789719 A CN116789719 A CN 116789719A
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compound
reaction
donor
selenoglycosyl
selenoside
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徐春发
闫玮涛
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Fuzhou University
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Fuzhou University
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Abstract

The invention provides a selenoglycosyl donor, a selenoside compound and a preparation method thereof. The selenoglycosyl donor provided by the invention has novel structure and simple preparation method; the selenoside compound with the special beta configuration is prepared by taking the selenoglycosyl donor as a raw material and utilizing the cheap copper to catalyze the reaction, and the preparation method is simple, mild in reaction condition, high in yield and good in application prospect.

Description

Selenoglycosyl donor, selenoside compound and preparation method of selenoglycosyl donor and selenoglycoside compound
Technical Field
The invention relates to the technical field of pharmaceutical chemistry, in particular to a selenoglycosyldonor, a selenoside compound and a preparation method thereof.
Background
Selenosides are a subset of selenium-containing compounds known to have a variety of useful biological activities, particularly in their anti-metastatic, immunostimulatory and anti-tumor activities. Meanwhile, selenoside can also be used as a probe for researching carbohydrate-protein interaction. In addition, selenoside has unique reactivity as glycosyl donor, and under the conditions of light and electrochemistry, a C-Se bond easily loses electrons, so that a cation or a free radical-cation intermediate is generated, and the carbon-selenium bond is broken, so that glycosylation occurs. Currently, there are three main methods for synthesizing selenosides, as shown in FIG. 1. The first is the coupling of a glycosyl electrophile with a nucleophile for preparation (J.Carbohydr.Chem.1996, 15,183;Carbohydr.Res.1990,206,361), and the disadvantage of this type of method is that the nucleophile is not directly available, multiple steps are required for preparation, and the selenol used is toxic, has poor stability and malodor. The second is to prepare various selenosides (org. Lett.2005,7,4653) by in-situ formation of isomer selenate anions from beta-p-methylbenzoyl selenoside and reaction with various electrophiles. The third type of method is a method of reacting a glycosyl nucleophile with diselenide. Glycosylstannane is coupled with symmetrical diselenide over copper catalyst (angel. Chem. Int. Ed.2018,57,7091), however, it requires a high reaction temperature (110 ℃) and toxic alkyltin species are used in multiple steps to make the starting 1-stannyl saccharide, which is cumbersome. Therefore, the novel structure and the high-activity selenoside donor have great application value in the synthesis of selenoside.
Disclosure of Invention
For the above reasons, the present invention provides a selenoglycosyl donor, a selenoside compound, and a preparation method thereof.
In order to achieve the above purpose, the invention adopts the following technical scheme:
a selenoglycosyl donor, the structure of which is shown in formula I:
wherein the A ring is selected fromR 1 、R 2 、R 3 、R 4 Each independently selected from H, C 1-6 Alkyl, M 1 OH，M 1 OAc，M 1 OBn，M 1 OSi，M 1 Selected from 0-3 methylene groups; ar is selected from unsubstituted or substituted benzene ring, naphthalene ring, indole, quinoline and the like.
Further, the selenoglycosyl donor has a structure shown in a formula III:
wherein R is 1 、R 2 、R 3 、R 4 Each independently selected from H, C 1-6 Alkyl, M 1 OH，M 1 OAc，
M 1 OBn，M 1 OSi，M 1 Selected from 0-3 methylene groups; ar is selected from unsubstituted or substituted benzene ring, naphthalene ring, indole, quinoline and the like.
Further, the selenoglycosyl donor has a structure selected from the group consisting of:
further, the selenoglycosyl donor has a structure selected from the group consisting of:
wherein the method comprises the steps ofRepresentation->Or a mixture of the two in any proportion.
A selenoside compound having a structure according to formula II:
wherein R is 5 Selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkenyl;
ring A is selected fromR 1 、R 2 、R 3 、R 4 Each independently selected from H, C 1-6 Alkyl, M 1 OH，M 1 OAc，M 1 OBn，M 1 OSi，M 1 Selected from 0-3 methylene groups.
Further, the selenoside compound has a structure shown in a formula IV:
wherein: r5 is selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted aza aryl, oxa-heteroaryl, thia-heteroaryl, substituted or unsubstituted alkenyl.
Further, the selenoside compound has a structure selected from the group consisting of:
further, the selenoside compound has a structure selected from the group consisting of:
further, the preparation method of the selenoglycosyl donor comprises the following steps:
(1) Reacting the raw material Y1 with acetic anhydride to obtain an intermediate product Y2;
(2) Intermediate Y2 reacts with hydrobromic acid to obtain a compound Y3;
(3) Reacting raw material selenium powder with sodium borohydride to obtain a compound Z1;
(4) The compound Z1 reacts with potassium hydroxide, and then a compound Y3 is added to obtain a compound Y4;
(5) Reacting the compound Y4 with piperazine to obtain a compound Y5;
(6) Reacting a compound Y5 with thionyl chloride and sodium phenylsulfinate to obtain a selenoglycosyl donor;
wherein the structure of the raw material Y1 is thatIntermediate Y2 has the structure +.>The structure of compound Y3 is +.>The structure of the compound Z1 is +.>The structure of the compound Y4 isThe structure of compound Y5 is +.>
R 1 、R 2 、R 3 、R 4 Each independently selected from H, C 1-6 Alkyl, M 1 OH，M 1 OAc，M 1 OBn，M 1 OSi，M 1 Selected from 0-3 methylene groups.
Further, in the step (1), the reaction is performed under the action of sodium acetate; the reaction temperature is 50-150 ℃, preferably 70-110 ℃; the reaction solvent is acetic anhydride;
further, in step (2), the molar ratio of hydrogen bromide to Y2 is 10:1, preferably 5:1 to 3:1; the reaction temperature is 10-70 ℃, preferably 20-40 ℃; the reaction solvent is chloralkane, preferably dichloroethane, dichloromethane and chloroform;
further, in the step (3), the molar ratio of the selenium powder to the sodium borohydride is 0.5:5, preferably 0.5:1-0.5:3; the reaction is carried out under the action of iodine simple substance and potassium iodide; the reaction temperature is-20 to 60 ℃, preferably-10 to 30 ℃; the reaction solvent is alcohol solvent, preferably methanol, ethanol and isopropanol;
further, in the step (4), the molar ratio of the compound Z1 to the potassium hydroxide to the compound Y3 is 10:10:1-1:1, preferably 5:5:1-1:1:1, the reaction temperature before adding the Y3 is 10-70 ℃, preferably 20-40 ℃, and the reaction solvent is aromatic hydrocarbon, preferably toluene and xylene; the reaction after adding Y3 is carried out under the action of sodium carbonate and tetrabutylammonium bisulfate, and the reaction temperature after adding Y3 is 10-70 ℃, preferably 20-40 ℃; the reaction solvent is ethyl acetate;
further, in the step (5), the molar ratio of the compound Y4 to the piperazine is 5:1 to 1:5, preferably 3:1 to 1:3; the reaction temperature is 10-70 ℃, preferably 20-40 ℃; the reaction solvent is a large polar solvent, preferably DMSO, DMF, DMA, NMP;
further, in the step (6), the molar ratio of the compound Y5 to the sodium phenylsulfinate is 3:1 to 1:20, preferably 1:1 to 1:10; the reaction is carried out under the action of thionyl chloride; the reaction temperature is 10-70 ℃, preferably 20-40 ℃; the reaction solvent was acetonitrile.
Further, the preparation method of the selenoside compound comprises the following steps: reacting the selenoglycosylation donor with a glycosyl acceptor to obtain a selenoglycoside compound;
wherein the structure of the glycosyl acceptorFor (HO) 2 B-R 5 Or boron esters, potassium fluoroborate salts, etc., derived therefrom, R 5 Selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted alkenyl.
Further, the molar ratio of the glycosyl donor to the glycosyl acceptor is 5:1-1:5, preferably 2:1-1:2; the reaction is carried out under nitrogen atmosphere; the temperature of the reaction is 0-100 ℃, preferably room temperature-50 ℃; the reaction time is 12 to 48 hours, preferably 12 hours; the reaction is carried out with a copper catalyst selected from CuTc, cuCl, cuBr, cuOAc, cu 2 S,CuBr 2 ,CuF 2 Preferably CuTc, cuBr, more preferably CuTc; the solvent of the reaction is selected from THF, DMF, DMSO, CH 3 OH,1,2-DCE, toluene, preferably THF,1,2-DCE, more preferably THF.
The invention has the advantages that:
1. the configuration is single, and the problem of stereoselectivity is avoided. The traditional method often obtains an alpha, beta isomerism mixture at the step of attacking the glycosyl bromide by the selenium nucleophile, and the alpha, beta ratio is not good, so that the final product is also a mixture which is not easy to separate. The invention has no construction of a stereo center, and the obtained product is also in a single configuration.
2. The application range is wide. Most of the traditional selenoside synthesis strategies have single product structure, and phenyl sulfone selenoside and aryl boric acid can synthesize a series of aryl and heteroaryl selenosides, so that the diversity of the compounds is improved. The glycosyl donor can also participate in various reaction types, and further supplements the selenoside molecule library.
3. The post-modification of the bioactive molecule is realized. Since the aryl groups of the traditional method are often obtained from the corresponding selenoethers, but the types of selenoethers are limited, the quantity of selenoethers with bioactive structures is smaller, and thus the selenosides with bioactive structures are difficult to obtain by the traditional method. The invention is hopeful to synthesize the molecule with biological activity through phenyl sulfone selenoside.
Drawings
FIG. 1 is an overview of the synthesis of selenoside compounds.
Detailed Description
A method of preparing a selenoglycosyl donor comprising the steps of:
(1) In a solvent, reacting a glycosyl raw material with selenoether under the action of alkali to obtain an intermediate; the reaction flow formula is as follows:
(2) Under the action of alkali, the intermediate is subjected to self-coupling reaction to obtain glycosyl seleno ether; the reaction flow formula is as follows:
(3) In an organic solvent, glycosyl selenoether is converted under the action of a chloro reagent, and then reacts with phenyl sulfinic acid sodium salt to generate the needed selenoglycol donor. The reaction flow formula is as follows:
wherein, the liquid crystal display device comprises a liquid crystal display device,selected from->R 1 、R 2 、R 3 、R 4 Each independently selected from H, C 1-6 Alkyl, (CH) 2 ) n OBn、(CH 2 ) n OTMS、(CH 2 ) n OTBS、(CH 2 ) n OMe、(CH 2 ) n NHAc、(CH 2 ) n OAc, n is selected from integers from 0 to 3; LG is a leaving group selected from halogen, trichloroacetimide or p-toluenesulfonate;
further, the molar ratio of the glycosyl raw material to the selenoether used in the step (1) is 1:2; the dosage ratio of the glycosyl raw material to the solvent is l g/l mL-l g/50mL; the molar ratio of the alkali to the glycosyl raw material is 1:1-5:1.
Wherein the solvent is any one of tetrahydrofuran, toluene, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, acetone and ethyl acetate.
The alkali is any one of sodium carbonate, sodium phosphate, potassium phosphate, sodium acetate, potassium acetate and sodium alkoxide.
Further, the ratio of the alkali to the intermediate used in the step (2) is 1:1-10:1; the ratio of the intermediate to the solvent is in the range of l g/l mL-l g/50mL.
Wherein the alkali is any one of triethylamine, diisopropylamine, dimethylethanolamine, piperazine and benzenesulfonamide.
The solvent is any one of toluene, N-dimethylformamide, N-dimethylacetamide and dimethyl sulfoxide.
Further, the molar ratio of the chloro reagent to the glycosyl selenide used in the step (3) is 1:1-10:1; the molar ratio of the sodium p-toluenesulfonate to the glycosyl seleno ether is 1:1-10:1; the ratio of glycosyl selenoether to solvent is in the range of l g/l mL-l g/50mL.
Wherein the organic solvent is one or more of nitrile solvents and amide solvents. Further, the nitrile solvent is one or more of acetonitrile, propionitrile and benzonitrile; the amide solvent can be N, N-dimethylformamide or N, N-dimethylacetamide.
Further, the temperature of the reactions involved in steps (1), (2) and (3) is 50 ℃ to 100 ℃ for 1 minute to 48 hours; wherein the preferred temperature of the reaction in step (1) is 25 ℃, preferably for a time of 1-24 hours, and the preferred temperature of the reaction involved in step (2) is 25 ℃, preferably for a time of 1-24 hours.
The following examples are provided to illustrate the above features and advantages of the present invention. The method of the invention is a conventional method in the art unless specifically stated otherwise.
EXAMPLE 1 preparation of Paramygdalin
1. Selenium ether (Compound b) 1 4g,0.01 mol) (Compound b 1 Reaction step 1.2.3 Synthesis from Scheme 2 part of the literature (Org. Lett.2005,7,4653) was dissolved in toluene (23.52 ml), potassium hydroxide/methanol solution (0.566 g in 10 ml) was added, the solvent was removed by rotary evaporation after stirring for 10 minutes, and the compound b was obtained by washing with petroleum ether 2 The reaction formula is as follows:
2. 2,3,4, 6-tetra-O-acetyl-D-glucopyranose bromide (Compound a) 2 CAS 572-09-8,3.64g, 0.09 mol) was dissolved in ethyl acetate (182 ml), and Compound b was added 2 Tetrabutylammonium bisulfate (6 g,0.018 mol), sodium carbonate aqueous solution (3.85 g dissolved in 36.4 ml), stirred at normal temperature for three hours and washed with petroleum ether to obtain the objective p-methylbenzoyl selenoside a 3 (3.7g,78％)
The nuclear magnetic data are as follows: 1 HNMR(400MHz,CDCl 3 )δ7.75(d,J＝7.9Hz,2H),7.27(d,J＝6.6Hz,H),5.51(dd,J＝7.5,2.9Hz,1H),5.37–5.29(m,2H),5.17–5.19(m,1H),4.30(dd,J＝12.4,4.5Hz,1H),4.12(dd,J＝12.5,2.0Hz,1H),3.95–3.79(m,1H),2.41(s,3H),2.03(q,J＝22.2,11.7Hz,12H).
EXAMPLE 2 preparation of tetraacetyl glucose selenoether
The p-methylbenzoyl selenosides a obtained in example 1 3 (2.3 g,0.004 mol) is dissolved in N, N-dimethylformamide (49 ml), piperazine (0.44 g,0.005 mol) is added, and after stirring for 10 minutes at room temperature, petroleum ether is used for washing, thus obtaining the target product tetra-acetyl glucose selenoether a 4 (1.38g,80％)
The nuclear magnetic data are as follows: 1 H-NMR(500MHz,CDCl 3 )δ5.46(d,J＝3.4Hz,2H),5.37(dd,J＝9.7,10.3Hz,2H),5.08(dd,2H),4.93(d,J＝10.3Hz,2H),4.12(dd,2H),4.04(m,2H),2.18-1.99(4s,24H,8Ac)； 13 C-NMR(125MHz,CDCl3)δ170.2,170.1,170.0,169.5,81.2,75.5,71.5,69.4,67.1,60.8,20.9,20.6,20.6,20.5
EXAMPLE 3 preparation of 1-p-toluenesulfonylselenoetetraacetyl glucose
The tetraacetyl glucose selenoether a obtained in example 2 4 (0.261 g,0.0003 mol) was dissolved in anhydrous acetonitrile (6.4 ml), sodium p-toluenesulfonate (0.585 g, 0.003mol) was added, thionyl chloride (60 ul,0.0008 mol) was stirred at room temperature for 12 hours, then filtered, the filtrate was distilled off to remove the solvent, and the target product 1-p-toluenesulfonylselenoethanopyrrole glucose a was obtained by column chromatography (volume ratio of petroleum ether to ethyl acetate 1:1) 5 (0.157g,44％)
The nuclear magnetic data are as follows: 1 H NMR(400MHz,CDCl3)δ7.79(d,J＝8.2Hz,2H),7.32(d,J＝8.1Hz,2H),5.54(d,J＝10.5Hz,1H),5.29(t,J＝9.3Hz,1H),5.08(t,J＝9.8Hz,2H),4.17(dd,J＝12.5,4.5Hz,1H),4.02(dd,J＝12.5,2.3Hz,1H),3.81–3.74(m,1H),2.45(s,3H),2.08–1.96(m,12H).
application example 1 preparation of p-nitrophenyl tetraacetyl glucose selenoside product
1-p-toluenesulfonylselenoetetraacetyl glucose a obtained in example 3 5 (0.056 g,0.0001 mol) was dissolved in anhydrous ethyl acetate (2 ml), p-nitrobenzoic acid (0.025 g,0.00015 mol), cuprous oxide (I) (0.0028 g,0.00002 mol), 2-bipyridine (0.0031 g,0.00002 mol), sodium acetate (0.00082 g,0.0001 mol) was added, and stirred at room temperature for 12 hours to give a product having the following reaction formula, the total yield was 94%, and the α/β ratio was less than 1:20.
The nuclear magnetic data are as follows: 1 H NMR(400MHz,CDCl 3 )δ8.14–8.08(m,2H),7.73(d,J＝8.6Hz,2H),5.22(ddd,J＝9.3,6.0,2.9Hz,1H),5.08–4.96(m,3H),4.20(dd,J＝7.5,3.7Hz,2H),3.80–3.71(m,1H),2.08(s,3H),2.05(s,3H),2.01(s,3H),1.97(s,3H). 13 C NMR(101MHz,CDCl 3 )δ170.5,170.1,169.4,169.4,147.8,136.8,134.5,123.8,80.6,77.2,73.6,70.5,68.1,62.1,20.8,20.8,20.6.
application example 2 preparation of benzofuranyl tetraacetyl glucose selenoside product
1-p-toluenesulfonylselenoetetraacetyl glucose a obtained in example 3 5 (0.056 g,0.0001 mol) was dissolved in anhydrous tetrahydrofuran (2 ml), benzofuran-2-boronic acid (0.025 g,0.00015 mol), cuprous oxide (I) (0.0028 g,0.00002 mol), 2-bipyridine (0.0031 g,0.00002 mol), sodium acetate (0.00082 g,0.0001 mol) was added, and stirred at room temperature for 12 hours to give a product having the following reaction formula, the total yield was 96%, and the α/β ratio was less than 1:20.
The nuclear magnetic data are as follows: 1 H NMR(400MHz,CDCl 3 )δ7.58–7.52(m,1H),7.48(d,J＝8.2Hz,1H),7.34–7.19(m,2H),7.07(s,1H),5.19(t,J＝9.2Hz,1H),5.14–4.92(m,3H),4.15(qd,J＝12.4,3.6Hz,2H),3.69–3.65(m,1H),2.09(s,3H),1.99(d,J＝4.5Hz,6H),1.93(s,3H). 13 C NMR(101MHz,CDCl 3 ) Preparation of delta 170.6,170.2,169.5,169.4,157.6,140.5,128.5,125.2,123.2,120.9,117.4,111.4,80.5,77.2,73.8,71.1,68.0,62.0,20.9,20.7,20.6 benzothienyl tetraacetyl glucose selenosides product
1-p-toluenesulfonylselenoetetraacetyl glucose a obtained in example 3 5 (0.056 g,0.0001 mol) was dissolved in anhydrous tetrahydrofuran (2 ml), benzothiophene-2-boronic acid (0.027 g,0.00015 mol), cuprous oxide (I) (0.0028 g,0.00002 mol), 2-bipyridine (0.0031 g,0.00002 mol), sodium acetate (0.00082 g,0.0001 mol) was added, and the mixture was stirred at room temperature for 48 hours to give a productThe reaction formula is shown below, the total yield is 80%, and the alpha/beta ratio is less than 1:20.
The nuclear magnetic data are as follows: 1 H NMR(400MHz,CDCl 3 )δ7.82–7.74(m,2H),7.51(s,1H),7.39–7.30(m,2H),5.20(t,J＝9.3Hz,1H),5.05(q,J＝9.8Hz,2H),4.88(d,J＝10.0Hz,1H),4.20(d,J＝3.5Hz,2H),3.73–3.65(m,1H),2.11(s,3H),2.09–1.92(m,9H). 13 C NMR(101MHz,CDCl 3 )δ170.61,170.16,169.39,169.34,144.07,139.81,133.89,124.95,124.49,123.56,122.36,121.64,81.35,73.70,70.74,68.03,61.97,20.82,20.72,20.60,20.57.
application example 4 preparation of p-methoxyphenyl tetraacetyl glucose selenoside product
1-p-toluenesulfonylselenoetetraacetyl glucose a obtained in example 3 5 (0.056 g,0.0001 mol) was dissolved in anhydrous tetrahydrofuran (2 ml), p-methoxyphenylboronic acid (0.023 g,0.00015 mol), cuprous oxide (I) (0.0028 g,0.00002 mol), 2-bipyridine (0.0031 g,0.00002 mol), sodium acetate (0.00082 g,0.0001 mol) was added, and the mixture was stirred at room temperature for 12 hours to give a product having the following reaction formula, the total yield was 93%, and the α/β ratio was less than 1:20.
The nuclear magnetic data are as follows: 1 H NMR(400MHz,CDCl 3 )δ7.51(d,J＝8.7Hz,2H),6.85–6.78(m,2H),5.15(t,J＝9.3Hz,1H),4.94(dt,J＝22.2,9.6Hz,2H),4.75(d,J＝10.1Hz,1H),4.16(d,J＝3.6Hz,2H),3.80(s,3H),3.64(dt,J＝10.0,3.7Hz,1H),2.06(d,J＝6.3Hz,6H),1.98(d,J＝11.2Hz,6H). 13 C NMR(101MHz,CDCl 3 )δ170.59,170.21,169.41,169.30,160.38,137.94,116.17,114.59,80.45,73.89,70.68,68.11,62.04,55.26,20.83,20.74,20.60,20.57.
compared with the existing reported selenoside reagent, the phenylsulfonyl substituted selenoside has remarkable activity, and the yield of a target product is up to 91%.
a Reaction conditions 1 Compound (0.05 mmol), 2a Compound (0.06 mmol), base (0.05 mmol), copper catalyst (0.01 mmol), ligand (0.01 mmol), solvent (1 ml) were stirred at room temperature for 12 hours.
b The yield was detected by nuclear magnetic resonance spectroscopy, and trifluoromethoxybenzene was used as an internal standard.
The benzothienyl selenoside (application example 3) and the p-methoxyphenyl selenoside (application example 4) obtained by the method have better biological activity in 7901 gastric cancer cell lines, and the IC50 is respectively 10uM and 3.6uM.
The foregoing description is only of the preferred embodiments of the invention, and all changes and modifications that come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.

Claims (10)

1. A selenoglycosyl donor, characterized by: the structure of the selenoglycosyl donor is shown as a formula I:
i is a kind of
Wherein the A ring is selected from，R 1 、R 2 、R 3 、R 4 Each independently selected from H, C 1-6 Alkyl, M 1 OH，M 1 OAc，M 1 OBn，M 1 OSi，M 1 Selected from 0-3 methylene groups;
ar is selected from unsubstituted or substituted benzene ring, naphthalene ring, indole and quinoline.
2. The selenoglycosyl donor as defined in claim 1, wherein: the selenoglycosyl donor has a structure selected from the group consisting of:
。
3. the selenoglycosyl donor as defined in claim 2, wherein the selenoglycosyl donor has a structure selected from the group consisting of:
wherein the method comprises the steps ofRepresentation->，/>Or a mixture of the two in any proportion.
4. A method of preparing the selenoglycosyl donor according to any one of claims 1 to 3, wherein: the method comprises the following steps:
(1) Reacting the raw material Y1 with acetic anhydride to obtain an intermediate product Y2;
(2) Intermediate Y2 reacts with hydrobromic acid to obtain a compound Y3;
(3) Reacting raw material selenium powder with sodium borohydride to obtain a compound Z1;
(4) The compound Z1 reacts with potassium hydroxide, and then a compound Y3 is added to obtain a compound Y4;
(5) Reacting the compound Y4 with piperazine to obtain a compound Y5;
(6) Reacting a compound Y5 with thionyl chloride and sodium benzene sulfinate to obtain a selenoglycosyl donor;
wherein the structure of the raw material Y1 is thatIntermediate Y2 has the structure +.>The structure of compound Y3 is +.>The structure of the compound Z1 is +.>The structure of compound Y4 is +.>The structure of compound Y5 is +.>
R 1 、R 2 、R 3 、R 4 Each independently selected from H, C 1-6 Alkyl, M 1 OH，M 1 OAc，M 1 OBn，M 1 OSi，M 1 Selected from 0-3 methylene groups.
5. The method according to claim 4, wherein:
in the step (1), the reaction is carried out under the action of sodium acetate; the reaction temperature is 50-150 ℃; the reaction solvent is acetic anhydride;
in the step (2), the molar ratio of the hydrogen bromide to the Y2 is 10:1; the reaction temperature is 10-70 ℃; the reaction solvent is chloralkane;
in the step (3), the molar ratio of the selenium powder to the sodium borohydride is 0.5:1-0.5:3; the reaction is carried out under the action of iodine simple substance and potassium iodide; the reaction temperature is-20-60 ℃; the reaction solvent is an alcohol solvent;
in the step (4), the molar ratio of the compound Z1 to the potassium hydroxide to the compound Y3 is 10:10:1-1:1:1, the reaction temperature before adding the compound Y3 is 10-70 ℃, and the reaction solvent is aromatic hydrocarbon; the reaction after adding Y3 is carried out under the action of sodium carbonate and tetrabutylammonium bisulfate, and the reaction temperature after adding Y3 is 10-70 ℃; the reaction solvent is ethyl acetate;
in the step (5), the molar ratio of the compound Y4 to the piperazine is 5:1-1:5; the reaction temperature is 10-70 ℃; the reaction solvent is a large polar solvent;
in the step (6), the molar ratio of the compound Y5 to the sodium benzene sulfinate is 3:1-1:20; the reaction is carried out under the action of thionyl chloride; the reaction temperature is 10-70 ℃; the reaction solvent was acetonitrile.
6. A selenoside compound, characterized in that: the structure of the selenoside compound is shown as a formula II:
II (II)
Wherein R is 5 Selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted alkenyl;
ring A is selected from，R 1 、R 2 、R 3 、R 4 Each independently selected from H, C 1-6 Alkyl, M 1 OH，M 1 OAc，M 1 OBn，M 1 OSi，M 1 Selected from 0-3 methylene groups.
7. The selenoside compound of claim 6, wherein: the selenoside compound has a structure selected from the group consisting of:
。
8. the selenoside compound of claim 7, wherein: the selenoside compound has a structure selected from the group consisting of:
。
9. a process for preparing a selenoside compound as defined in any one of claims 6 to 8, characterized in that: the method comprises the following steps: reacting the selenoglycosyl donor of any one of claims 1 to 3 with a glycosyl acceptor to obtain a selenoglycoside compound;
wherein the structure of the glycosyl acceptor is thatOr a boron ester, potassium fluoroborate salt derived therefrom, R 5 Selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted alkenyl.
10. The method according to claim 9, wherein:
the molar ratio of the selenoglycosyl donor to the glycosyl acceptor is 5:1-1:5;
the reaction is carried out under nitrogen atmosphere;
the temperature of the reaction is 0-100 ℃; the reaction time is 12-48 hours;
the reaction is carried out with a copper catalyst selected from CuTc, cuCl, cuBr, cuOAc, cu 2 S, CuBr 2 , CuF 2 ;
The solvent of the reaction is selected from THF, DMF, DMSO, CH 3 OH,1,2-DCE, toluene.
CN202310731025.8A 2023-06-20 2023-06-20 Selenoglycosyl donor, selenoside compound and preparation method of selenoglycosyl donor and selenoglycoside compound Pending CN116789719A (en)

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