The synthesis of novel synthetic macrocycles containing both peptidic and polyketide-like domains
Permanent URL:
http://hdl.handle.net/2047/d20002533
Favaloro, Frank G. (Committee member)
Jones, Graham B. (Committee member)
Constantly striving to further diversify their libraries, and using design features from naturally occurring macrocycles where possible, Ensemble's latest endeavor is inspired by Jasplakinolide, a natural product of the sea sponge Jaspis johnstoni. Jasplakinolide is cell permeable and induces apoptosis in a number of tumor cell lines, including those related to renal, prostate, and breast cancer. Ensemble Therapeutics finds Jasplakinolide interesting not only because it is a biologically-active natural product, but also because of its structure. Jasplakinolide is a macrocycle that it incorporates not only a peptidic region (a feature of all of Ensemblin libraries at Ensemble Therepeutics), but also a polyketide-derived region, which the company had yet to explore in its libraries.
The newest library at Ensemble Therapeutics, Ensemble Library E, incorporates a polyketide-derived region utilizing reductive amination, a novel chemistry for Ensemblin libraries. The production of a pilot library of ELE-type macrocycles simultaneously verifies the intended chemistry for the ELE library and optimizes the synthetic route for these macrocycles on solid-phase.
pharmaceutical sciences
aldehyde
diol
macrocycle
polyketide
reductive amination
Macrocyclic compounds - Synthesis
Chemistry
Pharmacy and Pharmaceutical Sciences
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