Paratocarpin B的全合成

2012 年第20卷合成化学Vol.20, 2012第5期, 578 ~581Chinese Joumal of Synthetic ChemistryNo.5, 578 ~581●快递论文●Paratocarpin B的全合成落俊山,杨金会,王金荣,黄文倩,郭冬冬，李红俊，张玉恒(宁夏大学天然气转化国家重点实验室培育基地,宁夏银川750021)摘要:以对羟基苯甲醛和2,4-二羟基苯乙酮为起始原料,经过C异戊烯基化保护酚羟基、羟醛缩合催化环化、去保护基等反应,以18. 4%的总收率首次完成了天然异戊烯基查尔酮Paratocapin B的全合成,中间体3',4'-(2,2-二甲基吡喃) -2'-羟基3-异戊烯基4-甲氧甲氧基查尔酮( 10)未见文献报导,其结构经'H NMR, IR和MS表征。关键词: Paratocarpin B;查尔酮;异戊烯基查尔酮;合成中图分类号: 0625. 1文献标识码: A文章编号: 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、查尔酮类化合物是-类存在于甘草、红花等/0H药用植物中的天然有机化合物,由于其分子结构的柔性较大,能与不同的受体结合，因此具有广泛0H 0的生物活性[1-3。Paratocarpin B(1)查尔酮是合成黄酮类化合物的中间体。本研Chart 1究小组(4-6]长期从事黄烷酮类化合物的研究,合又从甘草中分离出1,并发现其具有抗氧化活性成了一些此类天然产物,每种化合物都要以查尔(ICso=2.3 μmol●L-1)。目前1的全合成未见.酮为中间体才能得到最终产物。天然异戍烯基查文献报道,因此1的全合成研究不仅具有重要的尔酮Paratocarpin B(1, Chart 1)是1995年日本学理论意义,而且具有潜在的药用前景。者Yoshio Hano 等[门] 从印度的桑科植物中本文以廉价的2 ,4-二羟基苯乙酮(4)和对羟首次分离出来的,2007年Young-won CHIN等[8]收稿日期: 2011-10-18基金项目:国家自然科学基金赞助项目(20962016);教育部“新世纪优秀人才中国煤化工;宁夏自然科学基金资助项目(NZ106)HCNMHG作者简介:落俊山(1984 - ) ,男,汉族,山西朔州人,硕土研究生,主要从事天然产物的全合成研究。通信联系人:杨金会,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)为起始原料,经过C~异戊烯基化、保在反应瓶中加人KOH 560 mg( 10 mmol)的水护酚羟基羟醛缩合、催化环化、去保护基等反应,(10 mL)溶液,冷却至0 C ,搅拌下加入2,4-二羟首次以17.0%的总收率首次完成了1的全合成基苯乙酮(4) 760 mg(5 mmol) ,缓慢滴加3 0.6(Scheme 1)。中间体3' ,4'-(2,2-二甲基吡喃)-mL(5mmol),滴毕,反应1h;自然升至室温避光2'.羟基-3-异戊烯基4-甲氧甲氧基查尔酮(10)为反应8h。用3 mol●L- !盐酸调至pH <3,用乙酸新化合物,其结构经H NMR, IR和MS表征。乙酯(3 x30 mL)萃取,合并有机相合,依次用水、饱和食盐水洗涤,无水硫酸钠干燥,减压蒸除溶剂1实验部分后经硅胶柱层析[洗脱剂:A= V(石油醚) : V(乙酸乙酯) =7 :1]分离得白色固体5385 mg(同时1.1 仪器与试剂X-5型熔点仪(温度计未校正);BrukerAM-得到2,4-二羟基5-异戊烯基苯乙酮107 mg, 2-羟400 MHz型核磁共振仪( CDCl3为溶剂,TMS为内基4-异戊烯氧基苯乙酮150 mg,回收原料90标) ;IFT-IR-8430S型红外光谱仪(KBr压片);mg) ,产率35%, m.p.155 C ~158 C; 'H NMRδ: 1.64, 1. 77(s, 6H, CH;), 2. 53(s, 3H,5975C型质谱仪。硅胶(200目~300目)和GF254硅胶,青岛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海洋化工厂;所用试剂均为分析纯。Hz, 1H, ArH), 7.64 (d,J=8.8 Hz, 1H, ArH),2.1合成13.11(s, 1H, 0H)。(1)异戊烯基溴(3)的合成[9] .(3) 2,2-二甲基5-羟基6-乙酰基-2H-1.苯并在反应瓶中加入异戊烯基醇(2) 2 mL( 19.7吡喃(6)的合成mmol)的乙醚(20 mL)溶液,搅拌下于室温滴加吡在反应瓶中加人5 440 mg(4. 0 mmol)的苯啶0.1 mL,滴毕,冷却至0 C ,剧烈搅拌下缓慢滴(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) ,滴毕,反应(DDQ) 454 mg(4. 0 mmol),搅拌下回流反应51 h。倾入冰水中,用乙醚(3 x30 mL)萃取,合并min。冷却至室温,加水,用乙酸乙酯(3 x20 mL)有机相,依次用水、饱和食盐水洗涤,无水硫酸镁萃取,合并有机相,依次用水、饱和食盐水洗涤,无干燥,蒸除有机溶剂得浅黄色液体3,避光低温储水硫酸钠干慢VC「中国煤化玉碓胶柱层析存备用。(洗脱剂:ATITHCNMHG6 367.4 mg,(2) 2 ,4-二羟基-3-异戊烯基苯乙酮(5)的合产率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,合成化学Vol. 20, 2012J=10.0 Hz, 1H, =CH), 6.33(dd, J=8.8 Hz,反应24h。倾人冰水中,用3 mol●L~ '盐酸调至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,合并有机Hz, 1H，= CH), 7.51(d, J=8.8 Hz, 1H,相,依次用蒸馏水、饱和食盐水洗涤,无水硫酸钠ArH), 12.99(s, 1H, 0H); IRv: 3 446, 2 974,干燥，减压蒸去溶剂后经硅胶柱层析(洗脱剂:1 627, 1 365, 1 263, 1 052, 798 cm~。A=8:1)分离得淡黄色黏稠物10 449 mg, 产率(4) 3-异戊烯基4-羟基苯甲醛(8)的合成75%; 'H NMR 8: 1. 76, 1.47(s, 12H, CH;),在反应瓶中加入KOH 560 mg( 10 mmol)的水3.36(d, J=7.2 Hz, 2H, CH2), 3. 49(s, 3H,( 10 mL)溶液,冷却至0 C ,搅拌下加入对羟基苯0CH3), 5.26(s, 2H, 0CH20), 5.30(t, J=7.2甲醛(7) 610 mg(5 mmol) ,缓慢滴加31.2 mLHz, 1H, =CH), 5.59(d, J=10.0 Hz, 1H, =C(10 mmol)滴毕,反应1 h;自然升至室温避光反H), 6.39(dd, J=8.8 Hz, 0.4 Hz, 1H, ArH),应8h。用3 mol. L-1盐酸调至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,合并有机相,依次用水、饱和.8.4 Hz, 1H, ArH), 7.41 ~7. 48(m, 3H, ArH,食盐水洗涤,无水硫酸钠干燥,减压蒸除溶剂后经=CH), 7.73(d, J=8.8 Hz, 1H, ArH), 7. 84硅胶柱层析(洗脱剂:A =7 :1)分离得无色油状(d, J=15.2 Hz, 1H, =CH), 13. 82(s, 1H,液体8323 mg(回收原料230 mg),产率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,在反应瓶中依次加入10 200 mg (0.461H, 0H), 9. 80(s, 1H，CHO); IR v: 3 264，mmol) 的甲醇( 10 mL)溶液和对甲基苯磺酸87.42966,1693,1591,1503,1430,1299,1220,mg(0.46mmol)，搅拌下于室温反应至终点(TLC1 132, 1 081, 979, 812, 630 cm~'。跟踪)。加少量水,用乙酸乙酯(3 x20 mL)萃敢,(5) 4-甲氧甲氧基3~异戊烯基苯甲醛(9)的合并有机相,依次用蒸馏水、饱和食盐水洗涤,无合成水硫酸镁干燥,减压蒸去溶剂后经硅胶柱层析在反应瓶中加入8190 mg( 1 mmol)的干燥丙(洗脱剂:A=6 :1)分离得黄色油状液体1 139酮( 10 mL)溶液,剧烈搅拌下加入无水K,CO3 166 mg,产率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),回流反应30 min。J=7.2 Hz, 1H, =CH), 5.53(s, 1H, ArH),冷却至室温,抽滤,滤液减压蒸去溶剂后经硅胶柱5. 59(d,J=10.0Hz, 1H, =CH), 6. 38(dd, J=层析(洗脱剂:A=14 :1)分离得无色油状液体98.8 Hz, 0.4 Hz, 1H, ArH), 6.76(d, J=10.0213 mg,产率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")在反应瓶中依次加人乙醇1 mL, 6 300 mg2结果与讨论(1. 38 mmol)和9262 mg( 1.38mmol)，搅拌使其本文中国煤化工料,在氢氧化溶解;冰水浴冷却至0 C ,缓慢滴加冷却至0 C的钾/水的条;MYHCNMHG,分别以35%K0H3.8 g(69 mmol)的水(2 mL)/乙醇(2. 5和34%的产率得到单C异戊烯基化产物5和8;mL)溶液，氮气保护下反应1 h;自然升至室温，.第5期落俊山等:Paratocarpin B的全合成一5815在DDQ作用下关环，以83%的产率制得6(在(士)-abysinoflavanone V [J]. 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