Synthetic Studies on Antineoplastic Agent D-501036 and Cadinane Sesquiterpenoids

• Main Authors: Wan-Jeng Wang, 王萬珍
• Other Authors: Hsing-Jang Liu
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/95665247298401807368

碩士 === 國立清華大學 === 化學系 === 94 === The first part of this thesis describes the research towards an optimized synthesis process for D-501036 in support of the drug discovery efforts of the Development Center for Biotechnology. Diketone 18 was obtained via a Freidel-Crafts acylation process starting with selenophene and succinic chloride which was subsequently condensed with methylamine hydrochloride in the presence of sodium acetate to form the highly congested N-methyl pyrrolo compound 20. Pyrrole 20 was transformed to the target molecule D-501036 in 3 steps. In this way, a 5 step process towards this highly novel therapeutically valuable compound was developed. The second part of this thesis details the investigation towards the asymmetric total synthesis of naturally occurring sesquiterpenoids of the cadinene family, namely 10-isocyano-4-cadinene (30), 10-isothiocyanato-4-cadinene (31), and 10-isothiocyanatocadin-6-ene (32). The total synthesis approach called for the generation of dienophile 55 from commercially available (-)-b-pinene (44), Diels-Alder cycloaddition of 55 with isoprene to construct the decalin core, followed by a sequence of reactions to arrive at naturally occurring trans-decalins a-cadinol (39) and T-cadinol (41), which were readily separated. With these epimeric alcohols in hand, it is believe that the final transformations (i.e. 39 à 30, 31 and 41 à 32) will be arrived at trivially.