Paratocarpin B的全合成

2012 年第20卷合成化學(xué)Vol.20, 2012第5期, 578 ~581Chinese Joumal of Synthetic ChemistryNo.5, 578 ~581●快遞論文●Paratocarpin B的全合成落俊山,楊金會(huì ),王金榮,黃文倩,郭冬冬，李紅俊，張玉恒(寧夏大學(xué)天然氣轉化國家重點(diǎn)實(shí)驗室培育基地,寧夏銀川750021)摘要:以對羥基苯甲醛和2,4-二羥基苯乙酮為起始原料,經(jīng)過(guò)C異戊烯基化保護酚羥基、羥醛縮合催化環(huán)化、去保護基等反應,以18. 4%的總收率首次完成了天然異戊烯基查爾酮Paratocapin B的全合成,中間體3',4'-(2,2-二甲基吡喃) -2'-羥基3-異戊烯基4-甲氧甲氧基查爾酮( 10)未見(jiàn)文獻報導,其結構經(jīng)'H NMR, IR和MS表征。關(guān)鍵詞: Paratocarpin B;查爾酮;異戊烯基查爾酮;合成中圖分類(lèi)號: 0625. 1文獻標識碼: A文章編號: 105-1511 (2012)05-0578-04Total Synthesis of Paratocarpin BLUO Jun-shan，YANC Jin-hui，WANG Jin-rong,HUANG Wen-qian，GUO Dong-dong，LI Hong-jun，ZHANG Yu-heng( Stste Key Laboratory Cultivation Base of Natural Cas Conversion, Ningxia University , Yinchuan 750021 , China)Abstract: The total synthesis of natural Paratocarpin B was first achieved through C prenylation, pro-tection of phenolic hydroxyl group, aldol condensation, cyclization and deprotection from 4-hydroxy-benzaldehyde and 2 ,4-dihydroxyacetophenone in total yield of 18. 4% . Intermediate 10 was new com-pound. The structures of new compounds were characterized by 'H NMR, IR and MS.Keywords: Paratocarpin B; chalcone; prenylchalcone ; synthesis、查爾酮類(lèi)化合物是-類(lèi)存在于甘草、紅花等/0H藥用植物中的天然有機化合物,由于其分子結構的柔性較大,能與不同的受體結合，因此具有廣泛0H 0的生物活性[1-3。Paratocarpin B(1)查爾酮是合成黃酮類(lèi)化合物的中間體。本研Chart 1究小組(4-6]長(cháng)期從事黃烷酮類(lèi)化合物的研究,合又從甘草中分離出1,并發(fā)現其具有抗氧化活性成了一些此類(lèi)天然產(chǎn)物,每種化合物都要以查爾(ICso=2.3 μmol●L-1)。目前1的全合成未見(jiàn).酮為中間體才能得到最終產(chǎn)物。天然異戍烯基查文獻報道,因此1的全合成研究不僅具有重要的爾酮Paratocarpin B(1, Chart 1)是1995年日本學(xué)理論意義,而且具有潛在的藥用前景。者Yoshio Hano 等[門(mén)] 從印度的?？浦参镏斜疚囊粤畠r(jià)的2 ,4-二羥基苯乙酮(4)和對羥首次分離出來(lái)的,2007年Young-won CHIN等[8]收稿日期: 2011-10-18基金項目:國家自然科學(xué)基金贊助項目(20962016);教育部“新世紀優(yōu)秀人才中國煤化工;寧夏自然科學(xué)基金資助項目(NZ106)HCNMHG作者簡(jiǎn)介:落俊山(1984 - ) ,男,漢族,山西朔州人,碩土研究生,主要從事天然產(chǎn)物的全合成研究。通信聯(lián)系人:楊金會(huì ),博士,教授, Tel. 0951 -2062246, E-mail:; yang jh@ nou. edu. cn第5期落俊山等:Partocarpin B的全合成- 579-PBrs, aether, pyridine.n,1h3HO~3, KOH/H20DDQ, benzene35%reflux, 5 min, 90%OH 00H 0H 3, KOH/H200HMOMCI, K,CO334%acetone, refux, 91%80MOM 6, KOHH2O-EtOHX 0OMOMp-TeOH, MeOH→10v IYN2, 75%nt, 78%90H010Scheme 1基苯甲醛(7)為起始原料,經(jīng)過(guò)C~異戊烯基化、保在反應瓶中加人KOH 560 mg( 10 mmol)的水護酚羥基羥醛縮合、催化環(huán)化、去保護基等反應,(10 mL)溶液,冷卻至0 C ,攪拌下加入2,4-二羥首次以17.0%的總收率首次完成了1的全合成基苯乙酮(4) 760 mg(5 mmol) ,緩慢滴加3 0.6(Scheme 1)。中間體3' ,4'-(2,2-二甲基吡喃)-mL(5mmol),滴畢,反應1h;自然升至室溫避光2'.羥基-3-異戊烯基4-甲氧甲氧基查爾酮(10)為反應8h。用3 mol●L- !鹽酸調至pH <3,用乙酸新化合物,其結構經(jīng)H NMR, IR和MS表征。乙酯(3 x30 mL)萃取,合并有機相合,依次用水、飽和食鹽水洗滌,無(wú)水硫酸鈉干燥,減壓蒸除溶劑1實(shí)驗部分后經(jīng)硅膠柱層析[洗脫劑:A= V(石油醚) : V(乙酸乙酯) =7 :1]分離得白色固體5385 mg(同時(shí)1.1 儀器與試劑X-5型熔點(diǎn)儀(溫度計未校正);BrukerAM-得到2,4-二羥基5-異戊烯基苯乙酮107 mg, 2-羥400 MHz型核磁共振儀( CDCl3為溶劑,TMS為內基4-異戊烯氧基苯乙酮150 mg,回收原料90標) ;IFT-IR-8430S型紅外光譜儀(KBr壓片);mg) ,產(chǎn)率35%, m.p.155 C ~158 C; 'H NMRδ: 1.64, 1. 77(s, 6H, CH;), 2. 53(s, 3H,5975C型質(zhì)譜儀。硅膠(200目~300目)和GF254硅膠,青島COCHy), 3.35(d, J=7.2 Hz, 2H, CH2), 5. 26(t, J=7.2 Hz, 1H, =CH), 6.50(d, J=8.8海洋化工廠(chǎng);所用試劑均為分析純。Hz, 1H, ArH), 7.64 (d,J=8.8 Hz, 1H, ArH),2.1合成13.11(s, 1H, 0H)。(1)異戊烯基溴(3)的合成[9] .(3) 2,2-二甲基5-羥基6-乙?；?2H-1.苯并在反應瓶中加入異戊烯基醇(2) 2 mL( 19.7吡喃(6)的合成mmol)的乙醚(20 mL)溶液,攪拌下于室溫滴加吡在反應瓶中加人5 440 mg(4. 0 mmol)的苯啶0.1 mL,滴畢,冷卻至0 C ,劇烈攪拌下緩慢滴(10 mL)溶液和2,3-二氯-5 ,6-二氰基-1 ,4-苯醌加三溴化磷( PBr2) 1.9 mL(20 mmol) ,滴畢,反應(DDQ) 454 mg(4. 0 mmol),攪拌下回流反應51 h。傾入冰水中,用乙醚(3 x30 mL)萃取,合并min。冷卻至室溫,加水,用乙酸乙酯(3 x20 mL)有機相,依次用水、飽和食鹽水洗滌,無(wú)水硫酸鎂萃取,合并有機相,依次用水、飽和食鹽水洗滌,無(wú)干燥,蒸除有機溶劑得淺黃色液體3,避光低溫儲水硫酸鈉干慢VC「中國煤化玉碓膠柱層析存備用。(洗脫劑:ATITHCNMHG6 367.4 mg,(2) 2 ,4-二羥基-3-異戊烯基苯乙酮(5)的合產(chǎn)率83%，m.p.yo七~yδ L; n NMR δ: 1.45成[10](s, 6H, CH3), 2.53(s, 3H, COCH,), 5.58(d,合成化學(xué)Vol. 20, 2012J=10.0 Hz, 1H, =CH), 6.33(dd, J=8.8 Hz,反應24h。傾人冰水中,用3 mol●L~ '鹽酸調至0.8 Hz, 1H, ArH), 6. 70(dd, J=10.0 Hz, 0.8pH <2,用二氯甲烷(3 x20 mL)萃取,合并有機Hz, 1H，= CH), 7.51(d, J=8.8 Hz, 1H,相,依次用蒸餾水、飽和食鹽水洗滌,無(wú)水硫酸鈉ArH), 12.99(s, 1H, 0H); IRv: 3 446, 2 974,干燥，減壓蒸去溶劑后經(jīng)硅膠柱層析(洗脫劑:1 627, 1 365, 1 263, 1 052, 798 cm~。A=8:1)分離得淡黃色黏稠物10 449 mg, 產(chǎn)率(4) 3-異戊烯基4-羥基苯甲醛(8)的合成75%; 'H NMR 8: 1. 76, 1.47(s, 12H, CH;),在反應瓶中加入KOH 560 mg( 10 mmol)的水3.36(d, J=7.2 Hz, 2H, CH2), 3. 49(s, 3H,( 10 mL)溶液,冷卻至0 C ,攪拌下加入對羥基苯0CH3), 5.26(s, 2H, 0CH20), 5.30(t, J=7.2甲醛(7) 610 mg(5 mmol) ,緩慢滴加31.2 mLHz, 1H, =CH), 5.59(d, J=10.0 Hz, 1H, =C(10 mmol)滴畢,反應1 h;自然升至室溫避光反H), 6.39(dd, J=8.8 Hz, 0.4 Hz, 1H, ArH),應8h。用3 mol. L-1鹽酸調至pH <3,用乙酸乙6.76(d, J=10.0 Hz, 1H, =CH), 7.09(d, J=酯(3 x 30 mL)萃取,合并有機相,依次用水、飽和.8.4 Hz, 1H, ArH), 7.41 ~7. 48(m, 3H, ArH,食鹽水洗滌,無(wú)水硫酸鈉干燥,減壓蒸除溶劑后經(jīng)=CH), 7.73(d, J=8.8 Hz, 1H, ArH), 7. 84硅膠柱層析(洗脫劑:A =7 :1)分離得無(wú)色油狀(d, J=15.2 Hz, 1H, =CH), 13. 82(s, 1H,液體8323 mg(回收原料230 mg),產(chǎn)率34 %; 0H); IRv: 2929, 1 634, 1 562, 1 481, 1 358,'H NMR 8: 1.74(s, 3H, CH3), 1.77(s, 3H，1241, 1 110, 987 cm~'; EI-MS m/z(%): 434 .CH,), 3.41(d, J=7.2 Hz, 2H, CH2), 5.34(t，(14), 419(29), 290(22), 271(10), 188<(14)，J=7.2 Hz, 1H，=CH), 6.97(d, J=8. 0 Hz,187(100), 45(63)。1H, ArH), 7. 65(dd, J=2.2 Hz, 8.2 Hz, 1H,(7) 1的合成ArH), 7.69(d, J=2.0 Hz, 1H, ArH), 7. 89(s,在反應瓶中依次加入10 200 mg (0.461H, 0H), 9. 80(s, 1H，CHO); IR v: 3 264，mmol) 的甲醇( 10 mL)溶液和對甲基苯磺酸87.42966,1693,1591,1503,1430,1299,1220,mg(0.46mmol)，攪拌下于室溫反應至終點(diǎn)(TLC1 132, 1 081, 979, 812, 630 cm~'。跟蹤)。加少量水,用乙酸乙酯(3 x20 mL)萃敢,(5) 4-甲氧甲氧基3~異戊烯基苯甲醛(9)的合并有機相,依次用蒸餾水、飽和食鹽水洗滌,無(wú)合成水硫酸鎂干燥,減壓蒸去溶劑后經(jīng)硅膠柱層析在反應瓶中加入8190 mg( 1 mmol)的干燥丙(洗脫劑:A=6 :1)分離得黃色油狀液體1 139酮( 10 mL)溶液,劇烈攪拌下加入無(wú)水K,CO3 166 mg,產(chǎn)率78%; 'H NMR 8: 1. 80,1.47(s, 12H,mg(1.2mmol),完全溶解后滴加氯甲基甲基醚CH,), 3.40(d, J=7.2 Hz, 2H, CH2), 5.33(t,(MOMCl) 96 mg( 1.2 mmol),回流反應30 min。J=7.2 Hz, 1H, =CH), 5.53(s, 1H, ArH),冷卻至室溫,抽濾,濾液減壓蒸去溶劑后經(jīng)硅膠柱5. 59(d,J=10.0Hz, 1H, =CH), 6. 38(dd, J=層析(洗脫劑:A=14 :1)分離得無(wú)色油狀液體98.8 Hz, 0.4 Hz, 1H, ArH), 6.76(d, J=10.0213 mg,產(chǎn)率91%; 'H NMR 8: 1. 71(s, 3H，Hz, 1H，= CH), 6. 84(d, J=8.4 Hz, 1H,CH;), 1.74(s, 3H, CH), 3.36(d, J=7.2 Hz，ArH), 7.40 ~7.46(m, 3H, ArH, =CH), 7.732H, CH2), 3.47(s, 3H, 0CH,), 5.28 ~5.29(d, J=15.6 Hz, 1H, =CH"), 13.82 (s, 1H,(m, 3H, 0CH20, =CH), 7.15(d, J=8.0 Hz,0H); IRv: 3373, 2980, 1 627, 1 547, 1 481 ,1H, ArH), 7.67(m, 2H, ArH), 9. 86(s, 1H，1 365, 1 241, 1118, 855, 805, 688 cm~'; EI-MSCHO); IRv:2958, 1 685, 1 598, 1 496, 1 249,m/z(%): 390(18), 375(35), 203(14), 1871 154, 994, 812 cm -1(100), 77(12), 43(13)。(6) 10的合成")在反應瓶中依次加人乙醇1 mL, 6 300 mg2結果與討論(1. 38 mmol)和9262 mg( 1.38mmol)，攪拌使其本文中國煤化工料,在氫氧化溶解;冰水浴冷卻至0 C ,緩慢滴加冷卻至0 C的鉀/水的條;MYHCNMHG,分別以35%K0H3.8 g(69 mmol)的水(2 mL)/乙醇(2. 5和34%的產(chǎn)率得到單C異戊烯基化產(chǎn)物5和8;mL)溶液，氮氣保護下反應1 h;自然升至室溫，.第5期落俊山等:Paratocarpin B的全合成一5815在DDQ作用下關(guān)環(huán)，以83%的產(chǎn)率制得6(在(士)-abysinoflavanone V [J]. 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