Application of the prins cyclization to a synthesis of the tetrahydropyran rings of lasonolide A
This thesis describes studies toward the synthesis of the tetrahydropyran-containing marine macrolide lasonolide A. A summary of studies done by Lee and coworkers, that led to a revision of the structure as well as its first total synthesis is presented. This is followed by a literature review of the partial and completed syntheses of lasonolide A reported by other groups. The studies presented are based on the use of a Prins cyclization as the key reaction. The cyclization uses vinylogous carbonates as the source to generate the oxocarbenium ion. Therefore, we first introduce the background that led to the development of this reaction. The Prins cyclizations were promoted using trifluoroacetic acid and the products were immediately hydrolyzed to afford in most of the cases the tetrahydropyran rings as the major product. The cyclization of alkyne derived vinylogous carbonates resulted in instability of the product to the reaction conditions. Also, formation of 5-membered ring was a competing pathway. Vinlogous carbonates derived from Z-alkenes gave the all cis-2,3,4,6-tetrahydropyran in 59-70% yield. The E-alkene derived enol ethers gave the C3 epimeric tetrahydrofuran. Inversion of the secondary alcohol in the tetrahydropyran ring was partially accomplished using a Mitsunobu reaction. This methodology led to the racemic and asymmetric syntheis of the B ring of lasonolide A. The racemic synthesis was accomplished in 8 steps from 3-buten-1-ol. An asymmetric synthesis was also accomplished in 12 steps from (R)-malic acid. The quaternary stereogenic center of the A ring of lasonolide A was constructed via C-H insertion reaction using Doyle’s catalyst (Rh2(4R-MEOX)4).
School:The Ohio State University
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:lasonolide a prins cyclization vinylogous carbonate enol ether asymmetric synthesis
Date of Publication:01/01/2004