Chapter06有-機(jī)-合-成-設(shè)-計(jì)-概-論

/

μúáù??óD?úo?3ééè??????

Synthesismustalwaysbecarriedoutbyplan,andthesyntheticfrontierscanbedefinedonlyintermofthedegreetowhichtherealisticplanningispossibleutilizingalloftheintellectualandphysicaltoolsavailable.

R.B.Woodward,1956

óD?úo?3éê?óD?ú?ˉ?§?Dò???1?à?μ?·??§￡?ò2ê?ò???ê?·?????μ?áìóò￡?óD?ú?ˉ?§?ò?aá??ù′?àí??oíó|ó??D??μ?Dèòa￡?2???′óê?×?ò??a?ò?′?a?á11óD?ú·?×óμ?o?3é￡???ìì???ü3??aóD?ú·?×ó1¤3ì?§?￡??1üμ±??ò??a?ˉo???êyá?ò?3?1y2000íò??￡????Dó?′ó?à?aóD?ú?ˉo???￡?óD?ú?ˉ?§?òè?è??y??′óê?×?D?μ??ˉo???μ?o?3éò??ú??μ??ü?à?÷??àí?ˉ?￠éúàíD??êμ??ˉo????￡óD?úo?3éê?ò???êμ?é???§￡?μ?ê??ú?a?1o?3é1¤×÷???°￡?óè??ê????′?óóD?ú·?×óμ?o?3é￡?±?D?òaóDò???o?àíμ?????￡??a?íê?o?3ééè??1¤×÷￡??üê?óD?úo?3éμ?áé?ê?￡3¤?úò?à′óD?úo?3é±?ót?a???§?Dμ?ò?ê?￡???1üμ±ê±óD?ú?ˉ?§μ?Dí?à·?????ò???è?á????-?μí3í?àíμ??×??￡?μ?ê??üê??à?êà′?a???é??ò?óD?ù±??ˉ￡?o?3ééè??μ?3é1|êμ?ùê1óD?úo?3é?y?e2?′óò?ê?×??ò???§￡?2?éùר??μ?1?μ?ò2?¤?÷á??aò?μ?1-5?￡

óéCorey4ìá3?2￠óé′?·￠?1?eà′μ?“o?3é?a”(Synthon)?￠“·′o?3é·???”(RetrosynthesisorAntisynthesis)?￠“·′o?3é?a”(Retron)μ?????ê?μ±??óD?úo?3é?D×??a??±é?óêüμ?éè??·?·¨???￡Coreyμ?·′o?3é·???±?óD?úo?3é?ˉ?§??3?×÷ê?Harvard?§?éμ?′ú±í￡?ó?Cambridge?§?éμ?éú?′o?3é?§?μò??e×é3éá???′úóD?úo?3ééè??????μ??ù×ù?￡?aò????°ò????t?????í′óCoreyμ??aD??ù±?????3?·￠￡???óD?úo?3ééè??μ?·?·¨×÷ò???à¨D?μ??ééü?￡

6.1óD?úo?3éμ?èy??3?·￠μ?

óD?ú?ˉ?§o?3éêμ?éêò′óê?μ??D??￡???3?·￠μ?2?íao???áDèy??￡o??D?·￠??μ??òóDè¤μ?·′ó|1á31óúóDòaò?μ?o?3é1¤×÷?D￡?à?ó?ììè????òéú2ú?D?′3?·?à?ó?μ??-á?à′o?3éóD???μμ?2ú?·￡?ò??°o?3éòò?3??Dèòa??ìá3?μ?ì??¨??±ê·?×ó?￡

6.1.1à?ó?D?·′ó|

ò?D?·′ó|?úàí?òo?3é·?·¨?§μ??D????·￠??á?ò?D?D?μ?óDè¤μ?·′ó|￡??aê±?í×?è???è?μ???μ?è?o?ó|ó??aD?·′ó|óúóDòaò?μ???±ê·?×óμ?o?3é?Dè￥?￡è?°?ê??ê′úò?à′????μ?Sharpless·′ó|￡?ê?óéSharplessD?×é?ú?à?ê?D???·???ˉ·′ó|?D·￠??μ?(1980)6?￡·￠??oóμ±?′×a?òè?o?ó|ó??aò?·′ó|óú1a??D?ììè?2ú??μ?o?3é???D￡?è??1?ú???￠°×èy??ò??°à￥3?D??￠??μè7￡?Kendeμè???aò?·′ó|ó|ó??ú1a?§??D?Aklavinoneμ?o?3é?D8?￡???úSharpless?·???ˉò?3é?aóD?úo?3é?ˉ?§?ò1¤?????D×?3￡ó?μ?o?3é1¤????ò??￡

?a?1á?μè?ú°×èy??o?3é?D·￠????áD?????ù?ˉ·′ó|????D???o?￡??????íéè??á?à?ó?′?·′ó|à′o?3é??×ó2ú??μ?μ?D??￠??9?￡

??ò???μè10·￠??ééylideo?3é12é?μ?è?￡?ía￡??￡°·ì??t??oí￡?2ú?êo?￡?????ò2?íéè??o?3éá?ò?D??à??Díììè?2ú??￡?è?￡o

?????×μè11·￠??ò???óDD§o?3é???·[3,3,1]èé￡-9￡-íaì??μμ?D?·?·¨￡???Dí?àììè?2ú??￡?è?êˉé???(Huperzine)μè?ío?óD?aò?àà1??ü￡?òò′??ééè??à?ó??aò?·′ó|ò?o?3é?aò?ààììè?2ú???°??àà?????￡?aò?·?·¨oó?a?à1ú?ˉ?§?ò?ù2éó?122￠êμ?ùóúHuperzineAμ?o?3é?D?￡

Overmanμè13·￠??2-???ù-1,2-?t′?ì??μ?ú?á′??ú??ó?è?·￠éú??o?·′ó|ê±?á·￠éú??????à??·￡?·′ó|??óDoüo?μ?á￠ì?????D??￡óé′?￡?????éè??o?3éá?ò??μáDììè?2ú???￡

?ò??′ó?aD?ày×ó?D?éò?·￠???a?ù3?·￠μ?o?3ééè??￡?1??ü?úóúè?o????aààD?·′ó|×é?ˉμ?ò???o?3é?·??μ?1??ü2??è?Dè￥?￡

6.1.2à?ó??-á?μ?o?3é

?3D?à′?′·á??μ?ììè?×ê?′?òéú2ú?D?′±?à?ó?μ??±2ú???￠±???á?3￡??óD?úo?3é?ˉ?§?òìá3?oüóDòaò?μ??D????ìa￡??′è?o?à?ó??ü??×÷?a?-á?o?3é3??ü?????μμ?2ú?·￡????°?aD?1¤×÷±??éè?×ê?′?ˉ?§μ??D??·??§?￡è?￡-pineneê??ò1ú?é?úóí?Dμ??÷òa3é·?￡?è?o?à?ó?ò?o?3é??è?·??á′?￡?áú????ààμ???á??ò?è±￡á??·???·?ù??ò?2?à?ó?￡??aò??-3é?aò?D?o?3é??ìa×éμ??D????ìa?￡

μ?ó??é?úóí12í?2úéúμ??é??(?÷òa3é·??é???áabieticacid)3yò?D?μí??ó?í?ía￡??1?′μ?μ?oüo?μ?à?ó?￡?àà??μ??é???1óD?é°???(cembrene)μè?￡

?àY?μ?éú3¤±é2?è??ò￡??ù???ù?a3y?ò1ú??·?êyê??ù2úμ??2??o????à?àY???ía￡????üμ????ù2ú?÷òao??àY??á￡?òò???àY??áμ?à?ó?ò2?í3é?aò?D?o?3é1¤×÷??￡?ì?±eê??ò1ú???§?òμ??D????ìa14?￡

???üμ?ììè?×ê?′￡?è?ì??D×?á???μ???ì?ì?ò??±ò2ê??μ·±±?ê1ó?óúo?3é?D??μ?3?·￠?-á?￡?àyè?ó?óú°×èy??A4μ?o?3é15?￡

°±?ù?á?D×?á???μ?ê?L-1è°±?á(L-GlutamicAcid),?üμ?à?ó?ò2ê?o?3ééè???-3￡????μ?ê?D??-á?16?￡￡¨2???G.M.Coppolaetal.?°AsymmetricSynthesis?±p.216,JohnWiley&SonsNY1987.)

ò??-á??a3?·￠μ?μ?o?3ééè??￡?1??ü?úóúè?o?3?·?à?ó??aò??-á?μ??á11ì??÷oí?ˉ?§·′ó|ì?D??￡

6.1.3ì??¨??±ê·?×óμ?o?3é

?aê??úóD?úo?3ééè??ê±×??-3￡ó?μ?μ???ìa￡??ò?????ú????μ??úèY?D?í?a??òéìa??DDé?è?μ?ì????￡áíía￡?è??ò??×D????2ìò?é??tàào?3ééè??ê±?éò??′μ?￡?3?·￠μ?èy????óD2?í?￡?μ?×????1ê?òa1é?áμ?ò???ì??¨μ???±ê·?×ó￡?òò′???±ê·?×ó?a3?·￠μ?μ?o?3ééè???-?ò?úèyààéè???D??ê?Dèòa2???μ??￡

6.2o?3ééè??μ?èy2??ú

??????ò???ì??¨??±ê·?×óμ?o?3é￡?μúò?2?ê????a??·?×óμ??á11ì??÷oíò??aμ?àí?ˉD??ê??DDê??ˉoí??2ì￡?óé′??éò??ò?ˉo?3é?Dμ??êìa?ò??±ü?a2?±?òaμ?í??·?￡??è????è??μ?o?3é￡??a30??ì?μ?èyY?·?×óê?ò????DD???3?μ??ˉo???￡??í?éò?éè??ò?ì??·??￡?′ó?D??3?·￠?t±???3?μ?í?ê±??DDo?3é￡????????°áD?ù??E2μ?o?3éê±￡?óéóúò??a·?×ó?D￡-???ùíaì??μê?oü2??è?¨μ?￡?òò′??í?éò?°2???úo?3é?·??μ?×?oó??2?ê±?ùD?3é?aò??á11μ￥?a￡?ê1??±ü?a?-àú???àμ??ˉ?§·′ó|?￡

μú?t2?ê?ò?é?ê?·????a?ù′?￡?????ò?2?ò?2?μ1í?3?o?3é′???±ê?ˉo???μ??÷???·??oí?é?üμ?ò×μ??eê??-á?￡??aò2?íê??ù??·′o?3é(RetrosynthesisorAntisynthesis),′?·??????·ó????yμ?o?3é?yo??à·′?￡o?3é?D??ê1ó??÷???÷?ùμ?·′ó|à′D?3é·?×óμ?1??ü￡???±?·?×ó1??üé?μ?1ù?üí?￡?′ó??×?????μ???±ê·?×ó￡??ú·′o?3é?D?òê?à?ó?ò??μáD?ù??μ??°×a?ˉ(Transformation)?±à′í?μ?3?ò??μáD?D??ì?oío?êêμ??eê??-á??￡×a?ˉó??????yí·±íê?()ò?ê?óD±eóúμ￥???yí·±íê?μ?·′ó|()?￡óé?àó|μ?ò??a?ò?é??μ?·′ó|????DD×a?ˉ?ùμ?μ??á11μ￥?a3????a?°o?3é?a(Synthon)?±￡?óéo?3é?a?ù?éò?í?μ?(ó?Dé??±íê?)μ??àó|μ?ê??á?ò?D??ì?￡?óDê±o?3é?a±?éí?′ê?ê??á?ò?D??ì??￡

??óú???°???×é?o?3é?aó?o?3é?D??ì?μ??ì?yê1ó?￡?Corey?ú·′o?3é×a?ˉ·???ó?ìá3?á?ò???ê?ó?￡??′·′o?3é?a(Retron)17,18?￡·′o?3é?aòa?a??DD?3ò?×a?ˉ?ù±?òaμ??á11μ￥?a?￡è???áD?á11μ￥?aA,B,C,D·?±e?aDiels-Alder·′ó|?￠Claisen?????￠Robinson?ì?·?￠Mannich×a?ˉμ??ù±?·′o?3é?a?￡

óDê±??±ê·?×ó?D??°üo?2?·?·′o?3é?a￡?è???áDE,F,G?′o?óDRobinson?ì?·μ?2?·?·′o?3é?a￡??ü??í¨1yè??é×a?ˉ?í?éò?μ?μ?íê??μ?·′o?3é?a?￡

·′o?3é·???μ?o?D??êìaê?×a?ˉ￡?·′o?3é?aoío?3é?a?òê??aò??êìaμ?á???·???￡o?°??ê?×a?ˉμ?±?òa?á11μ￥?a￡?oó??ê?×a?ˉ??μ?μ?μ??á11μ￥?a?￡×a?ˉí??ùóDá?′óààDí￡??′ì?ì??üμ?×a?ˉoí1ù?üí?μ?×a?ˉ?￡??±ê·?×óì?-ì?1??üμ?×a?ˉ°ü਷?2e(Disconnection)￡?áa?ó(Connection)oí????(Rearrangement)èy???￡

ì?￡-ì??ü·?2eμ?μ?o?3é?a?éò?óD￡o

1?￡?óêüμ?×óμ?(a)o?3é?a

2?￡??μ?×óμ?(d)o?3é?a

3?￡×?óé?ù(r)o?3é?a

4?￡??μ?×ó?DD?μ?(e)o?3é?a

????μ?±í?D?ò???éò?′óò?D?êμày?′3?·?2eμ??é??￡o

áa?óoí?????a?tàà×a?ˉí¨3￡?ú?????yí·é??ó×￠￡??aê±μ?o?3é?aí¨3￡?′?aê??á￡??D??ì?￡??TDè??ò?2?í?μ?￡?è???±íμ?ày×ó￡o

??±ê·?×ó?D1ù?üí?μ?·′o?3é×a?ˉò2?óo?3é·′ó|?Dò??ùóDèy??ààDí￡o±???(Interconversion)(FGI),òyè?(Addition)(FGA)oí??3y(Removal)(FGR)?￡

???′?ò??ì?ê1ó?é?ê??÷×a?ˉ1y3ìò2?í?éò?í?μ?3?o?3é??±ê·?×ó?ùDèμ?ò×μ?μ??-á?￡?è?￡o

???òμ￥μ???±ê·?×ó?-??2?×a?ˉ?í?éò?μ?μ?o?3éμ??eê??-á?￡?μ????′?óμ???±ê·?×ó?ò?íDèòa3¤μ??àμ?×a?ˉ￡?è?2???×??′?óμ???éú??Aμ?·′o?3é￡?????ê?ò???o?3éμ?í???￡?í??D?a?ò?ˉ?e??￡?2?D′3?o?3é?a￡????±?óD′3??àó|óú??o?3é?aμ??D??ì??òê??á?￡

?1Dèòa??3?μ?ê?￡?3yá?×??òμ￥μ???±êò?ía￡????áóD2??1ò?ì?μ?·′o?3é?·??￡?·?×óóú?′?ó?a???é?üμ?·′o?3é?·???í???à￡??Toìá?3?D?D??￠??ê?ò???ê?áù??ì??-×ó?±á′′?μ?òò?á?￥￡??á112￠2????′?ó￡?μ???·′o?3éμ??é?üí????òoü?à?￡????μ?±íê??ù?Yò?±¨μà3é1|o?3éμ??·??19,20￡????-3?μ?·′o?3éí???,￡?í?±í?D??±í?÷ì?1??üμ?·?2e×a?ˉoí×?oóí?μ?3?μ?ê??á?-á?￡?àà???a?ùí?μ?3?μ?í??óè??ò??3¤μ?ê÷￡??ùò?ò23?o?3éê÷?￡êμ?ê1¤×÷?D2??é?ü????ò?ì??·????è￥êμ?éêòêμ?ù￡??ùò??1±?Dè??o?3éê÷??DDDT??￡?ò2?íê?±?D???2ì?￠±è??2￠??DDè?éá?￡

?Toìá?3?D?D??￠??o?3éê÷

μúèy2?ê?′óo?3é·??ò??DD?ì2é￡?ò2?íê???o?3éê÷μ???2?￡?è?éá?￡óD?úo?3éμ?1¤×÷?úèY?????????éò??μóDèy??è???￡oì?1??üμ??¨á￠￡?1ù?üí?μ?????￡?ò??°è·á￠?yè·μ?á￠ì??ˉ?§?￡?°?tè????úé?ò?2?éè???Dò??-ìá?°￡????úμ??aò?2??ò×???òa??2ìá￠ì??ˉ?§μ??êìa?￡è??·?Tóüê÷?×3?μ??ˉo?D??￠??-multistriatinóD????ê?D??DD?￡?è???°′??ê??ùê?μ?·′o?3ééè????μ?μ?o?3é?·??￡?×?oó???áμ?μ?á￠ì?òì11ì?μ??ìo????￡

óéóú???D??óD￡-òì11ì??üòyó??×3?￡??ùò?±?D?????áíía?ü????á￠ì??ˉ?§μ?·′o?3é×a?ˉ￡??aD?±è??D?μ??????ò?????úoó??ìá?°?￡

3yá￠ì??ˉ?§?êìaía￡???è?o?3éμ??-??D??êìa￡?°üà¨?·??3¤?ì￡?2ú?ê￡??-á?ò×μ?D?￡?·?à?·?·¨μè??±?D??óò???2ì?￡?a?ù2??üé???3?×???μ?o?3ééè???￡

±???2??????×

a)Warren,S."DesigningOrganicSynthesis",Chichester,Wiley,1978;b)Warren,S."OrganicSynthesis,TheDisconnectionApproach",Chichester,Wiley,1982.

a)Fuhrhop,J.andPenzlin,G.OrganicSynthesis,VCH,NewYork,1983;b)Fuhrhop,J.andPenzlin,G.OrganicSynthesis,2ndEd.,VCH,NewYork,1994.

Hendrickson,J.B."GeneralProtocolforSystematicSynthesisDesign",TopicsinCurrentChemistry,1976,62,49.

Corey,E.J."GeneralMethodsfortheConstructionComplexMolecules",Pure&Appl.Chem.1967,14,19.

Turner,S."TheDesignofOrganicSyntheses"AmsterdamElsevier,1976.

Katsuki,T.,Sharpless,K.B.J.Am.Chem.Soc.1980,102,5974.

Rossiter,B.E,Sharpless,K.B.J.Am.Chem.Soc.1981,103,464.

Kende,A.S.,Rizzi,J.P.J.Am.Chem.Soc.1981,103,4247.

Wu,W.-L.,Wu,Y.-L.TetrahedronLett.