Synthesis of Spiro-Isoxazolidine Derivatives of Methyl α-Isocostate

Author(s): Mohamed Zaki*, Abdelouahd Oukhrib, Mohammed Loubidi, Ahmed El Hakmaoui, Marie-Aude Hiebel, Mohammed Akssira, Sabine Berteina-Raboin.

Journal Name: The Natural Products Journal

Volume 9 , Issue 4 , 2019

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Abstract:

Background: In recent decades, natural products are an important source of chemotherapeutics as more than half of the effective cancer drugs can be traced to natural origins.

Objective: Moreover, the modification of natural products is one of the most common and fruitful approaches to obtain novel therapeutic agents in medicinal chemistry.

Methods: Continuing with a research project based on the support of Moroccan plant resources. we report herein the use of α-isocostic acid extracted in enantiomerically pure form from Dittrichia viscosa as a convenient starting material for the synthesis of new eudesmane derivatives.

Results: Novel spiro derivatives with a natural scaffold were prepared. Spiro-isoxazolidine derivatives were generated on the exocyclic double bond adjacent to the ester α,β-unsaturated function by 1,3-dipolar cycloaddition of methyl α-isocostate 1 derived from sesquiterpenic isocostic acid, with nitrones 2.

Conclusion: This procedure allowed us to generate enantiomerically pure spiro compounds in one diastereoisomer form with a limited number of steps. These compounds were fully characterized by spectroscopic methods.

Keywords: Dittrichia viscosa, isocostic acid, terpenes, 1, 3-dipolar cycloaddition, spiro-isoxazolidine, spectroscopic methods.

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VOLUME: 9
ISSUE: 4
Year: 2019
Page: [262 - 267]
Pages: 6
DOI: 10.2174/2210315508666180910124812
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