1. AlCl3 Mediated Aldol Condensation and Application to the Synthesis of Curcumin 2. Approaches Toward the Total Synthesis of Guanacastepene A

• Main Authors: Fong-Cheng Lee, 李芳城
• Other Authors: Chin-Kang Sha
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/sn5623

博士 === 國立清華大學 === 化學系 === 93 === Abstract The dissertation consists of two chapters. The first chapter describes the aluminum chloride catalyzed aldol condensation of α-iodo ketone 73 with various aliphatic ketones and aromatic aldehydes and then to synthesize the small-molecule antiangiogenic analogues of curcumin. According to the difference of substituent on aliphatic or aromatic ketones, this method could be applied to the synthesis of diversiform enones, β-hydroxy orβ-chloro ketones. Finally, the synthesis of Curcumin 62 was completed by using acetylacetone as starting material reacted with aluminum chloride and vanillin in an one-step procedure. The second chapter of this dissertation describes the study of the synthesis of Guanacastepene A (1). The starting material dienone 114b was synthesized from cycloheptanone in four steps. Diels-Alder reaction of 114b with trans-1,3-pentadiene using aluminum chloride as a catalyst gave compound 116 with the 7,6-fused ring skeleton. Treatment of 116 with diverse Grignard reagents in the presence of CuI and TMSCl were then converted to ketones 133 and 136 by produce silylenolethers 131 and 134. Compounds 131 and 134 α-iodination with NaI and m- CPBA , respectively. Furthermore, reaction of dienone 114b with Grignard reagent prepared from 4-iodo-1-trimethylsilyl-1-butyne and Mg to generate silylenolether 142, followed byα-iodination gave the α-iodo ketone 143. Application of radical cyclization of α-iodo ketone 143 using ditin gave compounds 114a and 114b with the 7,5- fused ring skeleton. On the other hand, the dienone 114a with β- methyl group was synthesized in two steps starting from phorone. Reaction of dienone 114a with Grignard reagent prepared from 5-bromo-1-pentene and Mg gave compound 186. Treatment of 186 with Oxone®, sodium bromide and triethylamine produce 190. Finally, reaction of 190 with DBU underwent intramolecular cyclization to construct the 7,6-fused ring skeleton 191 with two methyl group at C-7 and C-9a successfully.