A Formal Synthesis of Optically Active 2-Oxo-5a,8a-13, 14, 15, 16-tetranorclerod-3-en-12-oic acid and 6b-Acetoxy-2-oxokolavenool

• Main Authors: In-Shan Sir, 余怡璇
• Other Authors: Hsing-Jang Liu
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/28722707780221296276

碩士 === 國立清華大學 === 化學系 === 88 === This thesis describes the formal asymmetric synthesis of 2-oxo-5a,8a-13,14,15,16-tetranorclerod-3-en-12-oic acid (54) and 6b-acetoxy-2-oxokolavenool (55) (Figure 1). The efficient synthesis of (R)-4-(2-benzyloxyethyl)-4-methyl-2-cyclohexenone [(-)-67], a common intermediate in a previously reported synthesis of both 54 and 55, in an asymmetric manner was the key concept in this approach. Towards this end, two approaches were investigated: enzymatic kinetic resolution and asymmetric synthesis via Meyer''s b-lactam approach to 4,4-disubstituted 2-cyclohexenones. In the first approach, kinetic resolution of a racemic mixture of 4-(2-benzyloxyethyl)-4-methyl-2-cyclohexenone as mediated by lipase AK did not result in a sufficiently high level of asymmetric resolution. However, during our investigations, we developed a new procedure to effectively resolve a racemic mixture of 2-phenylcyclohexanol (94) into its individual chiral forms quantitatively. In the approach using Meyer''s b-lactam ([2S-(2a,3b,8ab)]-(+)-hexahydro-3-(hydroxymethyl)-8a-methyl-2-phenyl-5H-oxazo-lo[3,2-a]pyridin-5-one, 87) as starting material, compound (-)-67 was realized in excellent optical and synthetically useful yields. The enantiomer of (-)-67, compound (+)-67, was also synthesized via this chemical approach in excellent optical and synthetically useful yields. Compound (+)-67 was further elaborated to Diels-Alder adducts (+)-70 and 92 containing the core decalin structure of cis-ent-clerodane natural products. The details of our investigations are described in this thesis.