天然有机合成方法(研究生用).ppt

Total Synthesis of Taxol Palytoxin (海葵毒素） Y. Kishi@Harvard 其他代表性海洋毒素 Maitotoxin（刺尾鱼毒素） Maitotoxin 97 stereocenter LD50 = 50 ng Molecular formula C164H256O68S2Na2 Molar mass 3422 g/mol 糖的合成I （光合作用） 糖的合成II （Emil Fisher合成，1891年） 糖的合成III （Sharpless合成，1983年） 糖的合成IV （McMillan合成，2004年） 糖的合成IV （McMillan合成，2004年） 终极目标：理想全合成（Ideal Synthesis) * Why Total Synthesis? Discodermolide – sponge Discodermia dissoluta – antitumor, phase I – Source - total synthesis ? 39 steps gave 60g (0.65 % yield） Yondelis ET-743 – tunicate Ecteinascidia turbinata – antitumor, phase III – Source - semi-synthesis Why Total Synthesis? Synthesis and Structure Modification Why Total Synthesis? SAR studies and Lead Evaluation E7389 FDA 2010.11.15 乳腺癌 The Development of Organic Synthesis The Role of Total Synthesis 促进发展新的合成方法学和策略 Eschenmoser sulfide contraction 促进了解更加复杂的化学结构及理论 Woodward–Hoffmann rules Template synthesis 创造新的物质 培养人才 Linear Synthesis （线性合成） Several steps are performed one after another until the molecule is complete. ---- Time consuming ---- Low efficiency For 4 Linear Steps Overall Yield 90% per step 67% 60% per step 13% Convergent Synthesis （汇聚式合成） Individually prepared intermediates are convergently coupled together to make the target. ---- shorter route ---- simpler to operate ---- higher overall yields ---- high efficiency For 4 Linear Steps Overall Yield 90% per step 81% 60% per step 36% Target Convergent Synthesis of Biyouyanagin A K. C. Nicolaou, Angew. Chem. Int. Ed. 2007, 46, 4708-4711 3 steps 8 steps [2+2] cycloaddition Diversity Synthesis（多样性合成） Generate a library of structurally related chemical compounds. ---- good for structure-activity studies ---- high efficiency in generate structural diversity S. L. Schreiber, Angew