KR101747694B1 - Synthetic method of 1,3-substituted diphenylpropenes - Google Patents

Synthetic method of 1,3-substituted diphenylpropenes Download PDF

Info

Publication number
KR101747694B1
KR101747694B1 KR1020160010208A KR20160010208A KR101747694B1 KR 101747694 B1 KR101747694 B1 KR 101747694B1 KR 1020160010208 A KR1020160010208 A KR 1020160010208A KR 20160010208 A KR20160010208 A KR 20160010208A KR 101747694 B1 KR101747694 B1 KR 101747694B1
Authority
KR
South Korea
Prior art keywords
compound
compounds
substituted
formula
nmr
Prior art date
Application number
KR1020160010208A
Other languages
Korean (ko)
Inventor
전종갑
정종운
Original Assignee
한림대학교 산학협력단
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 한림대학교 산학협력단 filed Critical 한림대학교 산학협력단
Priority to KR1020160010208A priority Critical patent/KR101747694B1/en
Application granted granted Critical
Publication of KR101747694B1 publication Critical patent/KR101747694B1/en

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
    • C07C37/11—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms
    • C07C37/20—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by reactions increasing the number of carbon atoms using aldehydes or ketones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
    • C07C37/48—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by exchange of hydrocarbon groups, which may be substituted, from the same of other compounds, e.g. transalkylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
    • C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
    • C07C37/88—Use of additives, e.g. for stabilisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
    • C07C39/205—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
    • C07C39/205—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings
    • C07C39/21—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic, containing only six-membered aromatic rings as cyclic parts with unsaturation outside the rings with at least one hydroxy group on a non-condensed ring

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Problem: To provide a method for efficiently synthesizing a natural 1,3-substituted diphenylpropene compound having biological activity
Solution: The present inventors first invented an effective method for synthesizing 1,3-substituted diphenylpropene compounds 5-8 using Friedel-Craft alkylation as a main step.

Description

Synthetic method of 1,3-substituted diphenylpropenes < RTI ID = 0.0 >

The present invention relates to a method for synthesizing 1,3-substituted diphenylpropene compounds, and more particularly, to an effective method for synthesizing 1,3-substituted diphenylpropene compounds 5-8 by using Friedel-Crafts alkylation as a main step .

Flavonoids are low-molecular-weight phytochemicals obtained in nature and have many biological properties that are useful for human health [1]. 1,3-Diarylpropenes (cinnamylphenols) are biologically active compounds that have chemical units such as C 6 + C 3 + C 6 and belong to flavonoids. These small compounds are known to exhibit pharmacological properties including anticancer [2], antioxidant [3], antiinflammatory [4], antiplatelet [5] and anti-malarial function. These compounds can also function as intermediates important in the synthesis of natural compounds and in the evolution of biologically active compounds [7]. In recent years, there has been increasing interest worldwide in the synthesis of this particular structure [8].

The formula of the 1,3-substituted diphenylpropene is shown in FIG. Isomucronustyrene (Compound 1) was isolated from the core of Dalbergia odorifera (Leguminosae) [4], dalparvinene (Compound 2) was isolated from the core of Dalbergia odorifera Flora ( Dalbergia parviflora ) [9], and dalberatins AD (compounds 7, 8, 3 and 4, respectively) were also isolated from Dalbergia . Mucronustyrene (Compound 5) is known as Machaerium mucronulatum , (Fabaceae), whereas compound 6 is a synthetic E -isomer of mucronulastric styrene [11].

Singh, M .; Kaur, M .; Silakari. O. Eur. J. Med. Chem. 2014, 84, 206-239. (a) Moriyasu. M .; Nakatani, N .; Ichimaru, M .; Nishiyama, Y .; Kato, A .; Mathenge, S. G .; Juma, F. D .; Mutiso, P. B. C. J. Nat. Med. 2011, 65, 313-321. (b) Shen, C. -C .; Wang, S.-T .; Tsai, S.-Y .; Yang, H. -C .; Shieh, B. -J .; Chen, C. -C. J. Nat. Prod. 2005, 68, 791-793. (c) Cheenpracha, S .; Karalai, C .; Ponglimanont, C .; Kanjana-Opas, A. J. Nat. Prod. 2009, 72, 1395-1398. Cheenpracha, S .; Ritthiwigrom, T .; Karalai, C .; Laphookhieo, S. Phyt. Lett. 2012, 5, 708-712. Goda, Y .; Katayama, M .; Ichikawa, K .; Shibuya, M .; Kiuchi, F .; Sankawa, U. Chem. Pharm. Bull. 1985, 33, 5606-5609. Goda, Y .; Kiuchi, F .; Shibuya, M .; Sankawa, U. Chem. Pharm. Bull. 1992,40, 2452-2457. Oketch-Rabah, H. A .; Dossaji, S. F .; Christensen, S. B .; Frydenvang, K .; Lemmich, E .; Cornett, C .; Olsen, C. E .; Chen, M .; Kharazm, A .; Theander, T. J. Nat. Prod. 1997, 60, 1017-1022. (a) Water, C. -R .; Shen, Y. -C .; Kuo, P. -C .; Leu, Y.-L .; Damu, A. G .; Wang, Y. -H .; Wu. T. -S. Bioorg. Med. Chem. Lett. 2006, 16, 6155-6160. (b) Anderson, J. C .; McCarthy, R. A .; Paulin, S.; Taylor, P. W. Bioorg. Med. Chem. Lett. 2011, 21, 6996-7000. (c) Strych, S .; Trauner, D. Angew. Chem. Int. Ed. 2013, 52, 9509-9512. (a) Takashi, M .; Taketo, K .; Taichi, A .; Tomoko, K .; Tsutomu, F .; Masami, S. Eur. J. Org. Chem. 2013, 8, 1501-1505. (b) Zhao, Y .; Sun, L .; Zeng, T .; Wang, J .; Peng, Y .; Song, G. Org. Biomol. Chem. 2014, 12, 3493-3498. Songsiang, U .; Wanich, S .; Pitchuanchom, S .; Netsopa, S .; Uanporn, K .; Yenjai, C. Fitoterapia 2009, 80, 427-431. Ito, C .; Itoigawa, M .; Kanematsu, T .; Ruangrungsi, N .; Higashihara, H .; Tokuda, H .; Nishino, H .; Furukawa, H. J. Nat. Prod. 2003, 66, 1574-1577. Kurosawa, K .; Ollis, W .; Sutherland, I .; Gottlieb, O .; De Oliveira, A. Phyt. 1978, 17, 1389-1394. (a) Kim, S. -J .; Kim, C. G .; Yun, S. -R .; Kim, J. -K .; Jun, J. -G. Bioorg. Med. Chem. Lett. 2014, 24, 181-185. (b) Seo, Y. H .; Kim, J. -K .; Jun, J. -G. Bioorg. Med. Chem. Lett., 2014, 24, 5727-5730. (c) Kim, C. G .; Jun, J. -G. Bull. Korean Chem. S ° C. 2015, 36, 2278-2283.

Disclosure of the Invention The object of the present invention is to provide a method for efficiently synthesizing a natural 1,3-substituted diphenylpropene compound having biological activity.

As one of the ongoing interests in the synthesis of biologically active compounds and their analogs, the present inventors have invented a method for efficiently synthesizing natural compound 1,3-substituted diphenylpropene compounds 5, 7, 8 and its synthetic compound 6 Respectively.

The synthesis of 1,3-substituted diphenylpropene compounds 5 to 8 is shown in FIG. Synthesis of 1,3-substituted diphenylpropenes 5-8 began with protecting the 2-hydroxybenzaldehyde (Compound 29), 10, 11 with benzyl bromide, resulting in the aldehyde compound protected with a benzyl group 30 to 32 were obtained. These compounds were subjected to Grignard reaction with vinyl magnesium bromide to obtain allyl alcohol compounds 33 to 35. 2,3-Dimethoxyphenol (Compound 36) was protected with a benzyl group.

Next, Cu in anhydrous CH 2 Cl 2 Compound 37 with Compound 19 and compound 33 ~ 35 (OTf) 2 / 4Å MS using a Friedel-Crafts alkylation by benzyl protective groups is 1,3-di-substituted Phenylpropene compounds 38-41 were obtained as major products. The present inventors have attempted to react by introducing bulky benzyl-, TBS-, and trityl protecting groups in order to allow Friedel-Craft alkylation to take place at the desired position, but the reaction with an element protected with TBS- and an element protected with trityl- Yield was significantly lower than that of the Friedel - Craft alkylation protected with a benzyl group. Only when Friedel-Craft alkylation was carried out by introducing a benzyl group, desired results were obtained in a high yield in a position-selective manner. Finally, 1.0 at < RTI ID = 0.0 > M BCl 3 solution to effect benzyl group deprotection of the compounds 39 to 41 to obtain compounds 5 to 8 in a high yield. All target compounds 5-8 were identified by NMR ( 1 H- and 13 C-) and MS data.

In conclusion, the present inventors first invented an effective method for synthesizing 1,3-substituted diphenylpropene compounds 5-8 with Friedel-Craft alkylation as a main step.

According to the method of the present invention, a natural 1,3-substituted diphenylpropene compound can be synthesized with a high yield by a simple process.

1 is a chemical structural formula of a 1,3-substituted diphenylpropene compound.
2 is a chemical reaction formula showing the method for synthesizing the 1,3-substituted diphenylpropene compound of the present invention. Reagents and reaction conditions: a) Benzyl bromide, K 2 CO 3 , DMF, 40 ° C, 4h. b) 1.0 M vinyl magnesium bromide solution, dry THF, 0 C to room temperature, 2 h. c) benzyl bromide, K 2 CO 3 , acetone, 40 ° C, 6h. d) Cu (OTf) 2 , 4 Å MS, anhydrous CH 2 Cl 2 , room temperature, 3 h. e) 1.0 M BCl 3 solution, anhydrous CH 2 Cl 2 , -40 ° C, 1 h.

Hereinafter, the configuration of the present invention will be described in more detail with reference to specific embodiments. However, it is apparent to those skilled in the art that the scope of the present invention is not limited to the description of the embodiments.

All chemicals were used without purification as purchased unless otherwise noted. All the solvents used in the reaction were distilled under a nitrogen gas with an appropriate dehydrating agent. All solvents used in the chromatography were purchased and immediately used without further purification. Thin-film chromatography (TLC) was performed on plates coated with silica gel on a DC-Plasticfolien 60, F 254 (Merck, 0.2 mm thick) plastic plate and observed with UV (254 nm) or with p- anisaldehyde And stained with phosphomolybdic acid (PMA). Chromatographic purification was performed using Kieselgel 60 (60-120 mesh, Merck). NMR spectra were recorded at 300 MHz FT-NMR on a Varian Mercury and 75 MHz for 13 C, chemical shifts (δ) were expressed in parts per million (ppm) relative to TMS, coupling constants ( J ) in Hz Respectively. CDCl 3 was used as solvent and internal standard. Mass spectra were recorded using a JMS-700 (JEOL) spectrometer. Melting points were measured on a MEL-TEMP II device and were not calibrated. The peak cleaved pattern is abbreviated as follows: s (singlet), br s (broad singlet), d (doublet), dd (doublet of doublets), t (triplet) and m (multiplet). CDCl 3 / CD 3 OD / CD 3 COCD 3 was used as a solvent and an internal standard. Mass spectra were recorded using an Agilent-5977E spectrometer. Melting points were measured on the MEL-TEMP II apparatus and not calibrated.

3- Hydroxy -2- Methoxybenzaldehyde  {3- Hydroxy -2- methoxybenzaldehyde } (Compound 10):

To a stirred solution of 2,3-dihydroxybenzaldehyde (1.00 g, 7.24 mmol) in anhydrous DMF (20 mL) was added K 2 CO 3 (1.00 g, 7.24 mmol) and the mixture was stirred at room temperature for 30 minutes. CH 3 I (0.54 mL, 8.68 mmol) was then slowly added to the mixture and stirred for 8 hours. After completion of the reaction, it was neutralized by addition of 1N HCl and extracted with ether (3 x 30 mL). The combined organic solvent layers were washed with water (3 x 40 mL), brine (3 x 40 mL), dried over anhydrous Na 2 SO 4 and concentrated in vacuo. The crude compound was purified by column chromatography (EtOAc: Hexane = 1: 4) to give a white solid compound 10 (0.80 g, 73%). Rf = 0.20 (EtOAc: hexane = 1: 4); Melting point 113 ~ 115 ℃; 1 H NMR (300 MHz, CDCl 3) δ 10.3 (1H, s), 7.38 (1H, dd, J = 7.8, 2.1 Hz), 7.25 (1H, dd, J = 7.8, 2.1 Hz), 7.16 (1H, t, J = 7.8 Hz), 5.82 (1H, s), 3.99 (3H, s); 13 C NMR (75 MHz, CDCl 3) δ 189.5, 149.3, 148.9, 128.9, 125.0, 121.7, 121.6, 64.0

Benzyl group Protective  Typical procedure:

K 2 CO 3 (1.5 mmol, 1.5 eq.) Was added to the stirred solution of hydroxybenzaldehyde (1.0 mmol, 1.0 eq.) In anhydrous DMF (7 mL) and the mixture was stirred at room temperature for 20 minutes. Benzyl bromide (1.2 mmol, 1.2 eq.) Was added dropwise to the mixture and stirred at 40 째 C for four hours. After completion of the reaction, it was cooled to room temperature, neutralized with 1N HCl and extracted with ether (3 x 25 mL). The combined organic solvent layers were washed with water (3 x 30 mL), brine (3 x 30 mL), dried over anhydrous Na 2 SO 4 and concentrated in vacuo. The crude compound was purified by column chromatography (EtOAc: Hexane = 1: 5-1: 4) to obtain the compound.

2- (benzyloxy) benzaldehyde {2- (Benzyloxy) benzaldehyde}(Compound 30): Yield: 97%; Colorless liquid; Rf = 0.55 (EtOAc: hexane = 1: 5); 1 H NMR (300 MHz, CDCl 3) δ 10.5 (1H, s), 7.84 (1H, dd, J = 7.8, 1.8 Hz), 7.51 (1H, td, J = 7.8, 1.8 Hz), 7.44-7.33 ( 5H, m), 7.04 (1H, d, J = 8.4 Hz), 7.02 (1H, t, J = 8.4 Hz), 5.18 (2H, s); 13 C NMR (75 MHz, CDCl 3 )? 189.4, 161.0, 136.0, 135.7, 128.6, 128.4, 128.2, 127.2, 125.3, 121.0, 113.1, 70.6

4- (benzyloxy) -2-methoxy-benzaldehyde {3- (Benzyloxy) -2-methoxybenzaldehyde } ( Compound 31): Yield: 98%; White solid; Rf = 0.56 (EtOAc: hexane = 1: 5); mp 70-71 [deg.] C; 1 H NMR (300 MHz, CDCl 3) δ 10.4 (1H, s), 7.45-7.33 (6H, m), 7.19 (1H, dd, J = 8.1, 1.8 Hz), 7.08 (1H, t, J = 7.8 Hz), 5.14 (2 H, s), 4.02 (3 H, s); 13 C NMR (75 MHz, CDCl 3) δ 190.2, 153.3, 152.2, 136.5, 130.2, 128.9, 128.4, 127.5, 124.3, 120.3, 120.0, 71.4, 62.6.

2- (benzyloxy) -5-methoxy-benzaldehyde {2- (Benzyloxy) -5-methoxybenzaldehyde } ( Compound 32): Yield: 97%; White solid; Rf = 0.51 (EtOAc: hexane = 1: 5); mp 51-52 [deg.] C; 1 H NMR (300 MHz, CDCl 3) δ 10.47 (1H, s), 7.40-7.30 (6H, m), 7.07 (1H, dd, J = 9.0, 3.0 Hz), 6.96 (1H, d, J = 9.0 Hz), 5.10 (2H, s), 3.75 (3H, s); 13 C NMR (75 MHz, CDCl 3) δ 189.1, 155.5, 153.6, 136.0, 128.5, 128.0, 127.1, 125.2, 123.2, 114.9, 110.1, 71.1, 55.6

1- (benzyloxy) -2,3-dimethoxy benzene, {1- (Benzyloxy) -2,3- dimethoxybenzene} ( Compound 37): The reaction was carried out in acetone solvent. Synthesis and separation were carried out following the synthesis and separation of compound 12. Yield: 96%; Colorless liquid; Rf = 0.46 (EtOAc: hexane = 1: 3); 1 H NMR (300 MHz, CDCl 3 )? 7.43-7.26 (5H, m), 6.92 (1H, t, J = 8.3 Hz), 6.60-6.55 3H, s), 3.85 (3H, s); 13 C NMR (75 MHz, CDCl 3) δ 153.8. 152.8. 137.4. 128.7. 128.0. 127.4. 123.7. 107.8. 105.9. 71.3. 61.2. 56.4

Grigny  General procedure of reaction:

To a solution of aldehyde (1.0 mmol) in anhydrous THF (6 mL) and stirring, a THF solution (1.2 mL, 1.2 mmol) of 1.0 M vinylmagnesium bromide was gradually added at 0 ° C. The reaction mixture was stirred at room temperature for two hours. After completion of the reaction, a water-soluble saturated NH 4 Cl solution (2 mL) was slowly added and the mixture was stirred for 15 minutes. The reaction mixture was extracted with EtOAc (2 x 35 mL). The combined organic solvent layers were washed with brine (2 x 40 mL), dried over anhydrous Na 2 SO 4 and concentrated in vacuo. The crude compound was purified by column chromatography (EtOAc: Hexane = 1: 5-1: 4) to obtain the compound.

1-phenyl-prop-2-en-1-ol{1- Phenylprop -2-en-1- ol} ( Compound 19): Yield: 78%; Colorless liquid; Rf = 0.50 (EtOAc: hexane = 1: 3); 1 H NMR (300 MHz, CDCl 3) δ 7.35-7.23 (5H, m), 6.08-5.97 (1H, m), 5.33 (1H, d, J = 17.1 Hz), 5.20-5.16 (2H, m), 2.06 (1H, doublet, J = 3.6 Hz); 13 C NMR (75 MHz, CDCl 3 )? 142.4, 170.0, 128.4, 127.6, 126.2, 115.0, 75.3.

1- (2- (benzyloxy) phenyl) prop-2-en-1-ol{1- (2- (Benzyloxy) phenyl ) prop-2-en-1-ol} ( Compound 33): Yield: 82.3 %; Colorless liquid; Rf = 0.35 (EtOAc: hexane = 1: 5); 1 H NMR (300 MHz, CDCl 3) δ 7.41-7.30 (6H, m), 7.22 (1H, td, J = 7.5, 1.5 Hz), 6.96 (1H, t, J = 7.5 Hz), 6.93 (1H, d, J = 8.1 Hz), , 6.17-6.06 (1H, m), 5.42 (1H, s) 5.28 (1H, d, J = 17.1 Hz), 5.16 (1H, d, J = 10.8 Hz), 5.09 ( 2H, s), 2.77 (1H, d, J = 5.4 Hz); 13 C NMR (75 MHz, CDCl 3 )? 155.8, 139.5, 136.6, 131.2, 128.6, 128.5, 127.9, 127.4, 127.3, 121.2, 114.4, 112.1, 71.5, 70.4.

1- (3- (benzyloxy) -2-methoxyphenyl) prop-2-en-1-ol{1- (3- (Benzyloxy) -2 -methoxyphenyl) prop-2-en-1-ol} (Compound 34): Yield: 94.5%; Kite yellow liquid; Rf = 0.26 (EtOAc: hexane = 1: 5); 1 H NMR (300 MHz, CDCl 3 )? 7.44-7.28 (5H, m) 7.036.89 (3H, m), 6.15-6.04 , J = 17.1), 5.18 (1H, dd, J = 10.4, 1.1 Hz) 5.10 (2H, s), 2.80 (1H, s); 13 C NMR (75 MHz, CDCl 3 )? 151.7, 140.2, 136.9, 136.4, 128.5, 127.9, 127.2, 124.0, 119.8, 114.4, 114.0, 71.5, 71.0, 61.1.

1- (2- (benzyloxy) -5-methoxy-phenyl) prop-2-en-1-ol{1- (2- (Benzyloxy) -5 -methoxyphenyl) prop-2-en-1-ol} (Compound 35): Yield: 89.5%; Kite yellow liquid; Rf = 0.23 (EtOAc: hexane = 1: 5); 1 H NMR (300 MHz, CDCl 3) δ 7.38-7.23 (5H, m), 6.90 (1H, d, J = 3.0 Hz), 6.87 (1H, d, J = 9.0 Hz), 6.75 (1H, dd, J = 9.0, 3.0 Hz), 6.15-6.04 (1H, m,), 5.42 (1H, t, J = 5.4 Hz) 5.29 (1H, d, J = 17.1 Hz), 5.16 (1H, d, J = 10.2 Hz), 5.04 (2H, s), 3.76 (3H, s), 2.73 (1H, d, J = 5.7 Hz); 13 C NMR (75 MHz, CDCl 3 )? 154.2, 150.1, 139.5, 17.1, 132.5, 128.8, 128.2, 127.6, 114.9, 113.7, 113.6, 113.3, 71.8, 71.3, 56.0.

Fried - Kraft  Alkylation reaction Friedel -Crafts alkylation ) The general procedure for:

Cu (OTf) 2 (0.036 g, 0.1 mmol) and molecular sieves (0.15 mmol) were added to a solution of allyl alcohol (1.0 mmol) and compound 21 (0.392 g, 2.0 mmol) in anhydrous CH 2 Cl 2 4 A o (0.39 g) was added at 0 ° C under a nitrogen atmosphere. The reaction mixture was stirred for 5-6 hours. After completion of the reaction, aqueous saturated NH 4 Cl solution (2 mL) was slowly added and extracted with CH 2 Cl 2 (2 x 30 mL). The combined organic solvent layers were washed with brine (2 x 30 mL), dried over anhydrous Na 2 SO 4 and concentrated in vacuo. The crude compound was purified by column chromatography (EtOAc: Hexane = 1: 20-1: 10). [Inventor note: Friedel-Craft reaction of allyl alcohol and compound 37 was carried out at room temperature for 3 hours instead of 0 ° C].

1- (benzyloxy) -4-cinnamyl-2,3-dimethoxy benzene 1- {(Benzyloxy) -4-cinnamyl} -2,3-dimethoxybenzene (Compound 38): Yield: 61%; Colorless liquid; Rf = 0.65 (EtOAc: hexane = 1: 5); 1 H NMR (300 MHz, CDCl 3) δ 7.46-7.16 (10H, m), 6.87 (1H, d, J = 8.7 Hz), 6.64 (1H, d, J = 8.7 Hz), 6.35 (1H, d, J = 15.6 Hz), 6.22 ( 1H, dt, J = 15.6, 6.6 Hz), 5.06 (2H, s), 3.89 (3H, s), 3.86 (3H, s), 3.44 (2H, d, J = 6.6 Hz); 13 C NMR (75 MHz, CDCl 3) δ 151.7, 151.2, 137.4, 137.0, 130.5, 129.2, 128.4, 128.3, 127.7, 127.1, 126.8, 126.5, 126.3, 125.9, 123.8, 109.3, 70.9, 61.1, 60.8, 33.1

(E) -1- (benzyloxy) -4- (3- (2- (benzyloxy) phenyl) allyl) -2,3-dimethoxy-benzene {(E) -1- (Benzyloxy) -4- ( 3- (2- (benzyloxy) phenyl) allyl) -2,3-dimethoxybenzene} (Compound 39): Rf = 0.65 (EtOAc: hexane = 1: 5); 1 H NMR (300 MHz, CDCl 3) δ 7.44-723 (11H, m), 7.13 (1H, td, J = 8.4, 1.8 Hz), 6.90-6.78 (4H, m), 6.63 (1H, d, J = 8.7 Hz), 6.33 (1H , dt, J = 15.9, 6.9 Hz), 5.07 (2H, s), 5.05 (2H, s), 3.88 (3H, s), 3.85 (3H, s), 3.49 (2H , dd, J = 6.9,1.2 Hz); 13 C NMR (75 MHz, CDCl 3) δ 155.7, 152.1, 151.5, 143.3, 137.5, 137.4, 130.3, 129.1, 128.7, 128.5, 128.1, 128.0, 127.9, 127.5, 127.4, 127.3, 126.8, 125.7, 124.2, 121.2 , 112.8, 109.9, 71.4, 70.7, 61.4, 61.2, 33.8.

(E) -1- (benzyloxy) -4- (3- (3- (benzyloxy) -2-methoxyphenyl) allyl) -2,3-dimethoxy-benzene {(E) -1- (Benzyloxy ) -4- (3- ( benzyloxy ) -2- methoxyphenyl ) allyl ) -2,3 -dimethoxybenzene} (Compound 40): Yield: 32%; Colorless liquid; Rf = 0.52 (EtOAc: hexane = 1: 5); 1 H NMR (300 MHz, CDCl 3) δ 7.49-7.31 (10H, m), 7.11 (1H, dd, J = 7.8, 0.9 Hz), 6.96 (1H, t, J = 7.8 Hz), 6.88 (1H, d, J = 8.4 Hz), 6.83 (1H, dd, J = 7.8, 0.9 Hz), 6.82 (1H, d, J = 15.9 Hz), 6.70 (1H, d, J = 8.4 Hz), 6.38 (1H, dt, J = 15.9, 7.0 Hz), 5.14 (4H, s), 3.95 (6H, s), 3.88 (3H, s), 3.57 (2H, d, J = 7.0 Hz); 13 C NMR (75 MHz, CDCl 3) δ 152.0, 151.8, 151.3, 147.0, 143.0, 137.2, 137.1, 132.0, 128.3, 127.7, 127.2, 127.1, 126.8, 124.9, 123.8, 123.7, 118.6, 113.1, 109.7, 71.2 , 70.9, 61.1, 61.0, 60.8, 33.5.

(E) -1- (benzyloxy) -4- (3- (2- (benzyloxy) -5-methoxy-phenyl) allyl) -2,3-dimethoxy-benzene {(E) -1- (Benzyloxy ) -4- (3- (2- ( benzyloxy ) -5- methoxyphenyl ) allyl ) -2,3 -dimethoxybenzene} (Compound 41): Yield: 32%; Colorless liquid; Rf = 0.56 (EtOAc: hexane = 1: 5); 1 H NMR (300 MHz, CDCl 3) δ 7.48-7.30 (10H, m), 7.02 (1H, d, J = 2.7 Hz), 6.85 (1H, d, J = 8.4 Hz), 6.85 (1H, d, J = 8.4 Hz), 6.81 ( 1H, d, J = 15.3 Hz), 6.71 (1H, dd, J = 8.4, 2.7 Hz), 6.36 (1H, dt, J = 15.6, 6.9 Hz), 6.67 (1H, d, J = 8.4 Hz), 5.11 (2H, s), 5.02 (2H, s), 3.93 (3H, s), 3.89 (3H, s), 3.78 (3H, s), 3.53 (2H, d, J = 6.9 Hz); 13 C NMR (75 MHz, CDCl 3) δ 154.3, 152.1, 151.6, 150.2, 143.3, 137.6, 137.5, 130.6, 128.7, 128.6, 128.6, 128.0, 127.9, 127.5, 127.4, 127.1, 125.5, 124.2, 114.7, 113.3 , 112.1, 109.9, 71.8, 71.5, 61.4, 61.1, 56.0, 33.7.

Benzyl group Deprotected  Typical procedure:

BCl 3 solution (1.0 M in CH 2 Cl 2 , 0.375 mL, 0) was added to a stirred solution of 1,3-substituted diphenylpropene (0.15 mmol) protected with benzyl group in anhydrous CH 2 Cl 2 375 mmol, 2.5 eq.) Was added slowly at -40 < 0 > C under a nitrogen atmosphere. The reaction mixture was stirred at -40 < 0 > C for one hour. After completion of the reaction, MeOH (1 mL) was slowly added to cool excess BCl 3 , and the solvent was removed under reduced pressure. H 2 O (5 mL) and CH 2 Cl 2 (15 mL) were added to the crude compound and the two layers were separated. The aqueous layer was extracted with CH 2 Cl 2 (2 x 25 mL), dried over anhydrous Na 2 SO 4 and concentrated in vacuo. The crude compound was purified by column chromatography (EtOAc: Hexane = 1: 4-1: 3). [Inventor Note: BCl 3 u was used instead of 2.5 equivalents but 1.5 equivalents to prepare compound 5 from compound 38.

4-cinnamyl-2,3-methoxyphenol {4-Cinnamyl-2,3-dimethoxyphenol} (mucronustyrene) (compound 5): Yield: 89%; Colorless liquid; Rf = 0.49 (EtOAc: hexane = 1: 1); 1 H NMR (300 MHz, CDCl 3) δ 7.34-7.13 (5H, m), 6.81 (1H, d, J = 8.4 Hz), 6.43 (1H, d, J = 15.6 Hz), 6.40 (1H, d, J = 8.4 Hz), 6.35 ( 1H, dt, J = 15.6, 5.7 Hz), 5.92 (1H, s), 3.89 (3H, s), 3.82 (3H, s), 3.49 (2H, d, J = 5.7 Hz); 13 C NMR (75 MHz, CDCl 3 )? 150.7, 147.1, 137.6, 135.4, 130.5, 128.7, 128.3, 126.8, 126.0, 127.1, 119.2, 103.6, 60.9, 55.9, 32.8; EI-MS m / z 270 (M < + > , base), 239, 207.

(E) -4- (3- (2- hydroxyphenyl) allyl) -2,3-dimethoxy-phenol {(E) -4- (3- ( 2-Hydroxyphenyl) allyl) -2,3-dimethoxyphenol } ( mucronulasthene ) (Compound 6): Yield: 98%; Kite yellow liquid; Rf = 0.18 (EtOAc: hexane = 1: 3); 1 H NMR (300 MHz, CDCl 3) δ 7.30 (1H, dd, J = 7.8, 1.5 Hz), 7.08 (1H, td, J = 7.8, 1.5 Hz), 6.86 (1H, d, J = 7.8 Hz) , 6.84 (1H, d, J = 8.4 Hz), 6.77 (1H, dd, J = 7.8, 1.2 Hz), 6.68 (1H, d, J = 8.4 Hz), 6.60 (1H, d, J = 15.6 Hz) , 6.29 (1H, dt, J = 15.6, 6.9 Hz), 5.68 (1H, s), 5.20 (1H, s), 3.93 (3H, s), 3.86 (3H, s), 3.50 (2H, dd, J = 6.9, 1.5 Hz); 13 C NMR (75 MHz, CDCl 3) δ 152.8, 150.9, 148.4, 140.1, 132.2, 128.3, 127.7, 125.5, 125.2, 125.1, 124.9, 121.0, 115.9, 110.5, 60.9, 60.7, 33.8; EI-MS m / z 286 (M < + > , base), 255, 223.

(E) -4- (3- (3- hydroxy-2-methoxyphenyl) allyl) -2,3-dimethoxy-phenol {(E) -4- (3- ( 3-Hydroxy-2-methoxyphenyl ) allyl) -2,3 -dimethoxyphenol} ( dalberatin A) (Compound 7): Yield: 91%; Colorless liquid; Rf = 0.56 (EtOAc: hexane = 1: 1); 1 H NMR (300 MHz, CDCl 3) δ 6.95 (1H, dd, J = 7.8, 2.4 Hz), 6.91 (1H, t, J = 7.8 Hz), 6.81 (1H, d, J = 8.4 Hz), 6.80 (1H, dd, J = 7.8 , 2.4 Hz), 6.66 (1H, d, J = 8.4 Hz), 6.58 (1H, d, J = 15.9 Hz), 6.34 (1H, dt, J = 15.9, 6.6 Hz) , 5.81 (1H, s), 5.77 (1H, s), 3.90 (3H, s), 3.85 (3H, s), 3.74 (3H, s), 3.49 (2H, dd, J = 6.6, 0.9 Hz); 13 C NMR (75 MHz, CDCl 3) δ 150.6, 148.9, 148.1, 144.2, 139.8, 131.4, 130.8, 125.1, 124.6, 124.5, 118.0, 114.0, 110.3, 61.4, 60.7, 60.5, 33.3; EI-MS m / z 316 (M < + > , base), 285, 253.

( E ) -4- (3- (2- Hydroxy -5- Methoxyphenyl ) Allyl) -2,3- Dimethoxyphenol  {( E ) -4- (3- (2-Hydroxy-5-methoxyphenyl) allyl) -2,3-dimethoxyphenol} ( dalberatin  B) (Compound 8):

Yield: 94%; Colorless liquid; Rf = 0.52 (EtOAc: hexane = 1: 1); 1 H NMR (300 MHz, CDCl 3) δ 6.84 (1H, d, J = 3.0 Hz), 6.82 (1H, d, J = 8.4 Hz), 6.69 (1H, d, J = 8.4 Hz), 6.66 (1H , d, J = 8.4 Hz) , 6.65 (1H, dd, J = 8.4, 3.0 Hz), 6.57 (1H, d, J = 15.6 Hz), 6.27 (1H, dt, J = 15.6, 6.6 Hz), 5.64 (1H, s), 4.76 (1H, s), 3.92 (3H, s), 3.85 (3H, s), 3.74 (3H, s), 3.49 (2H, d, J = 6.6 Hz); 13 C NMR (75 MHz, CDCl 3) δ 154.0, 150.9, 148.4, 146.9, 140.1, 132.3, 125.7, 125.4, 125.2, 124.9, 116.7, 114.1, 112.6, 110.5, 60.9, 60.7, 56.1, 33.7; EI-MS m / z 316 (M < + > , base), 285, 253.

Figure 112016009145662-pat00001

Claims (4)

A) 2,3-dimethoxy compounds represented by compound 37 represented by the formula of phenol 37 produced by gasification protected with benzyl by the general formula 52 19, Cu (OTf within each of CH 2 Cl 2 with 33 to 35) 2 / 4 A MS to give 1,3-substituted diphenylpropene compounds 38 to 41 protected with a benzyl group represented by the formula (53) to obtain a compound 38 from the compound 19 and a compound 38 from the compound 33 39 from compound 34, compound 40 from compound 34, and compound 41 from compound 35; And
B) One of the 1,3-substituted diphenylpropene compounds 38 to 41 obtained in the above step a) was reacted with 1.0 M BCl 3 solution to give benzyl group deprotection to give compounds 5 to 8 of formula 54, compound 5 from compound 38, compound 6 from compound 39, compound 7 from compound 40, compound 7 from compound 39, 41. A process for synthesizing 1,3-substituted diphenylpropene comprising the steps of:
(52)
Figure 112017049129287-pat00002

≪ Formula 53 >
Figure 112017049129287-pat00003

(54)
Figure 112017049129287-pat00004

(37)
Figure 112017049129287-pat00005

 The method according to claim 1,
Compounds 33 to 35 of the above a)
a) Aldehyde compounds 29, 10 and 11 represented by the formula 51 are protected with a benzyl group to give the aldehyde compounds 30 to 32 represented by the formula 51, the compound 30 from the compound 29, the compound 31 from the compound 10, the compound 11 ≪ / RTI > And
b) The aldehyde compound 30-32 protected with the benzyl group obtained in the above step a) is respectively subjected to Grignard reaction with vinyl magnesium bromide to obtain the allyl alcohol compound 33-35 represented by the formula 52, the compound 33 from the compound 30, the compound 31 To obtain compound 34 from compound 32 and compound 35 from compound 32. The 1,3-substituted diphenylpropene synthesis method according to claim 1,
<Formula 51>
Figure 112017049129287-pat00006

 delete delete
KR1020160010208A 2016-01-27 2016-01-27 Synthetic method of 1,3-substituted diphenylpropenes KR101747694B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KR1020160010208A KR101747694B1 (en) 2016-01-27 2016-01-27 Synthetic method of 1,3-substituted diphenylpropenes

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
KR1020160010208A KR101747694B1 (en) 2016-01-27 2016-01-27 Synthetic method of 1,3-substituted diphenylpropenes

Publications (1)

Publication Number Publication Date
KR101747694B1 true KR101747694B1 (en) 2017-06-15

Family

ID=59217619

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020160010208A KR101747694B1 (en) 2016-01-27 2016-01-27 Synthetic method of 1,3-substituted diphenylpropenes

Country Status (1)

Country Link
KR (1) KR101747694B1 (en)

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Angew. Chem. Int. Ed. 2013, vol 52, pp. 9509-9512.*
Organic Letters, 2008, vol 10, pp. 2967-2970.*
Tetrahedron Letters, 2005, vol 46, pp.3871-3874.*

Similar Documents

Publication Publication Date Title
Sun et al. Efficient synthesis of natural polyphenolic stilbenes: resveratrol, piceatannol and oxyresveratrol
Enders et al. Asymmetric synthesis of functionalized chromans via a one-pot organocatalytic domino Michael-hemiacetalization or-lactonization and dehydration sequence
Liu et al. Regioselective Synthesis of Aurone Derivatives via PBu3‐Catalyzed Cyclization of 2‐Alkynoylphenols
Maheswara et al. Two new homoisoflavonoids from Caesalpinia pulcherrima
Takashima et al. Synthetic access to optically active isoflavans by using allylic substitution
Javed et al. Enantioselective syntheses of (+)-and (−)-brazilin
RU2745062C2 (en) Producing method of long-chain alcohol of high purity cyclohexenone
KR101747694B1 (en) Synthetic method of 1,3-substituted diphenylpropenes
Dao et al. Synthesis and biological activities of 8-arylflavones
Lee et al. A novel synthesis of flavanones from 2-hydroxybenzoic acids
KR101747693B1 (en) Synthetic method of 1,3-substituted Diphenylpropenes
KR101774224B1 (en) Synthetic method for rugchalcone A, B and their derivatives and their anti-inflammatory use
Jung et al. Syntheses and Anti-inflammatory Activity of Natural 1, 3-Diarylpropenes
Li A facile synthesis and application of ethyl 6-(bromomethyl)-[1, 3] dioxolo [4, 5-g] quinoline-7-carboxylate
OHISHI et al. Reactions of salicylaldehydes with bromonitromethane
Ashok et al. Solvent-free microwave assisted synthesis of (E)-1-{3-[2-(9-Ethyl-9 H-carbazol-3-yl) vinyl] benzofuran-2-yl}-2, 2-dimethylpropan-1-ones and their antimicrobial activity
KR102563123B1 (en) Method of manufacturing fisetin or its derivatives
Gaikwad et al. Synthesis of some novel chalcones of phthalimidoester possessing good anti-inflammatory and antimicrobial activity
HAHNVAJANAwONg et al. Reductive ring opening of 3, 5-bis (2-arylethenyl) isoxazoles with molybdenum hexacarbonyl: A novel route to symmetrical and unsymmetrical curcumin derivatives
Kulkarni et al. Synthesis of dibenzylidene acetone via aldol condensation of diacetone alcohol with substituted benzaldehydes
JP2005281215A (en) Optical resolution reagent consisting of optically active spiro compound
Yamaguchi et al. Acylations of 2, 2-dimethyl-2H-chromenes.
Xia et al. Efficient synthesis of biologically interesting natural pyranochalcones from Mallotus philippensis and their unnatural derivatives
KR101739728B1 (en) Synthetic method for moracin F using Sonogashira coupling reaction
Kamat et al. A convenient one-pot synthesis of 4-methyl-3-phenyl-, 3-aryl-and 3-aryl-4-phenylcoumarins

Legal Events

Date Code Title Description
E902 Notification of reason for refusal
E701 Decision to grant or registration of patent right
GRNT Written decision to grant