Total synthesis of natural products provides an avenue for investigation of complex chemical scaffolds, not only delivering access to biologically impactful molecules but also lending a deeper understanding of their inherent chemical reactivity. Expansion of reaction methodology, optimization of biological activity, and absolute structural confirmation can all be accomplished via the targeted total synthesis of natural products. The solamin stereoisomers are a family of bioactive natural products whose stereocomplex structures have been the focus of many total synthesis efforts. This work outlines a novel and stereodivergent approach towards the solamin stereoisomers, featuring an application of a “traceless” Petasis methodology developed previously by the Thomson and Schaus groups for the construction of chiral allene intermediates. In this enantio- and diastereoselective method, allenols are constructed that are capable of undergoing intramolecular cyclization reactions, ultimately providing stereodefined 2,5-dihydrofuran cores as precursors to the solamin stereoisomers. The outlined application of this transformation towards the solamin stereoisomers both expands the scope of the reaction methodology and provides an yet-unreported, modular approach towards these sought-after natural product targets. Tambromycin, a novel peptide natural product with modest biological activity, was discovered via a targeted natural product discovery approach termed metabologenomics. Given the unique structural characteristics and bioactivity of tambromycin, the total synthesis of this compound was targeted featuring an application of C–H functionalization, as well as stereocontrolled amination. Access to the natural product has thus led to an avenue for further investigation into its bioactivity, with structure–activity relationship and target–identification studies both possible.

Creator

• Rote, Jennifer

DOI

• https://doi.org/10.21985/n2-26qk-fc85

Subject

• Organic chemistry
• Chemistry

Language

• en

Alternate Identifier

• http://dissertations.umi.com/northwestern:15164
• etdadmin_upload_750061

Keyword

• allene
• total synthesis
• peptide
• traceless Petasis reaction
• natural product
• organic synthesis

Date created

• 2020-01-01

Resource type

• Dissertation

Rights statement

• In Copyright