Stereoselective synthesis method of beta-2-deoxysugar, 2-deoxy-2-azide sugar and glucoside bond

A glucosidic bond and stereoselectivity technology, applied in chemical instruments and methods, organic chemical methods, sugar derivatives, etc. Wide range, high flexibility and universality, mild reaction conditions

Pending Publication Date: 2021-10-22
CHINA PHARM UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] For the above-mentioned deficiencies existing in the prior art, the object of the present invention is to provide a kind of method for the stereoselective synthesis of β-2-deoxysugar, 2-deoxy-2-azidosugar and glucosidic bond, to solve the problem of existing methods Problems such as poor stereoselectivity of glycosidic bonds and poor substrate applicability

Method used

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  • Stereoselective synthesis method of beta-2-deoxysugar, 2-deoxy-2-azide sugar and glucoside bond
  • Stereoselective synthesis method of beta-2-deoxysugar, 2-deoxy-2-azide sugar and glucoside bond
  • Stereoselective synthesis method of beta-2-deoxysugar, 2-deoxy-2-azide sugar and glucoside bond

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Example 1 Compound III-1

[0062] The donor Ⅰ-2 (50mg, 0.06mmol) and the corresponding acceptor (14mg, 0.05mmol) were dissolved in 2mL of dry toluene, and TMSOTf (1.4μL, 0.006mmol) was used as a catalyst to obtain compound Ⅲ-1 (41mg, 93%, β / α>20:1), white solid: 1 H NMR (500MHz, CDCl 3 )δ7.81–7.74(m,5H),7.51–7.39(m,10H),7.34–7.26(m,13H),7.18(d,J=7.8Hz,2H),5.56(d,J=5.0Hz ,1H),5.50(d,J=5.0Hz,1H),5.03(d,J=11.2Hz,1H),4.95(d,J=11.0Hz,1H),4.77–4.71(m,3H),4.59 (dd, J=7.9,2.3Hz,1H),4.42(d,J=10.9Hz,1H),4.37(d,J=7.8Hz,1H),4.31(dd,J=4.9,2.3Hz,1H) ,4.25–4.21(m,2H),4.14(dd,J=11.8,3.6Hz,1H),4.06(dd,J=11.4,3.6Hz,2H),3.68(dd,J=11.6,8.5Hz,1H ),3.59–3.54(m, 1H),3.49(dd,J=12.7,10.7Hz,2H),3.33(dd,J=20.7,11.9Hz,3H),1.72(s,3H),1.50(s, 3H), 1.44(s,3H), 1.31(s,3H), 1.31(s,3H); 13 C NMR (125MHz, CDCl 3 )δ165.8,165.8,138.7,138.6, 137.9,132.3,132.3,131.5,131.4,131.2,131.2,131.1,131.1,128.8,128.7,128.7,128.6,128.4, 128.3,128.2,128.1,127.8,127.8,127.5,109.4 ,108.6,104.3,96.4,84.4,81.2,77.2,...

Embodiment 2

[0063] Example 2 Compound III-2

[0064] The donor Ⅰ-4 (30mg, 0.038mmol) and the corresponding acceptor (8.2mg, 0.031mmol) were dissolved in 2mL of dry toluene, and TMSOTf (0.68μL, 0.0031mmol) was used as a catalyst to obtain compound Ⅲ-2 (26mg ,94%,β / α>20:1), white solid: 1 H NMR (500MHz, CDCl 3 )δ7.83(dd,J=11.6,7.5Hz,4H),7.56–7.49(m,6H), 7.41–7.33(m,8H),7.27–7.22(m,2H),5.59(d,J= 5.0Hz, 1H), 4.94(d, J=10.9Hz, 1H), 4.78(dd, J=16.4, 10.9Hz, 2H), 4.65(dd, J=7.9, 2.2Hz, 1H), 4.50(d, J=10.9Hz, 1H), 4.40(d, J=7.9Hz, 1H), 4.36(dd, J=5.0, 2.3Hz, 1H), 4.30(dd, J=14.4, 6.6Hz, 2H), 4.20( dd,J=11.9,4.0Hz,1H), 4.11–4.02(m,2H),3.78(dd,J=11.1,6.8Hz,1H),3.57–3.50(m,2H),3.42–3.33(m, 4H), 1.59(s, 3H), 1.47(s, 3H), 1.39(s, 3H), 1.37(s, 3H); 13 C NMR (125MHz, CDCl 3 )δ166.0,166.0,138.3, 138.0,132.6,132.5,132.4,131.6,131.4,131.4,131.3,131.3,129.1,129.0,128.9,128.7,128.7, 128.3,128.2,128.2,128.1,109.6,108.9,102.5,96.6 ,83.2,77.2,75.2,73.0,71.5,71.0,70.8,69.1, 67.9,66.5,64.0,39.4,38.9,26.3,2...

Embodiment 3

[0065] Example 3 Compound III-3

[0066] The donor Ⅰ-5 (30mg, 0.042mmol) and the corresponding acceptor (9.2mg, 0.035mmol) were dissolved in 2mL of dry toluene, and TMSOTf (0.68μL, 0.0031mmol) was used as a catalyst to obtain compound Ⅲ-3 (27mg ,92%, β / α=10:1), as a white solid: 1 H NMR (300MHz, CDCl 3 )δ7.79(dd, J=12.0,5.7Hz,4H),7.48(dd,J=7.5,2.9Hz,6H),7.31(dd,J=10.5,5.1Hz,8H),7.25–7.22(m ,2H),5.55(d,J=5.0Hz,1H),5.50(d,J=5.2 Hz,1H),4.83–4.77(m,1H),4.68–4.62(m,1H),4.59(dd, J=8.0,2.4Hz,1H),4.54(d,J=11.6Hz,1H),4.45(dd,J=9.5,6.0Hz,2H),4.31(dd,J=5.0,2.3Hz,1H), 4.24–4.14(m,3H),3.99(dd,J=11.9,3.3Hz,2H),3.61(dd,J=11.8,8.4Hz,2H),3.53(d,J=4.6Hz,1H),3.48 (d,J=4.4Hz,1H), 3.31–3.27(m,2H),2.43(dd,J=11.7,4.7Hz,1H),1.59(d,J=11.9Hz,1H),1.54(s, 3H), 1.43(s, 3H), 1.34(s, 3H), 1.31(s, 3H); 13 C NMR (125MHz, CDCl 3 ) Δ165.9,138.2,138.2,132.2,131.2, 131.2,131.1,131.1,128.7,128.7, 128.6,128.4,127.8, 127.7.7.4, 100.4,96.7,7.2,7.2,7.2,7.2,7.2,7.2,7.2,7.2,7.7.2,7.2,7.2,7.2,7.7.2,7.7. , 71.4, 7...

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Abstract

The invention discloses a stereoselective synthesis method of beta-2-deoxysugar, 2-deoxy-2-azide sugar or glucoside bond. According to the method, 2-diphenyl acetyl phosphino (DPPA) on a glycosyl donor is utilized, and a hydrogen-bond interaction is formed between phosphorus and oxygen and hydroxyl of a glycosyl receptor, so that a glycosidic bond with high surface selectivity is formed. According to the method, the stereoselectivity of glycosylation reaction can be efficiently controlled, and particularly, the method has huge advantages in synthesis of challenging beta-configuration 2-deoxysugar and 2-deoxy-2-azide glycoside. The method is wide in substrate application range, convenient to operate and suitable for synthesizing various saccharide molecules with biological activity. The DPPA group can be chemically and selectively removed under the mild catalytic action of Ni (OTf) 2 so that the possibility is provided for further synthesizing uronic acid or high-deoxy sugar.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a method for stereoselective synthesis of β-2-deoxysugar, 2-deoxy-2-azidosugar and glucosidic bond. Background technique [0002] β-2-deoxysugars, 2-deoxy-2-aminosugars, which widely exist in nature, or in drug molecules constitute various antibiotics (macrolides, anthracyclines, erythromycin and enediynes ) and important structural units of cardiac glycosides, C21 steroidal saponins, hyaluronic acid and other carbohydrate compounds. Because these compounds have numerous pharmacological activities, efficient synthesis of β-2-deoxysugars and 2-deoxy-2-aminosugars has great guiding significance for the development of new drugs. [0003] Since the 2-position on the sugar ring lacks an adjacent group to participate in the group, the configuration of the glycosidic bond is mainly controlled by the anomeric effect, and the thermodynamically stable α-isomer is mainly require...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H15/203C07H15/18C07H1/00C07H1/06
CPCC07H15/203C07H15/18C07H1/00C07H1/06C07B2200/07Y02P20/55
Inventor 李薇刘相来蔺叶桐
Owner CHINA PHARM UNIV
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