TitleSynthesis of the 16-membered BCD ring of complestatin and halogenation of the tryptophan indole
NameMootoosammy, Davena (author), Jimenez, Leslie (chair), Hultzsch, Kai (internal member), Taylor, John (internal member), Rutgers University, Graduate School - New Brunswick,
SubjectChemistry and Chemical Biology,
DescriptionComplestatin is a natural product that has demonstrated inhibition activity against HIV-1 integrase and initiation of the complement pathway. Though its biological activity is proven, the total synthesis of the molecule is challenging in many ways. In this thesis the synthetic strategy taken for the partial synthesis of the BCD ring fragment of Complestatin is described. Part of the synthetic studies on the BCD ring involves using the mild conditions to limit isomerization of the sensitive phenylglycine subunits. This was achieved by using DEPBT and HATU as coupling reagents that limit epimerization during condensation. Oxidative phenol coupling is used to form a biaryl ether bond between the L-tyrosine and 4-hydroxyphenylglycine subunits to synthesize the BCD ring. Previous syntheses to form this bond require the functionalization of the subunits. It is our goal to limit the synthesis by decreasing the amount to steps necessary to form the BCD ring, which is accomplished using this method. Our synthesis of the BCD ring is 6 steps from 4-hydroxyphenylglycine, with approximately 10% overall yield. The investigation into the synthesis of Complestatin evolves around the synthesis of 6-bromotryptophan. In order to limit the amount of steps in the total synthesis, the project for the facile synthesis of 6-bromotryptophan was undertaken. It was found that the Boc protecting group on the amino group provided efficient protection of the 2-position on the indole, leading to the formation of 5-bromotryptophan. The synthesis of the TMC-95A southern fragment was also accomplished through a series of peptide couplings.
NoteIncludes bibliographical references
Noteby Davena Mootoosammy
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.