TitleAllene-based approach to the synthesis of De Novo erythromycinoids
NameKim, Hiyun (author), Williams, Lawrence J (chair), Warmuth, Ralf (internal member), Hultzsch, Kai C (internal member), Hu, Longqin (outside member), Rutgers University, Graduate School - New Brunswick,
SubjectChemistry and Chemical Biology,
DescriptionWe prepared an advanced synthetic module (bis[allene] macrolactone at center) equipped with two allenes embedded in a macrolactone scaffold. The plan was to effect heterogeneous derivatization of the allenes, in tandem or separately. In addition to diversity, this approach is maximally concise and economic, especially in terms of steps. Moreover, immediate derivatives of the macrocyclic bis[allene] can be taken into further steps, thus providing canonical build-up of erythromycin analogs. To date, our bis[allene] macrolactone has been converted to over 30 novel macrolides. These de novo analogs serve to validate the strategy and lay the ground work for further work. Taken together, the allene-based reactions/transformations employed in this study, such as DMDO oxidation/nucleophile addition, allene osmylation/electrophile addition, bromination, allene oxide rearrangement, spirodiepoxide rearrangement, benzylic migration/elimination, mono- and bis-oxidation of bis[allene], chelation-controlled reduction and oxime formation, demonstrate that 8 of the 11 modifiable carbons in this antibiotic can be modified. It is especially noteworthy that each congener was made in less than three steps from the bis[allene] macrolactone.
NoteIncludes bibliographical references
Noteby Hiyun Kim
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.