Abstract
The first part of this thesis details the development of a second generation Diels-Alder approach to cis-clerodane natural products is described. The synthetic strategy takes advantage of the facile and highly face-selective Lewis acid mediated Diels-Alder cycloaddition reaction of dienophile 79, readily synthesized from 1,3-cyclohexanedione, to generate the cis-decalin core structure common to naturally occurring cis-clerodane diterpenoids. In addition to functioning as an activating group for the Diels-Alder reaction, the nitrile moiety was subsequently replaced with a methyl group in a completely diastereoselective manner and in one step. This reductive alkylation process for the installation of the cis-methyl group common to the vast majority of cis-clerodanoids is a significant improvement to our previous synthetic approach. The utility of this newly developed protocol towards the generation of stereo-defined cis-decalins is demonstrated in a more efficient synthesis of an advanced intermediate in our previous total synthesis of 6□-acetoxy-2-oxokolaven- ool (61) in racemic form. The application of this approach towards the asymmetric synthesis of (-)-61, starting with (-)-79, is also described herein. In the second part of this thesis, our study towards the total synthesis of the biologically active marine natural product dysidiolide (107) is described. The key step in our novel approach towards sesterterpenoid 107 was the generation of enone 171 from alcohol 62, readily synthesized from the cycloadduct of the zinc chloride mediated Diels-Alder cycloaddition reaction of the doubly activated dienophile 57 with trans-piperylene. Subsequent conjugate addition of a 4-methyl-4-pente- nyl moiety onto enone 171 afforded ketone 172 in a completely diastereoselective manner. Ketone 172 is the key intermediate in our proposed synthetic route to dysidiolide (107) and its synthesis constitutes part of this thesis. In the last section of this thesis, our endeavor towards the total synthesis of the marine natural product pallescensin C (179) via a cationic polyene cyclization methodology is presented. Starting with 3-ethoxy-6,6-dimethyl-2-cyclohexenone, 1,2-addition with 2-furyllithium followed by acid mediated hydrolysis of the resulting adduct furnished enone 204. Enone 204 was then carbomethoxylated, reduced, and oxidized to afford corss conjugated □-keto ester 203. Conjugate addition of an allyl moiety onto activated enone 203 yielded the polyene cyclization precursor 202, the key intermediate in our proposed synthesis of pallescensin C (179). The details of the synthesis of enone 202 as well as preliminary results in the cationic polyene cyclization reaction thereof constitutes is described.