TOTAL SYNTHESIS OF ∆ 12-PROSTAGLANDIN J3, A HIGHLY POTENT ANT SELECTIVE ANTILEUKEMIC AGENT K. C. Nicolaou,* Philipp Heretsch, Abdelatif ElMarrouni, Christopher R. H. Hale, Kiran K. Pulukuri, Avinash K. Kudva, Vivek Narayan, and K. Sandeep Prabhu

Introduction Retrosynthesis of the nature product Procedure of synthesis conclusion

Introduction -natural product ∆12-Prostaglandin J3 Structure Property term Name ∆12-PGJ3 (1) Isolated from Isolated by Biological actitivity Selective Antileukemic Agent 20碳的天然物，由魚油omega-3 fatty acid得來 Prostagladin 若以cyclopentenone 為中心的話，在alfa的位置linking一條7碳的長鏈，在beta position linking hexanoic acid Prostagladin 具有2個chiral center 分別為C8 和 C15，而在C15 position 是一個具有立體位像的hydroxyl group

Introduction -Pathway for the formation of the A3/J3-IsoPs by the nonenzymatic peroxidation of EPA Prostaglandin是由 omega-3 fatty acid 來，如圖所示，omega-3 fatty acid transform to prostagladin 是一個一連串 free radical reaction，free radical 容易在allic position react , so C7、C10、C13、C16產生了四種不一樣的途徑，而偏合成的prostagladin J3 由作用在C13的分支上延伸出來的產物

Introduction -relative natural product 所以我們就來細講prostagladin J3的由來及反應機制，首先起使物為omega-3二十碳鏈的fatty acid在 radical 的作用後，在alliyl position上產生出radical，經過racdical rearragement後，在C11 position 與氧鍵結，產生出peroxide racdical，而後peroxide radical 與C8-C9的DOUBLE boud 及C12 DOUBLE bind 做intramolecular cyclization，最後裂解氧化，進而形成PGE3及PGD3，而PGE3及PGD3脫水後，就可以分別形成產物PGA3及PGJ3，所以PG的意思為prostagladin，而有E、D、A、J四種構型，最後3個意思為在支鏈上具有多少個double，依據此歸類，即可得知命名

Introduction -relative natural product 所以類似天然物有這些，而本篇所要合成得天然物可能是由PGJ3轉變而來

Introduction -Total synthesis of ∆12-PGJ2, 15-deoxy-∆12,14-PGJ2, and related compounds (Yuichi Kobayashi) Kobayashi團隊是利用已具有立體位向得acetyl group作為trost reaction，而後aldol reaction 在alfa碳上接上支鏈形成天然物的架構 Tetrahedron Letters. 2004, 45, 1199 –1202

Introduction Retrosynthesis of the nature product Procedure of synthesis conclusion

Retrosynthesis of ∆12-PGJ3

Introduction Retrosynthesis of the nature product Procedure of synthesis conclusion

Procedure of synthesis -Synthesis of the fragement 2 η2 π-allyl complex Malonate dirhodium tetracaprolactamate WEINREB魏因勒卜

Procedure of synthesis - Synthesis of the fragement 3 pyridinium tribromide

Procedure of synthesis -Total synthesis of the nature product sodium chlorite (NaClO2) under mild acidic conditions(pinnick oxidation) 猜測:使用KMnO4可能會導致裂解，使用CrO3 可能會在allylic position接上Hydroxyl group and oxidation TMSCH2N2:Trimethylsilyldiazomethane

Introduction Retrosynthesis of the nature product Procedure of synthesis conclusion

CONCLUSION The asymmetric total synthesis of nature product ∆12-PGJ3 by using asymmetric Tsuji-Trost reaction and asymmetric Mukaiyama aldol reaction. the yield of the ∆12-PGJ3 is 5% (14step)

CONCLUSION

REFERENCE Angew. Chem. Int. Ed. 2014, 53, 10443 –10447 Tetrahedron Letters. 2004, 45, 1199–1202 Chem. Rev. 1996, 96, 395-422

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