An Efficacious Synthetic Strategy for cis-Clerodane Diterpenoids. Application to The Total Synthesis of Solidagolactone IV and V

• Main Authors: Yun-Lung-Ho, 何雲龍
• Other Authors: Hsing-Jang Liu
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/06850396035290469620

博士 === 國立清華大學 === 化學系 === 94 === Abstract The total synthesis of naturally occurring cis-clerodanoids solidagolactone IV and V has been accomplished in 16 and 17 linear steps respectively with the key step being a Diels-Alder cycloaddition to construct the bicyclic core common to both natural products. Starting from ethoxy enone 45, Stork-Danheiser alkylation with 4-bromo-1-butene gave enone 76 which was reduced and hydrolyzed to afford enone 77 in excellent yield. Cyano enone 80 was then arrived at from enone 77 via an established protocol of formylation (77 à 78), isoxazole formation (78 à 79), and base promoted fragmentation (79 à 80). The dienophilic carbon-carbon double bond was installed by treatment of enone 80 with DDQ under basic conditions, giving dienophile 73. Zinc (II) iodide mediated Diels-Alder cycloaddition of trans-piperylene with dienophile 73 furnished cycloadduct 82 possessing 3 of the 4 contiguous stereogenic centers present in the target molecules in the correct fashion. Reductive methylation of enone 82 afforded enone 84 with complete stereoselectivity which was subsequently subjected to a 1,4-addition reaction with lithium dimethylcuprate in the presence of trimethylsilyl bromide to install the final stereocenter found in the target natural products, yielded ketone 85. Treatment of ketone 85 with lithium aluminum hydride furnished alcohol 95 in a highly stereoselective manner, the alkoxy of which was protected as the MOM ether (95 à 102). Wacker oxidation of the terminal olefin present in compound 102 afforded methyl ketone 100 which oxidized to hydroxy ketone 101 in a 2-step process. Hydroxy ketone 101 was treated with triethyl phosphonoacetate under Horner Wadsworth Emmons reaction conditions to give butenolide 106 which was subsequently treated with rhodium trichloride in refluxing ethanol to complete the total synthesis of solidagolactone IV. From there, oxidation with pyridinium chlorochromate realized the total synthesis of solidagolactone V. The particulars of the abovementioned total syntheses is detailed in this thesis.