Vol. 28高等學(xué)校化學(xué)學(xué)報(bào)No.72007年7月CHEMICAL JOURNAL OF CHINESE UNIVERSITIES1292 ~ 12966-Oxodendrolasinolide的全合成李毅',張濤,李裕林'( 1.蘭州大學(xué)有機(jī)化學(xué)研究所,功能有機(jī)分子化學(xué)國家重點(diǎn)實(shí)驗(yàn)室,蘭州730000 ;2.杭州民生藥業(yè)集團(tuán)紹興制藥有限公司, 紹興312071 )摘要以香葉醇(2)和異戊烯醇(5)為起始原料,經(jīng)過12步反應(yīng),以5.6%的總收率完成了倍半萜內(nèi)酯6-0xodendrolasinolide( 1 )的全合成.其關(guān)鍵步驟包括乙烯基二噻烷( 7 )的負(fù)離子與烯丙基氯( 4a )的區(qū)域選擇性烷基化反應(yīng)和Corey's氧化內(nèi)酯化反應(yīng).關(guān)鍵詞全合成;丁烯酸內(nèi)酯;倍半萜;區(qū)域選擇性烷基化中圖分類號(hào)0621.3文獻(xiàn)標(biāo)識(shí)碼A文章編號(hào)0251-0790( 2007 )07-1292-056-0xodendrolasinolide( 1 )是1983 年Schneider等1從被污染的Ceratocystis fimbriata和經(jīng)HgCl2處理的甜薯根組織中分離得到的一種新穎的具有法呢結(jié)構(gòu)的倍半萜內(nèi)酯天然產(chǎn)物.其結(jié)構(gòu)通過光譜方法確定.到目前為止,6-0xodendrolasinolide的全合成尚未見報(bào)道.本研究小組對(duì)該類化合物進(jìn)行了合成2-4] ,設(shè)計(jì)利用1 3-二噻烷與氯化物的區(qū)域選擇性烷基化反應(yīng)5和Corey's 氧化內(nèi)酯化反應(yīng)°1為關(guān)鍵步驟,完成了6-Oxodendrolasinolid( 1 )的全合成.合成路線見Scheme 1.些OHOPHPOTHP4aX=Cl, 4bX=1o一人。一人了.5648,4b+7- f ./^OTHPxkuto8a a product8b y product9r 10R=H1211 R=PMBQPMB314 R=PMB、15 R=HScheme 1 Synthetic routes for 6-Oxodendrolasinolidea. DHP ,P-TsOH ,CH2Cl2 ,0C ,3h,yield 100% ;b. Se02 ,pyridine , EIOH ,relux 12 h ,yield 37% ;c. PPh3 , NCS,THF ,r.t. ,5h ,yield 85% ;d. PCC ,silica gel ,CH2C2 ,3h ,yield73% ;e. 1 3-propanedithiol ,El2O- BF3 ,CHCl3 ,12h,yield97% ;f. n-BuLi , -40 C ,3 h ,then compound3, -78 C ,2 h ,yield 89% ig. HgCl2 ,CaCO3 ,yield 95% , MeOH-H20 ,elux ,0.5 h,yield94% ;h. NaBH, ,.MeOH,r.t. ,3 h yiel中國煤化工bromide , DMF ,r.t，16h,yield87% ;j PPTs ,EtOH ,55 C ,3h ,yeld91% ;k. MnO2，;. ( i)TMSCN ,cat.KCN ,18-erown6 ,CH2Cl2 ,0C ,1 h;(i)PDC ,DMF ,r.t. ,121THCNMHGH20( volume ratio 20:1),0 C ,1 h ,yield 85% in. Dess-Martin periodinane ,CH2Cl2 .r.t. ,2h ,yield 87%.收稿日期:2006-08-09.基金項(xiàng)目:國家自然科學(xué)基金(批準(zhǔn)號(hào):20072012 )資助.聯(lián)系人簡(jiǎn)介:李裕林1935 年出生),男, 教授,博士生導(dǎo)師,從事有機(jī)合成化學(xué)研究. E-mail : liyl@ lzu. edu. cnNo.7李毅等:6-Oxodendrolasinolide的全合成12931結(jié)果與討論香葉醇2經(jīng)四氫吡喃基保護(hù)后, 在SeO2/Py條件下, 以37%的產(chǎn)率得到烯丙醇(3}7] ,經(jīng)NCS/PPh,氯代[8 l得氯化物4a ,產(chǎn)率87%.同樣經(jīng)常規(guī)的碘代方法( PPh,/ Imidazole/I2 )得到碘化物4b.異戊烯醇( 5 )用PCC氧化得到醛( 6),產(chǎn)率73%.根據(jù)Seebach和Corey[9 l所報(bào)道的方法,以92%的收率得到1 3-二噻烷(7).首先,用碘化物4b )與二噻烷( 7 )進(jìn)行烷基化反應(yīng),以92%的高產(chǎn)率得到產(chǎn)物8 ,但產(chǎn)物經(jīng)'H NMR譜分析,1( 8a):r( 8bI r(a):n( γ )]的選擇性之比僅為2:1.根據(jù)文獻(xiàn)10 ]報(bào)道和“.軟硬酸堿原理"( HSAB原理y"1 ,由于13-二噻烷的a位負(fù)離子比γ位的硬度大,所以隨著離去基團(tuán)X硬度的增加I~ 98: 2的高選擇性得到烷基化產(chǎn)物8.雖然相應(yīng)的氰硅醚僅得到a烷基化產(chǎn)物,但它只適用于簡(jiǎn)單的模型體系,在較為復(fù)雜及立體位阻較大的體系中,由于碳負(fù)離子親核性的降低,產(chǎn)率-般比較低12].隨后用HgCl2和CaCO3在體積分?jǐn)?shù)為95%的甲醇溶液中水解脫除=噻烷[131,以94%的產(chǎn)率得到酮9.起初,設(shè)想將羰基保護(hù)為縮酮的形式,但是可能由于位阻的原因,無法得到羰基保護(hù)的產(chǎn)物.只好將其還原( NaBH./ MeOH )為醇10 , 產(chǎn)率92%.隨后將羥基保護(hù)為對(duì)甲氧基芐醚( 11 X PMBBr/ NaH/TBAI/DMF ),產(chǎn)率87%.在PPTS/EtOH條件下脫除THP保護(hù)基{141 ,以91%的產(chǎn)率得到醇12 ,然后用MnO2氧化得到烯丙醛13 ,產(chǎn)率84%.根據(jù)Corey's氧化內(nèi)酯化方法6] ,首先將醛13與TMSCN在KCN/ 18-Crown-6的催化下得到氰硅醚,隨后用PDC在DMF中氧化,以47%的產(chǎn)率得到丁烯酸內(nèi)酯14.用DDQ在CH2Cl2-H20(體積比20:1 )中脫去PMB保護(hù)基{ I5]得到醇15 ,產(chǎn)率85%.最后,用Dess-Martin試劑16 ]氧化,以87%的產(chǎn)率得到目標(biāo)產(chǎn)物6-0xodendrolasinolide( 1 ).2實(shí)驗(yàn)部分2.1儀器與試劑Nicolet NEXUS 670及Nicolet AVATAR 360傅里葉變換紅外光譜儀; HP-5988及ZAB-HS型質(zhì)譜儀; Bruker Daltonics APEX I 47e高分辨質(zhì)譜儀; Mercury Plus-300 MHz型核磁共振儀(以CDCl3為溶劑,TMS為內(nèi)標(biāo)).柱層析色譜用硅膠C(煙臺(tái)海洋化工廠);所用無水溶劑均嚴(yán)格按照標(biāo)準(zhǔn)方法處理,使用前蒸出.香葉醇、異戊烯醇、1 3-丙二硫醇從Aldrich 公司購買.其它試劑均為市售分析純,不經(jīng)純化直接使用.2.2化合 物的合成2.2.1 1-氯{ 2E 6E )-2 6-二甲基-8-四氫吡喃氧基-2 6-辛二烯( 4a )的合成 參考文獻(xiàn)8 ]方法,得無色油狀物4:(產(chǎn)率85% ). IR( film) ,i/cm-' :2902 , 1658 ,1443 ,1274 ,1107 ,860 ,813 ;'H NMR( 300MHz ,CDCI3 ),8:1.67( s ,3H ,CH3 ),1.72(s ,3H ,CH3 ),1.49~1.87( m ,6H ,3CH, ),2.04 ~2.21( m ,4H ,2CH2CH= ),3.47 ~3.54( m,1H , CH20 ),3.85 ~3.92( m,1H , CH20 ),3.98( s ,2H ,CH2Cl) ,3.98 ~4.04( m ,1H , 0CH2CH=),4.20~4.26( m ,1H , OCH2CH=),4.60~4.61( m ,1H ,0CHO) ,5.35( t ,1H ,J=6.6 Hz , CH,CH= ),5.50( t ,1H ,J=6.6 Hz , CH,CH= ); EI-MS ,m/z :237[ M-35]*( 1 ),206( 1 ),85( 100 ),67( 39 ),41( 54 ).2.2.22< 2-甲基-1-丙烯基)-1 3-二噻烷(7 )的合成參考文獻(xiàn)[ 9 ]方法,得淡黃色油狀物7(產(chǎn)率97% ). 'H NMR( 300 MHz , CDCl, ),8:1.73( s ,3H ,C中國煤化工1 ,CH2 ),2.75 ~2.98( m ,4H ,2CH2S),4.86( d ,1H ,J=9.9 Hz ,SCHS ),5.|YHCNMHGCHCH=);"CNMR( 75 MHz ,CDC], ),δ: 18.3 ,24.9 ,25.6 ,30.5( 2C),44.4 ,121.1 ,137.7 ; EI-MS ,m/z : 174( M*,74),99( 100),85(92),67( 13 ).2.2.3 ( 2E 6E)-3-甲基-7-{[ 2( 2-甲基-1-丙烯基)-1 3-二噻烷-2-基]次甲基}2 6-辛二烯基四氫吡喃醚( 8 )的合成參考文獻(xiàn)2 ]方法,得淡黃色油狀物8(產(chǎn)率89% ). IR( film) ,i/cm-' :3363 ,2937 ,1294高等學(xué)?；瘜W(xué)學(xué)報(bào)Vol. 281652 ,1440 ,1381 ,1117 ,1024 ,906 ,869 ,813 ,681 ;'H NMR( 300 MHz , CDCI3 ),δ :1.24~2.02( m ,8H ,4CH2 ),1. 65( s ,3H ,CH3 ),1.67(s ,3H ,CH,),1.74(s ,3H ,CH3 ),1.91( s ,3H ,CH3 ),2. 04 ~2. 16( m ,4H ,2CH2C=),2.72( s ,2H ,S2CCH2),2. 74~2.92( m ,4H ,2CH2S),3.45~3.50( m ,1H ,CH20),3.83 ~3.91( m, 1H , CH20 ),3.96 ~4.03( m, 1H , 0CH,CH= ),4.18 ~4.24( m ,1H ,0CH2CH=),4.60( m ,1H ,0CHO),5.25(t,1H ,J=6.3 Hz ,CH2CH=),5.34(t ,1H ,J=6.3 Hz ,CH,CH=),5.48(s,1H ,S2CCH= );"C NMR( 75 MHz ,CDCI3 ),8:16.3 ,17.7 ,19.2 ,19.5 ,25.4 ,26.3 ,27.5 ,27.7 ,30.6 ,39.2 ,50.5 ,52.9 ,62.2 ,63.6 ,97.7 ,120.6 ,128.1 ,130.2 ,130.7 ,138. 0 ,140.0 ;FAB-MS ,m/z :409.3( M+ ).2.2.4 (6E ,10E)-2 6 ,10-三甲基-12-四氫吡喃氧基-2 6 ,10-十二碳三烯4-酮( 9 )的合成 參考文獻(xiàn)[13]方法,在氬氣氛下,將溶于45mL體積分?jǐn)?shù)95%MeOH的化合物8(1.50g,3.66mmol)加入HgCl.(1.99g,7.32mmol)和CaCO2(3.66g,36.6mmol)的70mL體積分?jǐn)?shù)為95%的MeOH懸濁液中,加熱回流30min.冷至室溫,抽濾,減壓蒸除溶劑,用乙醚(50mLx3)稀釋萃取,合并有機(jī)相,依次用5 mol/L AcNH,溶液、水、飽和食鹽水洗滌, 無水Na2SO4干燥.過濾,減壓蒸除溶劑后,粗產(chǎn)品經(jīng)硅膠柱層析[ V(石油醚)V(乙酸乙酯)=20/1 ]純化, 得淡黃色油狀物9( 1. 10 g,產(chǎn)率94% ). IR( film ), i/em-1 :3367 ,2939 , 1687 , 1620 , 1443 , 1382 , 1118 ,1024 ,906 , 703 ;'H NMR( 300 MHz ,CDCl, ),8:1.49~1.84( m ,6H ,3CH2 ),1.61(s ,3H ,CH,),1. 67(s ,3H ,CH3),1. 87(s ,3H ,CH;),2.13(s ,3H , CH; ),2.07 ~2.21( m,4H ,2CH2C=),3.02( s ,2H ,COCH2 ),3.47 ~3.54( m,1H ,CH20),3.85 ~3.91( m, 1H , CH20 ),4.00 ~4.04( m, 1H , 0CH2CH= ),4.20 ~4.26( m ,1H ,OCH2CH=),4.60~4.61( m,1H ,0CHO),5.24( t ,1H ,J=6.6 Hz , CH2CH=),5.36( t ,1H ,J=6.6 Hz , CH2CH= ),6.10( s , 1H , COCH= );'C NMR( 75 MHz , CDCI, ),8:16.4 ,19.6 ,20.7 ,25.4 ,26.4 ,27.7 ,30.7 ,39.3 ,55.4 ,62.3 ,63.6 ,97.8 ,120.7 ,122.8 ,128.8 ,129.8 ,139.9 ,155. 7 ,199.4 ;FAB-MS ,m/z :321.8[ M+H]*.2.2.5 ( 6E 10E)-2 6 ,10-三甲基-12-四氫吡喃氧基-2 ,6 ,10-+二碳三烯4-醇( 10 )的合成將酮9(0.92 g ,2. 89 mmol )溶于10 mL絕對(duì)甲醇中,于0 C分批加入NaBH(0.17 g ,4.33 mmol ),于室溫?cái)嚢?h.加入10mL水淬滅反應(yīng),用乙醚(30mLx3)萃取,合并有機(jī)相,用飽和食鹽水洗滌,無水Na2SO,干燥.過濾,蒸除溶劑后, 粗產(chǎn)品經(jīng)硅膠柱層析[ V(石油醚)V(乙酸乙酯)= 16/1 ]純化,得淡黃色油狀物10(0. 86 g,產(chǎn)率92% ). IR( film), i/em-' :3448 ,2932 , 1670 ,1444 ,1381 , 1201 ,1117 ,1024 ,905 ,869 ,813 ;'H NMR( 300 MHz , CDCI ),8:1.45 ~1.84( m ,6H ,3CH2 ),1.63( s,3H ,CH, ),1.66( s ,6H ,2CH3),1.70(s ,3H ,CH3 ),2.03 ~2.16( m ,6H ,3CH2C=),3. 46~3.51( m,1H ,CH20),3.85~3.90( m,1H ,CH20),3.95 ~4.01( m ,1H , 0CH2CH=),4.19 ~4.26( m,1H ,OCH2CH=),4.39( dt ,1H J=15.0Hz ,J=6.6 Hz ,CH0H),4.59~4.60( m ,1H ,0CHO ),5.13( d ,1H ,J =9.0 Hz , HOCHCH= ),5.20( t, 1H,J=6.3 Hz , CH,CH= ),5.35( t, 1H,J=6.3 Hz ,CH2CH= );BC NMR( 75 MHz , CDCl,),8:16.1 ,16.3 ,18. 1 ,19.5 ,25.4 ,25.7 ,26.2 ,30.6 ,39.3 ,48.1 ,62.2 ,63.6 ,65.7 ,97.8 , 120.9 , 127.5 , 128.1 , 131.9 , 134.7 , 139.9 ; FAB-MS , m/z :323.4[ M+H ]*.2.2.6 (2E 6E)-9{ 4-甲氧基芐氧基)-3 7 ,11-三甲基-2 6 ,10-十二碳三烯基四氫吡喃醚( 11 )的合成在0 C下,將NaH(0. 29g ,7. 25 mmol ,質(zhì)量分?jǐn)?shù)60% )分批加入溶于20 mL無水DMF的醇10( 0.78g,2.42mmol)中,攪拌1h后將溶于2.5mL無水DMF的對(duì)甲氧基芐溴(0.97g,4.83mmol)和催化量的TBAI逐滴加入到反應(yīng)體系中,0 C下繼續(xù)攪拌1 h后升至室溫.攪拌反應(yīng)12 h.用飽和食鹽水( 10mL )小心淬滅反應(yīng),用乙醚( 30 mL x3 )萃取, 合并有機(jī)中國煤化工濾,蒸除溶劑后，粗產(chǎn)品經(jīng)硅膠柱層梳[ (石油醚)U(乙酸乙酯)= 30/1 ]純化HCNMH G86g ,產(chǎn)率87% ). IR( film) ,i/cm-' :2934 ,1670 ,1513 ,1445 ,1247 ,1115 ,1030 ,905 ,817 ;'H NMR( 300 MHz , CDCI; ),δ:1.49~1.86( m ,6H ,3CH2 ),1.56( s ,3H ,CH3 ),1.60( s ,3H ,CH3 ),1. 68( s ,3H ,CH3 ),1.75( s ,3H ,CH3),2.02 ~2. 37( m ,6H ,3CH2C= ),3.47 ~3.54( m,1H ,CH20),3. 79( s ,3H , ArOCH, ),3.86~3.92( m,1H ,CH2O ),3.98 ~4. 05( m ,1H , 0CH,CH=),4.12( dt ,1H ,J=15.6 Hz ,J=6.9No.7李毅等:6-Oxodendrolasinolide的全合成1295Hz , CH0Ar),4.21 ~4. 27( m ,2H ,0CH2CH= ,ArCH2 ),4.48(d,1H ,J=11.7 Hz ,ArCH2),4.61 ~4.62(m,1H,0CHO),5.07(d,1H，J=9.0Hz,ArOCHCH=),5.15(t，1H，J=6.0HzCH2CH=),5.35(t ,1H ,J=6.6 Hz ,CH2CH=),6.85( d ,2H ,J=8.4 Hz ,ArH),7.23( d ,2H ,J=8.4 Hz ,ArH);BC NMR( 75 MHz , CDCI3 ),8:16.4 ,16.6,18.3 , 19.6 ,25.4 ,25.8 ,26.4 ,30.7 ,39.5 ,45.8 ,55.2 ,62.2 , 63.6 , 69.1 ,73.7 ,97.8 , 113.5 , 120.4 , 126.4 , 129.1 , 131.2，131.9 ,135.3 ,140.3 ,158.8 ;FAB-MS ,m/z :441.8( M* ).2.2.7 ( 2E 6E )-9{ 4-甲氧基芐氧基)-3 ,7 ,11-三甲基-2 6 ,10-+二碳三烯-1~醇( 12 )的合成參考文獻(xiàn)14 ]方法合成,得淡黃色油狀物12(產(chǎn)率91% ). IR( film ),i/cm-1 :3396 ,2928 , 1612 ,1513 ,1445 ,1247 ,1174 ,1037 ,822 ,754 ;'H NMR( 300 MHz , CDCl3),δ :1.56(s ,3H ,CH3 ),1. 60(s ,3H ,CH3),1.67(s ,3H ,CH3 ),1.75(s,3H ,CH3 ),2.03 ~2. 37( m,6H , 3CH2C= ),3.80( s ,3H ,ArOCH, ),4. 09~4.17( m ,3H , CH2OH , CHOAr),4.25( d ,1H ,J=8.7 Hz ,ArCH2 ),4.48( d,1H，J=8.7 Hz ,ArCH2 ),5.08( d ,1H ,J=9.3 Hz , ArOCHCH=),5.14( t ,1H J=6.3 Hz ,CH2CH= ),5.40(t ,1H ,J=6.3 Hz , CH,CH=),6.86( d ,2H ,J=8.7 Hz , ArH),7.23( d ,2H ,J=8.7 Hz ,ArH);'C NMR( 75 MHz ,CDCI3),8:16.2 ,16.5 ,18.3 ,25.8 ,26.3 ,39.3 ,45.8 ,55.2 ,59.3 ,69.0 ,73.5 ,113.5 ,123.3 ,126.3 ,129.2 ,131.1 ,132.0 ,135.4 ,139.6 ,158. 8 ;FAB-MS ,m/z :359.5[ M+H ]*.2.2.8 (2E 6E)-9( 4-甲氧基芐氧基)-3 ,7 ,11-三甲基-2 ,6 ,10-十二碳三烯醛( 13 )的合成 將醇12(0.30g ,0. 82 mmol )溶于8 mL正己烷中,加入MnO2(0.93g ,10.7 mmol ),于室溫?cái)嚢璺磻?yīng)20h.過濾,濾液經(jīng)減壓濃縮, 粗產(chǎn)品經(jīng)硅膠柱層楓[ K( 石油醚)V(乙醚)=8/1 ]純化, 得無色油狀物13( 0. 25g,產(chǎn)率84%).IR(film),i/cm-1:2930,1673,1612,1513,1445,1247，1177,1072,1037,822,754 ; ' H NMR( 300 MHz , CDCI3),8:1.57(s ,3H ,CH,),1.61(s ,3H ,CH3 ),1.75( s ,3H ,CH3),2. 16( s ,3H ,CH, ),2.03 ~2.37( m ,6H ,3CH2C= ),3.79( s ,3H , ArOCH, ),4.12( dt ,1H ,J=6.9Hz ,J=2.7 Hz , CH0Ar),4.25( d,1H ,J=8.7 Hz, ArCH2 ),4.48( d , 1H,J=8.7 Hz , ArCH2 ),5. 05 ~5.12( m ,2H , ArOCHCH= ,CH2CH=),5.88( d ,1H ,J=8.1 Hz ,CH=CH0),6.85( d ,2H ,J=8.4 Hz ,ArH),7.22( d ,2H ,J=8.7 Hz ,ArH),9.98( d,1H ,J=8.1 Hz , CHO );BC NMR( 75MHz , CDCl, ),8: 16.6, 17.6 ,18.3 ,25.7 ,25.8 ,40.4 ,45.8 ,55.2 ,69.1 , 73.4 ,113.5 , 124.9 ,126.3 ,127.3 ,129.1 ,131.1 ,133.3 ,135.5 ,158.9 ,163.9 ,191.3 ;FAB-MS ,m/z :357.4[ M+H]*.2.2.9 4[( E )-6( 4-甲氧基芐氧基)4 8-二甲基-3 7-癸二烯基]}5H-呋喃-2-酮( 14 )的合成 參考文獻(xiàn)[ 6 ]方法合成,得淡黃色油狀物14(產(chǎn)率47% ). IR( film),i/cm-' :3396 ,2929 , 1779 ,1749 , 1638 ,1513 ,1444 ,1380 ,1247 ,1173 ,1036 , 887 ,823 ,754 ;'H NMR( 300 MHz , CDCI3 ),8:1.58( s ,3H ,CH3),1.61(s ,3H ,CH3 ),1.76(s ,3H ,CH3 ),2.00 ~2.45( m,6H ,3CH2C= ),3.80( s ,3H ,CH3OAr),4.14( dt ,1H ,J=9.6 Hz ,J=7.2 Hz , CHOAr ),4.24(d ,1H ,J=8.7 Hz ,ArCH2 ),4.48(d,1H,J=8.7Hz,ArCH2),4.70(s,2H,OCH2C=),5.06~5.11(m,2H,ArOCHCHCH2CH=),5.83(s ,1H , COCH =),6.85( d ,2H ,J =8.7 Hz, ArH ),7.22( d ,2H ,J =8.7 Hz ,ArH );'C NMR( 75 MHz ,CDCI, ),δ :16.6 ,18.3 ,25.7 ,25.8 ,28.5 ,30.3 ,45.8 ,55.2 ,69. 1 ,73.1，113.6 ,115.5 ,124.3 ,126.1 ,129.2 ,131.0 ,134.3 ,135.7 ,158.9 ,170.3 ;FAB-MS ,m/z :371.2[ M +2.2.104[( E)-6-羥基)4 8-二甲基-3 ,7-癸二烯 基]-5H-呋喃-2-酮( 15 )的合成參考文獻(xiàn)[ 15 ]方法合成,得淡黃色油狀物15(產(chǎn)率85% ). IR( film ), i/cm-' .24132926 1780 , 1746 , 1638 , 1443 ,中國煤化工1381 ,1172 ,1039 ,891 ,710 ;'H NMR( 300 MHz ,CDCI,,1.62(s ,3H ,CH3),1.70(s ,3H ,CH3),2. 15~2.51( m ,6H ,3CH2C=),4THCNMHG,J=8.1Hz ,CHOH),4.74( s ,2H , 0CH2C=),5.12 ~5.23( m , 2H , HOCHCH= , CH2CH=),5.86( s ,1H , COCH= ),6.85( d ,2H ,J=8.7 Hz ,ArH),7.22( d ,2H ,J=8.7 Hz ,ArH );'C NMR( 75 MHz ,CDCI3 ),8:16.3 ,18.1 ,28.5 ,29.8 ,47.8 ,66.1 ,73.1 ,115.6 ,125.4 ,127.4 ,134.2 ,135.2 ,139.7 ,170.0 ; FAB-MS ,m/z :249.8(M+ ). .1296高等學(xué)?；瘜W(xué)學(xué)報(bào)Vol. 28.2.2.116-0xodendrolasinolidd( 1 )的合成將醇 15( 44 mg ,0. 18 mmol )溶于2 mL. 無水CH2Cl2中,加入Dess-Martin試劑( 112 mg ,0. 26 mmol) ,室溫下攪拌2 h.用1 mL飽和NaHCO,溶液淬滅反應(yīng),用乙醚( 10 mLx3 )萃取,合并有機(jī)相,依次用水、飽和食鹽水洗滌, 無水Na2SO,干燥.過濾,蒸除溶劑后,粗產(chǎn)品經(jīng)硅膠柱層楓[ V(石油醚)U乙酸乙酯)=6/1 ]純化,得淡黃色油狀物1( 39 mg ,產(chǎn)率87% ).IR( film),i/cm-1 :1778 ,1747 ,1684 ,1618 ,1442 ,1127 ,1034 ,886 ;'H NMR( 300 MHz , CDCl3 ),δ:1.65( s ,3H ,CH3),1.88( s ,3H ,CH3 ),2. 14(s ,3H ,CH3),2.37( m ,2H ,CH2CH=),2.49( t ,2H ,J=6.6 Hz ,CH2C=),3.06(s ,2H ,COCH2C=),4.74(s ,2H ,0CH2,C=),5.20(t ,1H ,J=6.6 Hz ,CH2CH=),5.85(s ,1H ,C0CH=),6.06(s ,1H , C0CH=);'C NMR( 75 MHz ,CDCl3 ),δ :16.7( C4),20.7( C10 ,C11 ),25.7( C9 ),27.7( C2),28.4( C1 ),54.9( C5),73.1( C4' ),115.7( C2' ),117.4( C3 ),122.8( C4 ),126.4( C7 ),132.2( C8),156.5( C3'),169.8( C1'),198.5( C-6 ); FAB-MS ,m/z :249.兀M+H]° ;HRMS( ESI ),計(jì)算值:266. 1751[ M +NH4]° ,實(shí)驗(yàn)值:266. 175 8.參考文南[ 1 ] SchneiderJ. A. ,LeeJ. ，Naya Y. ,et al.. Phytochemistr[ J], 1984 ,23(4 ):759- -764[ 2 ] ZhangT. ,LiY. ,PengL. Z. ,et al. Chinese Chemical Lett.[ J],2004 ,15(2):141-142[ 3 ] QuJ. ,Liw. D. ,LiJ. ,el al.. Chinese Chemical Ltt.[J],1997 ,8(5):411-412. [ 4] QuJ. ,Li W. D. ,LiJ ,et al.. Chinese Chemical Lett.[J],1996 ,7(4) :303- -304[ 5 ] GarbaccioR. M. , Stachel S. J. , BaeschlinD. K. ,etal.. J. Am. Chem. Soe.[J],2001 , 123( 44 ): 10903- -10908[ 6 ] Corey E. J. ,Schmidt G. . Tetrahedron Lett.[J], 1980 ,21( 8):731-734[ 7 ] Camps F. , ParenteC. A.. Synthesi;[ J],1978 ,(3):215- -216[ 8 ] BoseA. K. ,Lal B.. Tetrahedron Lt.[ J],1973 ,( 40) :3937- -3940[ 9 ] Seebach D. ,Corey E. J.. J. Org. Chem.[J],1975 ,40(2):231- -237[10] Murphy W. S. , WattanasinS.. J. Chem. Soc. Perkin I[J] ,1980 ,( 12 ):2678- -2682[11] PearsonR. G. ,SongtadJ.. J. Am. Chem. Soc.[ J], 1967 ,898 ):1827-1836[12] LiJ ,LanJ. ,LiuZ. ,etal.. J Nat. Prod.[J],1998 ,61( 1 ):92- -95[ 13] CoreyE. J. , CrouseD.. J. Org. Chem.[J],1968 ,3( 1 ):298- -300[ 14] Miyashita N. , Yoshikoshi A. , GriecoP. A.. J. Org. Chem.[ J],1977 ,42( 23 ):3772- -3774[15] Oikawa Y. , Yoshioka T. , Yonemitsu 0.. Tetrahedron Lett.[J],1982 ,23(8 ):885- -88[16] DessB. D. ,MartinJ. C.. J. Org. Chem.[ J],1983 ,48( 22 ):4155- -4156Total Synthesis of 6-OxodendrolasinolideLI Yi' , ZHANG Tao2 ,LI Yu-Lin'( 1. State Key Laboratory of Applied Organic Chemistry , Instiute of Organic Chemistry , Lanzhou University,Lanzhou 730000 , China ;2. Minsheng Group Shaoxing Pharmaceutical Co. Ltd. , Shaoxing 312071 , China )Abstract An fficient total synthesis of 6-oxodendrolasinolide( 1 ) ,a new farnesane-type sesquiterpene lac-tone , was described. The synthetic route was completed from geraniol 2 and 3-methylbut-2-en-1-ol( 5 )through twelve steps in 5. 6% overall yield. The key steps were regioselective alkylation of the anion of vi-nyldithian 7 with allylic chloride 4a to generate compound 8 , followed by hydrolyzation of the dithiane to affordcompound 9. The reduction of enone 9 gave alcohol 10 , wl中國煤化rnethoybenzyether 11.Subsequently , tetrahydropyranyl protective group was removTYHc N MH G key intermediate ade-hyde 13. Then after Corey's oxidative lactionization reaction tollowed by deprotecton of the PMB group com-pound 15 was formed , which underwent Dess-Martin oxidation to afford the title compound 1.Keywords Total synthesis ; Butenolide ; Sesquiterpene ; Regioselectivity alkylation(Ed.:HJ,Z)