CN109776560A - The synthetic method of compound Paulownione C and Tomentodiplacone O - Google Patents
The synthetic method of compound Paulownione C and Tomentodiplacone O Download PDFInfo
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- CN109776560A CN109776560A CN201910237867.1A CN201910237867A CN109776560A CN 109776560 A CN109776560 A CN 109776560A CN 201910237867 A CN201910237867 A CN 201910237867A CN 109776560 A CN109776560 A CN 109776560A
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Abstract
The present invention relates to the synthetic methods of natural products Tomentodiplacone O and Paulownione C.The present invention uses 2,4,6- trihydroxy-acetophenone sulfuric monohydrate, citral, syringaldehyde and vanillic aldehyde are starting material, catalyst is made using general inorganic base, the lower methanol of toxicity makees solvent, it avoids using highly toxic pyridine, prepares two natural products Tomentodiplacone O and Paulownione C by five steps.Synthetic route of the invention is succinct, easy to operate, and green high-efficient solves the problems, such as to prepare benzopyran compounds high poison low yield, is worth with certain industrial economy.
Description
Technical field
The present invention relates to compound synthesis and Field of Drug Discovery, and in particular to natural products Tomentodiplacone O
With the synthetic method of Paulownione C.
Background technique
Tomentodiplacone O and Paulownione C are isolated from Paulownia tomentosa fruit
The two new natural products small molecules come, the two natural products molecules belong to the flavonoids with chromene ring structure
Object, therefore the general characters such as anticancer, antitumor, sterilization, anti-inflammatory with flavones are closed, and then make it have potential medical value,
And following drug development or drug are improved with certain reference significance.However, the synthetic method of both natural products
Have not yet to see open disclosure.
In the synthesis of chromene cyclics, 2,4,6- trihydroxy-acetophenone sulfuric monohydrates of document report
It is cyclized and prepares with citral, but in this operation, need using the higher dry pyridine solvent of toxicity and catalyst.And
And need to be heated to reflux in reaction process, by-product species are more in reaction process, cause chromene cyclics product
Yield and selectivity are lower.
Summary of the invention
The purpose of the present invention is to provide the synthetic methods of Tomentodiplacone O and Paulownione C, realize
To the green for the first time fully synthetic of Tomentodiplacone O and Paulownione C.
The present invention, which also resides in, solves the problems, such as to prepare benzopyran compounds high poison low yield.
The present invention makees solvent using relatively less toxic methanol, avoids using highly toxic pyridine, cheap inorganic base is such as
NaOH makees catalyst, prepares chromene substrate at room temperature, and in the synthesis process, reacts the by-product of generation
Only a kind of by-product, subsequent separation is easy, and yield significantly improves than before.
Key point mainly includes (1) synthesis compound 6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-first in the present invention
Base -3 '-pentenyl)-dihydro -1- chromene；(2) 6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-amylene
Base)-dihydro -1- chromene, 3,5- dimethoxy-4 '-hydroxy benzaldehyde, in Vanillin hydroxyl guarantor
Shield；(3) the chromene ring chalcone compound containing protecting group is synthesized；(4) the chromene ring flavanones containing protecting group is synthesized
Compound.
To achieve the above object, the technical solution that the present invention takes includes the following steps:
(1) 6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-dihydro -1- chromene is synthesized；It will
2,4,6- trihydroxy-acetophenone sulfuric monohydrates are added to single-necked flask, and addition methanol, which is stirred to solute, to be completely dissolved, and are added 97%
Citral, then NaOH is dissolved in ice-water bath after 10mL methanol is added dropwise and be added, it is warmed to room temperature after 1h, is stirred to react for 24 hours, is added dropwise
The hydrochloric acid solution quenching reaction of 3mol/L, is adjusted to pH value of solution=3 ~ 4, is extracted with ethyl acetate, and merges organic phase post-processing, column layer
Analyse isolated 6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-dihydro -1- chromene；
(2) 6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-dihydro -1- chromene, 3,5- bis-
The protection of hydroxyl in methoxyl group -4- hydroxy benzaldehyde, Vanillin；By 2,6- dihydroxy benzo pyranoid ring
Compound, syringaldehyde, vanillic aldehyde are added separately to single necked round bottom flask, and acetone is added and dissolves substrate, adds anhydrous K2CO3,
It is cooled to room temperature after reflux half an hour, simultaneously chloromethyl methyl ether MOMCl is added dropwise in agitating solution dropwise, and flow back 3h after being added dropwise to complete, and uses
Ethyl acetate extraction, merges organic phase post-processing, and column chromatography for separation obtains three groups of bottoms for having methoxy MOM protecting group
Object is denoted as compound three, compound five, compound ten respectively；
(3) synthesis of the chromene ring chalcone compound containing protecting group；
Compound three, compound five, the compound ten that step (2) is isolated are added to single necked round bottom flask, and ethyl alcohol is added and makees
For solvent, in ice-water bath N2Under atmosphere, it is vigorously stirred and is slowly added to KOH-H2O-EtOH solution, after stirring 1h after being added dropwise to complete
Ice-water bath is removed, reacts for 24 hours, is extracted with ethyl acetate under room temperature, merges organic phase post-processing, column chromatography for separation obtains two
Chromene ring chalcone compound of the group containing protecting group, is denoted as compound six, compound ten respectively；
(4) synthesis of the chromene ring flavanone compound containing protecting group；
Compound six, the compound ten that step (3) is isolated, are added to round bottom single-necked flask, and anhydrous EtOH dissolution is added, then
The drop water of NaOAc and one is added, after return stirring reacts 26h, a small amount of water is added into reaction system, ethyl acetate extraction merges
Organic phase post-processing, column chromatography for separation obtain two groups of chromene ring flavanone compounds containing protecting group, respectively being denoted as
Close object seven, compound 12；
(5) synthesis of compound Paulownione C and Tomentodiplacone O；
The compound seven of step (4) synthesis, compound 12 are dissolved in 5mL methanol, are added 3mol/L's until completely dissolved
Hydrochloric acid 1mL, is heated to reflux, and is monitored and is reacted with thin-layer chromatography, and 15min recession source cooling to room temperature of reducing phlegm and internal heat adds water 3mL, ethyl acetate
Extraction, merges organic post-processing, column chromatography for separation obtains step (5) target compound.
Citral is 1.2 times of 2,4,6- trihydroxy-acetophenone sulfuric monohydrate in step (1).
K in step (2)2CO3Amount be 6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-two
Hydrogen -1- chromene, syringaldehyde, 5 times of Vanillin integral molar quantity, chlorine
Dimethyl cellosolve MOMCl is 6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-dihydro -1- benzopyrene
It mutters, 1.2 times of 3,5- dimethoxy-4 '-hydroxy benzaldehyde, Vanillin integral molar quantity.
Scheme in order to preferably explain the present invention illustrates compound three, compound six, compound seven, chemical combination in conjunction with attached drawing
Object ten, compound ten are second-class, and are further explained with (1) ~ (13).
Specific steps can be with are as follows:
The conjunction of S1,6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-dihydro -1- chromene (2)
At.
The single port that 2,4,6- trihydroxy-acetophenone sulfuric monohydrates 1 (3.7232g, 20mmol) are added to 250mL is burnt
Bottle is added methanol (80mL) stirring and is completely dissolved to solute, is added 97% citral (3.7665g, 24mmol), then by KOH
Addition is added dropwise in ice-water bath after (3.3600g, 60mmol) is dissolved in 10mL methanol, is warmed to room temperature, is stirred to react for 24 hours, thin layer after 1h
Chromatography board monitoring reaction, is added dropwise the hydrochloric acid solution quenching reaction of 3mol/L, is adjusted to solution Ph=3 ~ 4, be extracted with ethyl acetate (3 ×
40mL), merge organic phase to be washed with water (2 × 20mL), saturated common salt washes (1 × 20mL), then by organic phase anhydrous Na2SO4It is dry
Vacuum distillation removes solvent after dry, and column chromatography for separation obtains target compound.
, 6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-dihydro -1- chromene (2)/3,
The protection of hydroxyl in 5- dimethoxy-4 '-hydroxy benzaldehyde (4)/Vanillin (9).
2,6- dihydroxy benzo pyranoid ring compound, 2/ syringaldehyde, 4/ vanillic aldehyde 9 (10mmol) is added to 50mL single port circle
Bottom flask is added acetone (25mL) and dissolves substrate, adds anhydrous K2CO3(1.6585g, 12mmol), after half an hour of flowing back
It is cooled to room temperature, simultaneously MOMCl (0.9660g, 12mmol) is added dropwise dropwise in agitating solution, and flow back 3h after being added dropwise to complete, thin layer color
Board monitoring reaction is composed, vacuum distillation removes solvent, adds a small amount of water to shift separatory funnel after the solid is completely dissolved, use ethyl acetate
Extraction is extracted with ethyl acetate (3 × 30mL), merges organic phase and is washed with water (2 × 20mL), and saturated common salt washes (1 × 20mL),
Again by organic phase anhydrous Na2SO4Vacuum distillation removes solvent after dry, and column chromatography for separation obtains target compound.
, chromene ring chalcone compound 6 and 11 containing protecting group synthesis.
The chromene ring substrate 3 for being respectively provided with hydroxyl protection base and 5/ vanillic aldehyde 10 of syringaldehyde are added to 50mL single port
5mL ethyl alcohol is added as solvent, in ice-water bath N in round-bottomed flask2Under atmosphere, it is vigorously stirred and is slowly added to KOH-H2O-EtOH
Solution stirs 1h recession and removes ice-water bath, reacts under room temperature for 24 hours after being added dropwise to complete, thin-layer chromatography board monitoring reaction, decompression is steamed
Solvent is removed in distillation, adds a small amount of water to shift separatory funnel after the solid is completely dissolved, is extracted with ethyl acetate
(3 × 30mL) merges organic phase and is washed with water (2 × 20mL), and saturated common salt washes (1 × 20mL), then by organic phase with anhydrous
Na2SO4Vacuum distillation removes solvent after dry, and column chromatography for separation obtains target compound.
, chromene ring flavanone compound 7 and 12 containing protecting group synthesis.
Chromene ring chalcone compound 6 or 11 with protecting group is added to 25mL round bottom single-necked flask, is added
Anhydrous EtOH dissolution adds the drop water of NaOAc and one and a small amount of water, second is added into reaction system after return stirring reacts 26h
Acetoacetic ester (3 × 30mL) extraction merges organic phase and is washed with water (2 × 20mL), and saturated common salt washes (1 × 20mL), then will be organic
Mutually use anhydrous Na2SO4Vacuum distillation removes solvent after dry, and column chromatography for separation obtains target compound.
, chromene ring flavanones (compound Paulownione C(8) and Tomentodiplacone O(13)) conjunction
At.
The chromene ring flavanone compound 7 or 12(0.5mmol containing protecting group that upper step is synthesized) it is dissolved in 5mL methanol
In, the hydrochloric acid 1mL of 3mol/L is added until completely dissolved, is heated to reflux, is monitored and is reacted with thin-layer chromatography, 15min recession is reduced phlegm and internal heat
Source cooling to room temperature adds water 3mL, and ethyl acetate (3 × 30mL) extraction merges organic phase and (2 × 20mL), saturated common salt is washed with water
It washes (1 × 20mL), then by organic phase anhydrous Na2SO4Vacuum distillation removes solvent after dry, and column chromatography for separation obtains mesh
Mark compound.
Detailed description of the invention
Fig. 1 is the synthetic line figure of step S1 in the embodiment of the present invention.
Fig. 2 is the synthetic line figure of step S2 in the embodiment of the present invention.
Fig. 3 is the synthetic line figure of step S3 in the embodiment of the present invention.
Fig. 4 is the synthetic line figure of step S4 in the embodiment of the present invention.
Fig. 5 is the synthetic line figure of step S5 in the embodiment of the present invention.
Fig. 6 be compound of embodiment of the present invention Paulownione C(8) whole synthetic line figure.Wherein letter difference
The chemical operation and reaction condition of representative are as follows: a) citral, NaOH, MeOH, rt; b) CH3OCH2Cl, K2CO3,
acetone, reflux; c) KOH-H2O-EtOH, N2, rt; d) CH3COONa, CH3CH2OH, reflux; e)
HCl, MeOH, 50°C, rt, 1h。
Fig. 7 be compound of embodiment of the present invention Tomentodiplacone O(13) whole synthetic line figure.Wherein word
The chemical operation and reaction condition that mother respectively represents are as follows: a) citral, NaOH, MeOH, rt; b) CH3OCH2Cl, K2CO3,
acetone, reflux; c) KOH-H2O-EtOH, N2, rt; d) CH3COONa, CH3CH2OH, reflux; e)
HCl, MeOH, 50°C, rt, 1h。
Fig. 8 be inventive embodiments compound Paulownione C(8) molecular structural formula and part carbon atoms numbered.
Fig. 9 compiles for the molecular structural formula and part carbon atom of inventive embodiments compound Tomentodiplacone O(13)
Number.
Specific embodiment
In order to which objects and advantages of the present invention are more clearly understood, the present invention is carried out with reference to embodiments further
It is described in detail.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to limit this hair
It is bright.
In following embodiment, NMR Bruker (400 and, 100 MHz) type nmr determination (CDCl3,
CD3OD, DMSO make solvent, and TMS is internal standard)；Silica gel is 200-300 mesh and GF254 (Haiyang Chemical Plant, Qingdao's production)；Reagent
It is that analysis is pure.
As shown in Figs. 1-5, the embodiment of the invention provides compound Paulownione C(8) and
Tomentodiplacone O(13) synthetic method, include the following steps:
The conjunction of S1,6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-dihydro -1- chromene (2)
At
2,4,6- trihydroxy-acetophenone sulfuric monohydrates 1 (3.7232g, 20mmol) are added to the single-necked flask of 250mL, are added
Enter CH3OH (80mL) stirring is completely dissolved to solute, is added 97% citral (3.7665g, 24mmol), then by KOH
(3.3600g, 60mmol) is dissolved in CH3Addition is added dropwise in ice-water bath to OH (10 mL) afterwards, is warmed to room temperature, is stirred to react for 24 hours after 1h,
Thin-layer chromatography board monitoring reaction, is added dropwise the hydrochloric acid solution quenching reaction of 3mol/L, is adjusted to solution Ph=3 ~ 4, is extracted with ethyl acetate
(3 × 40mL) merges organic phase and is washed with water (2 × 20mL), and saturated common salt washes (1 × 20mL), then by organic phase with anhydrous
Na2SO4Vacuum distillation removes solvent after dry, and column chromatography for separation obtains faint yellow oily compound 2(1.9932g,
6.6mmol), yield 33%.
, 6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-dihydro -1- chromene (2)/3,
The protection of hydroxyl in 5- dimethoxy-4 '-hydroxy benzaldehyde (4)/Vanillin (9).
By 2,6- dihydroxy benzo pyranoid ring compound, 2 (2.9596g, 9.8mmol)/syringaldehyde 4 (1.8218g,
10mmol)/vanillic aldehyde 9 (1.5215g, 10mmol) is added to 100mL single necked round bottom flask, and CH is added3COCH3(40mL) is the bottom of by
Object dissolution, adds anhydrous K2CO3(1.6585g, 12mmol) is cooled to room temperature, agitating solution and dropwise after half an hour of flowing back
It is added dropwise MOMCl (0.9660g, 12mmol), flow back 3h after being added dropwise to complete, and thin-layer chromatography board monitoring reaction, vacuum distillation removes
Solvent adds a small amount of water to shift separatory funnel after the solid is completely dissolved, is extracted with ethyl acetate (3 × 30mL), merges organic phase
It is washed with water (2 × 20mL), saturated common salt washes (1 × 20mL), then by organic phase anhydrous Na2SO4Vacuum distillation removes after dry
Solvent is removed, column chromatography for separation obtains faint yellow compound 3(2.577g, 7.4mmol), 76%/compound as white solid of yield 5
(1.8614g, 8.2mmol) 82%/compound as white solid of yield 10(1.6464g, 8.4mmol), yield 84%.
, chromene ring chalcone compound (6) and (11) containing protecting group synthesis.
The chromene ring substrate 3 (0.6923g, 2.0mmol) and compound 5 of hydroxyl protection base will be respectively provided with
(0.5445g, 2.4mmol)/compound 10(0.4708,2.4mmol) it is added to 50mL single necked round bottom flask, it is added
CH3CH2OH (20mL) is used as solvent, in ice-water bath N2Under atmosphere, be vigorously stirred and be slowly added to KOH (5.6281g,
100.5mmol) -H2O (5mL)-EtOH (10mL) solution stirs 1h recession and removes ice-water bath, under room temperature instead after being added dropwise to complete
Should for 24 hours, thin-layer chromatography board monitoring reaction, vacuum distillation removes solvent, and a small amount of water is added to shift liquid separation leakage after the solid is completely dissolved
Bucket, is extracted with ethyl acetate (3 × 30mL), merges organic phase and is washed with water (2 × 20mL), and saturated common salt washes (1 × 20mL), then
By organic phase anhydrous Na2SO4Vacuum distillation removes solvent after dry, and column chromatography for separation obtains yellow oily compound 6
(0.2386g, 0.43mmol), yield 22%, yellow oily compound 11(0.1991g, 0.38mmol), yield is divided into
19%。
, chromene ring flavanone compound (7) and (12) containing protecting group synthesis.
Chromene ring chalcone compound 6 (0.1128g, 0.2mmol) compound 11 of protecting group will be had
(0.1048g, 0.2mmol) is added to 25mL round bottom single-necked flask, and anhydrous CH is added3CH2OH (5mL) dissolution, adds NaOAc
A small amount of water is added into reaction system after return stirring reacts 26h in (0.3286,4mmol) and a drop water, ethyl acetate (3 ×
It 30mL) extracts, merges organic phase and be washed with water (2 × 20mL), saturated common salt washes (1 × 20mL), then by organic phase with anhydrous
Na2SO4Vacuum distillation removes solvent after dry, and column chromatography for separation obtains yellow oily compound 7(0.0577g,
0.104mmol), yield 52%, yellow oily compound 12(0.0504g, 0.096mmol), yield 48%.
, chromene ring flavanones (compound Paulownione C(8) and Tomentodiplacone O(13)) conjunction
At.
The chromene ring flavanone compound 7 (0.0376g, 0.068mmol) or 12 containing protecting group that upper step is synthesized
(0.0397g, 0.076mmol) is dissolved in CH3In OH (5mL), the hydrochloric acid (1mL) of 3mol/L is added until completely dissolved, heats back
Stream is monitored with thin-layer chromatography and is reacted, and 15min recession source cooling to room temperature of reducing phlegm and internal heat adds H2O (3mL), ethyl acetate (3 × 30mL)
Extraction merges organic phase and is washed with water (2 × 20mL), and saturated common salt washes (1 × 20mL), then by organic phase anhydrous Na2SO4It is dry
Vacuum distillation removes solvent after dry, and column chromatography for separation obtains yellow oily compound Paulownione C(8) (0.0149g,
0.032mmol), yield 47%, yellow oily compound Tomentodiplacone O(13) (0.0164g, 0.037mmol),
Yield 49%.
(8):1H NMR (CD3OD, 400MHz)δ H: 6.77 (s, 2H, H-2 ', H-6 '), 6.59 (d,J=10.0
Hz, 1H, H-1 ' '), 5.98 (s, 1H, H-8), 5.47 (d,J=10.0Hz, 1H, H-2 ' '), 5.31 (br d, J=
12.4Hz, 1H, H-2), 5.11 (t, 1H,J=7.0Hz, H-7 ' '), 3.86 (s, 6H, MeO-3 ', MeO-5 '),
3.03 (dd, 1H,J=12.8,17.0Hz, H-3 β), 2.65(br d, 1H,J=17.0Hz, H-3 α), 2.16(m, 2H,
H-6 ' '), 1.75 (m, 2H, H-5 ' '), 1.66 (s, 3H, H-9 ' '), 1.50 (s, 3H, H-10 ' '), 1.41 (s,
3H, H-4 ' ');13C NMR(CD3OD, 400MHz)δ C: 192.6 (C-4), 165.9 (C-9), 162.1 (C-7),
158.8 (C-5), 150.1 (C-3 ', C-5 '), 137.7 (C-4 '), 133.3 (C-8 ' '), 132.1 (C-1 '),
126.9 (C-2 ' '), 126.2 (C-7 ' '), 118.5 (C-1 ' '), 106.7 (C-2 ', C-6 '), 106.2 (C-6),
105.8 (C-10), 97.2 (C-8), 82.1 (C-3 ' '), 81.5 (C-2), 57.4 (MeO-3 ', MeO-5 '), 47.7
(C-3), 42. 8 (C-5 ' '), 27.5 (C-4 ' '), 24.5 (C-9 ' '), 18.5 (C-6 ' '), 15.3 (C-10 ' ')
Tomentodiplacone O (13):1H NMR(CD3OD, 400MHz)δ H: 7.06 (br s, 1H, H-2 '),
6.91 (br d, J=8.0Hz, H-6 '), 6.81 (d, 1H, J=8.0Hz, H-5 '), 6.58 (d, 1H, J=10.0Hz,
H-1 ' '), 5.97 (s, 1H, H-8), 5.46 (d, 1H, J=10.0Hz, H-2 ' '), 5.31 (br d, 1H, J=
12.5 Hz, H-2), 5.12 (t, 1H, J=7.4Hz, H-7 ' '), 3.87 (s, 3H, MeO-3 '), 3.02
(dd, 1H, J=12.5,17.0 Hz, H-3 β), 2.64 (br d, 1H, J=17.0 Hz, H-3 α), 2.16 (q,
2H, J=7.4 Hz, H-6 '), 1.64 (m, 2H, H-5 ' '), 1.57 (s, 3H, H-9 ' '), 1.56 (s, 3H,
H-10 ' '), 1.42 (s, 1H, H-4 ' ');13C NMR (CD3OD, 400 MHz)δ C: 191.8 (C-4), 165.1
(C-9), 161.3 (C-7), 157.9 (C-5), 149.0 (C-3 '), 148.0 (C-4 '), 132.4 (C-8 ' '),
132.0 (C-1 '), 126.0 (C-2 ' '), 125.4 (C-7 ' '), 120.4 (C-6), 117.6 (C-1 ' '), 116.1
(C-5 ' '), 111.1 (C-2 '), 105.9 (C-6), 105.3 (C-10), 96.2 (C-8), 81.2 (C-3 ' '),
80.4 (C-2), 56.4 (MeO-3 '), 42.0 (C-3), 41.8 (C-5 ' '), 26.6 (C-4 ' '), 25.8 (C-
9 ' '), 23.7 (C-6 ' '), 17.7 (C-10 ' ')
The above is only a preferred embodiment of the present invention, it is noted that those skilled in the art are come
It says, without departing from the principle of the present invention, can also make several improvements and retouch, these improvements and modifications also should be regarded as
Protection scope of the present invention.
Claims (3)
1. the synthetic method of compound Paulownione C and Tomentodiplacone O, it is characterised in that synthesis compound
6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-dihydro -1- chromene；It is characterized in that 6- second
Acyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-dihydro -1- chromene, 3,5- dimethoxy-4 '-hydroxyl
The protection of hydroxyl in benzaldehyde, Vanillin；It is characterized in that chromene ring of the synthesis containing protecting group
Chalcone compound；It is characterized in that chromene ring flavanone compound of the synthesis containing protecting group；
It is characterized by comprising following steps:
(1) 6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-dihydro -1- chromene is synthesized；It will
2,4,6- trihydroxy-acetophenone sulfuric monohydrates are added to single-necked flask, and addition methanol, which is stirred to solute, to be completely dissolved, and are added 97%
Citral, then KOH is dissolved in ice-water bath after 10mL methanol is added dropwise and be added, it is warmed to room temperature after 1h, is stirred to react for 24 hours, is added dropwise
The hydrochloric acid solution quenching reaction of 3mol/L, is adjusted to pH value of solution=3 ~ 4, is extracted with ethyl acetate, and merges organic phase post-processing, column layer
Analyse isolated 6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-dihydro -1- chromene；
(2) 6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-dihydro -1- chromene, 3,5- bis-
The protection of hydroxyl in methoxyl group -4- hydroxy benzaldehyde, Vanillin；By 2,6- dihydroxy benzo pyranoid ring
Compound, syringaldehyde, vanillic aldehyde are added separately to single necked round bottom flask, and acetone is added and dissolves substrate, adds anhydrous K2CO3,
It is cooled to room temperature after reflux half an hour, simultaneously chloromethyl methyl ether MOMCl is added dropwise in agitating solution dropwise, and flow back 3h after being added dropwise to complete, and uses
Ethyl acetate extraction, merges organic phase post-processing, and column chromatography for separation obtains three groups of bottoms for having methoxy (MOM) protecting group
Object is denoted as compound three, compound five, compound ten respectively；
(3) synthesis of the chromene ring chalcone compound containing protecting group；
Compound three, compound five, the compound ten that step (2) is isolated are added to single necked round bottom flask, and ethyl alcohol is added and makees
For solvent, in ice-water bath N2Under atmosphere, it is vigorously stirred and is slowly added to KOH-H2O-EtOH solution, after stirring 1h after being added dropwise to complete
Ice-water bath is removed, reacts for 24 hours, is extracted with ethyl acetate under room temperature, merges organic phase post-processing, column chromatography for separation obtains two
Chromene ring chalcone compound of the group containing protecting group, is denoted as compound six, compound ten respectively；
(4) synthesis of the chromene ring flavanone compound containing protecting group；
Compound six, the compound ten that step (3) is isolated, are added to round bottom single-necked flask, and anhydrous EtOH dissolution is added, then
The drop water of NaOAc and one is added, after return stirring reacts 26h, a small amount of water is added into reaction system, ethyl acetate extraction merges
Organic phase post-processing, column chromatography for separation obtain two groups of chromene ring flavanone compounds containing protecting group, respectively being denoted as
Close object seven, compound 12；
(5) synthesis of compound Paulownione C and Tomentodiplacone O；
The compound seven of step (4) synthesis, compound 12 are dissolved in 5mL methanol, are added 3mol/L's until completely dissolved
Hydrochloric acid 1mL, is heated to reflux, and is monitored and is reacted with thin-layer chromatography, and 15min recession source cooling to room temperature of reducing phlegm and internal heat adds water 3mL, ethyl acetate
Extraction, merges organic post-processing, column chromatography for separation obtains step (5) target compound.
2. the synthetic method of compound Paulownione C and Tomentodiplacone O according to claim 1,
Citral is 1.2 times of 2,4,6- trihydroxy-acetophenone sulfuric monohydrate in the step of being characterized in that the method (1).
3. the synthetic method of compound Paulownione C and Tomentodiplacone O according to claim 1,
K in the step of being characterized in that the method (2)2CO3Amount be 6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 ' -
Pentenyl)-dihydro -1- chromene, 3,5- dimethoxy-4 '-hydroxy benzaldehyde, Vanillin total moles
5 times of amount, chloromethyl methyl ether MOMCl is 6- acetyl group -5,7- dihydroxy -2- methyl-(4 '-methyl -3 '-pentenyl)-dihydro -
1- chromene, 3,5- dimethoxy-4 '-hydroxy benzaldehyde, 1.2 times of Vanillin integral molar quantity.
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