Unlock instant, AI-driven research and patent intelligence for your innovation.

A kind of preparation method of podophyllotoxin 4-oh derivative

A technology of podophyllotoxin and 4-OH, which is applied in the field of chemistry, can solve the problems of large shortcomings of the synthesis method, and achieve the effect of high yield and purity, and mild reaction conditions

Active Publication Date: 2018-08-10
JIANGXI NORMAL UNIV
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to provide a preparation method of podophyllotoxin 4-OH derivatives, which solves the disadvantages of compound synthesis methods in which the 4-OH of podophyllotoxin and its analogues are substituted by sugar groups, amino groups, carbons, and olefins. question

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A kind of preparation method of podophyllotoxin 4-oh derivative
  • A kind of preparation method of podophyllotoxin 4-oh derivative
  • A kind of preparation method of podophyllotoxin 4-oh derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Preparation of epipodophyllotoxin 4-O(methyl 2,3,4-tri-O-benzoyl-α-D-glucopyranose) epipodophyllotoxin glycoside,

[0025]

[0026] step 1:

[0027] Synthesis of podophyllotoxin 4-O-o-cyclopropylethynyl benzoate donor:

[0028]

[0029] Under nitrogen protection, 3.5g, 8.5mmol of podophyllotoxin and 2.4g, 12.75mmol of o-alkynylbenzoic acid were dissolved in a dry 10mL DCM solution, and then DMAP (1.58g, 12.75mmol) and DCC (3.5g, 17.02mmol) were added ), stirred at room temperature for 2 hours, when TLC showed that all the starting material disappeared, DCM (40 mL) was added to dilute the reaction mixture, the resulting solution was washed with water and saturated brine successively, evaporated and concentrated under reduced pressure to obtain a residue, which was chromatographed on silica gel (eluent system: PE:EA=3:1) to obtain (4.8g, 97%) as a white solid, [α] D 25 =-169.1(c 1,CHCl 3 ); 1 H NMR (400MHz, CDCl 3 )δ7.88(dd, J=1.2,8.0Hz,1H),7.51-7.43(m,2H),7.3...

Embodiment 2

[0035] Preparation of epipodophyllotoxin 4-O(methyl 2,3,4-tri-O-benzoyl-α-D-glucopyranose) epipodophyllotoxin glycoside,

[0036]

[0037] step 1:

[0038]

[0039] As shown in step 1 of Example 1, [α] D 25 =-50.8(c 1,CHCl 3 ); 1 H NMR (400MHz, CDCl 3 )δ7.89(dd, J=1.2,8.0Hz,1H),7.49(dd,J=1.6,8.0Hz,1H),7.45(td,J=1.6,7.2Hz,1H),7.33(td,J =1.6,8.0Hz,1H),7.00(s,1H),6.58(s,1H),6.46(d,J=3.6Hz,1H),6.32(s,2H),6.00(d,J=1.2Hz ,1H),5.96(d,J=1.6Hz,1H),4.72(d,J=5.2Hz,1H),4.45(dd,J=8.0,8.8Hz,1H),4.17(dd,J=8.8, 10.8Hz, 1H), 3.82(s, 3H), 3.76(s, 6H), 3.53(dd, J=4.8, 14.0Hz, 1H), 3.14-3.07(m, 1H), 1.40-1.36(m, 1H ),0.92-0.89(m,2H),0.81-0.73(m,2H); 13 CNMR (100MHz, CDCl 3 )δ174.0, 165.9, 152.3, 148.5, 147.1, 137.0, 134.3 (2C), 132.6, 131.7, 130.4, 130.2, 127.5, 126.9, 124.1, 109.7, 109.5, 107.8, 101.2, 979.3, 76.8.4, 7 60.4, 55.9, 43.6, 41.5, 36.6, 8.54, 8.50; HRMS (ESI) calcd for C 34 h 31 o 9 [M+H] + 583.19626found 583.19683;

[0040] Step 2:

[0041]

[0042] As shown...

Embodiment 3

[0044] Preparation of epipodophyllotoxin 4-O(methyl 2,3,4-tri-O-benzyl-α-D-glucopyranose) epipodophyllotoxin glycoside,

[0045]

[0046] step 1:

[0047] As shown in step 2 in Example 1, light yellow epipodophyllotoxin 4-O (methyl 2,3,4-tri-O-benzyl-α-D-glucopyranose) epipodophyllotoxin was obtained Glycoside 41mg, yield 95%, [α] D 25 =-19.8(c 1,CHCl 3 ); 1 H NMR (400MHz, CDCl 3 )δ7.40-7.23(m,15H),6.81(s,1H),6.52(s,1H),6.22(s,2H),6.00(d,J=1.6Hz,1H),5.95(d,J =1.6Hz,1H),5.01(d,J=10.8Hz,1H),4.90(d,J=11.2Hz,1H),4.83(d,J=12.0Hz,1H),4.82(d,J=10.4 Hz,1H),4.68(d,J=12.4Hz,1H),4.57(d,J=4.4Hz,1H),4.56(d,J=1.2Hz,1H),4.55(d,J=11.2Hz, 1H), 4.35(d, J=3.2Hz, 1H), 4.32-4.24(m, 2H), 4.01(t, J=9.2Hz, 1H), 3.79(s, 3H), 3.75(m, 1H), 3.73(s,6H),3.71(m,1H),3.61-3.51(m,1H),3.43-3.31(m,2H),3.34(s,3H),2.85-2.76(m,1H); 13 C NMR (100MHz, CDCl 3 )δ175.0, 152.5, 148.4, 146.7, 138.6, 138.2, 138.1, 137.2, 135.4, 132.5, 129.0, 128.5(2C), 128.4, 128.2, 128.1(2C), 128.0(3C), 127.9, 127.7, 107 109...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

A preparation method of a podophyllotoxin 4-OH derivative, wherein compound 2 and compound 3 are subjected to glycosylation reaction to obtain a podophyllotoxin 4-OH derivative 1; wherein, R1 is a hydroxyl protecting group commonly used in the art , the protecting group is a kind of benzyl, tert-butyldimethylsilyl, and methyl; NuH is a kind of nucleophilic hydroxyl, amino, alkyl, alkenyl or alkynyl, which can be The method is suitable for the preparation of podophyllotoxin 4‑OH derivatives, and the reaction conditions are mild, environmentally friendly, and the yield and purity of the product are high.

Description

technical field [0001] The invention relates to the field of chemistry, in particular to a preparation method of podophyllotoxin 4-OH derivatives. Background technique [0002] Lignin exists widely in the plant kingdom. As a secondary metabolite, it comes from the oxidative dimerization of phenylpropanoid. According to the traditional classification method, lignin compounds can be divided into two categories. One is the classic lignin, which is the molecule It contains β-β'(8-8')-linked lignin compounds, and the other is a new type of lignin, that is, a dimer of phenylpropanoids without β-β'-linked structures, among which the classic lignin The element can be further subdivided into aryltetralinlignin, dibenzylbutane lignan, arylnaphthalene lignan and dibenzocyclooctadiene lignan. Activity tests show that lignin compounds have very good medicinal activities, mainly including anti-tumor, anti-infection, immunosuppression, cardiovascular and cerebrovascular protection, anti-o...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07H1/00C07H15/26A61K31/7048A61P35/00
CPCY02P20/55
Inventor 孙建松万峻浩廖进喜
Owner JIANGXI NORMAL UNIV