Strain Release Methodology for the Synthesis of Actinonin and Epi-Actinonin. Synthesis of New TNCA Derivatives as Calcium Sensing Receptor Ther(G)Nostic and PET Imaging Agent
Year: 2025
Type: dissertation
Abstract: Diazo-carbonyl compounds are versatile synthetic intermediates known for their role in the construction of complex organic molecules and natural products. In this study, we report a concise and efficient nine-step total synthesis of the naturally occurring antibiotic Actinonin and its diastereomer epi-actinonin, using strain release Methodology. The synthetic route begins with the preparation of a β-keto ester scaffold using Meldrum’s acid, followed by diazo transfer to form a diazoenolate intermediate. Silyl protection yields a stable enol diazoacetate, which serves as a carbene precursor for stereoselective Cyclopropenation. Parallel synthesis of a valine-derived dipeptide is achieved through CDI-mediated coupling and Boc-deprotection. The key Cyclopropenation step, catalyzed by Rh(II), proceeds via strain-release to yield a mixture of diastereomers. Subsequent nucleophilic substitution of the ester moiety with hydroxylamine affords the final hydroxamic acid derivatives. Moreover, we report on the synthesis of new derivatives of TNCA β-carbolines for the Calcium Sensing Receptor Thera(g)nostics and PET Imaging Agents
Source: Digital Archive @ GSU
DOI: 10.57709/rsk1-b376
Author: Khan, Muhammad Munib
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W6973956096
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