本論文為Pumiliotoxin、Allopumiliotoxin中間物1、2及河馬海棉酸A主結構53之合成研究。 化合物1為合成Pumiliotoxin的關鍵中間物。以L-脯胺酸作為起始物，經由保護胺基、酯化、甲基化後得到甲基酮化合物15。三氟醋酸對甲基酮15去保護後用乙烯葛林納試劑藉由螯合控制得到了d.e. > 95 % 之三級醇36。化合物36醯胺化後得到37，化合物37經由閉環置換及氫化得到了Pumiliotoxin中間物1。 化合物2為合成Allopumiliotoxin的中間物。以1為起始物，預期經由保護、環氧化、還原、氧化、去保護後得到化合物2。 化合物53為河馬海棉酸A的主架構。本論文描述了經由醇59和末端二取代烯55以氧化銀(silver oxide)條件進行耦合得到雙烯化合物64。進行閉環置換後得到具有環內雙鍵之哌喃65。化合物65以鈀金屬催化甲酸還原反應得到具有環外末端雙鍵之哌喃66。未來將會對66進行α亞甲基化得到68，最後鹼性條件下水解得到河馬海棉酸A的主要結構53。 This thesis describes the syntheses of the three key intermediates 1, 2 and 53 to Pumiliotoxin, Allopumiliotoxin and Hippospongic acid A . L-proline was converted to the N-BOC protected pyrrolidine ketone 15 through protection, esterification and methylation. Treating compound 15 with trifluoroacetic acid,and then vinylmagnesium bromide provided alcohol 36 with high diastereoselectivity by “chelation control”. After ring-closing metathesis and hydrogenation, Pumiliotoxin key intermediate 1 was obtained. After protection, expoxidation, reduction, oxidation and deprotection, indolizidine 1 should be converted to Allopumiliotoxin key intermediate 2. Compound 53 is the main framework of Hippospongic acid A . Coupling of alcohol 59 and ester 55 with silver oxide provided diene 64. After ring-closing metathesis and palladium-catalyzed formate reduction, compound 64 was converted to pyran 66 with a terminal alkene substituent. In the future, we expect that we can get α-methylene substituted ester 68 by α-methylenation. Compound 53 can be obtained after hydrolysis.
