Total Syntheses of Polyhydroxylated Steroids by an Unsaturation-Functionalization Strategy.
Jiawei Sun1, Yuan Chen1, Sherif Shaban Ragab1,2
1State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Ling Ling Road, Shanghai, 200032, China.
Angewandte Chemie (International Ed. in English)
|April 21, 2023
Summary
Researchers developed a new synthetic strategy for creating highly oxygenated cardiotonic steroids, overcoming key C19-hydroxylation challenges. This efficient method enables practical synthesis of complex polyhydroxylated steroids for potential therapeutic applications.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Synthetic Chemistry
Background:
- Highly oxygenated cardiotonic steroids, like ouabain, exhibit diverse biological functions.
- The synthesis of these complex polyhydroxylated steroids presents significant challenges, particularly C19-hydroxylation.
Purpose of the Study:
- To develop an efficient synthetic method for polyhydroxylated steroids.
- To address the C19-hydroxylation challenge in steroid synthesis.
- To enable the total synthesis of 19-hydroxysarmentogenin and ouabagenin.
Main Methods:
- Application of an unsaturation-functionalization strategy.
- Asymmetric dearomative cyclization for constructing the steroidal skeleton.
- Multi-step sequence including hydrogenation, epoxidation, nucleophilic substitution, and reduction.
Main Results:
- Successful construction of the C19-hydroxy unsaturated steroidal skeleton in four steps.
- High stereochemical control and efficiency in introducing polyhydroxy functionalities.
- Total synthesis of 19-hydroxysarmentogenin (18 steps) and ouabagenin (19 steps).
Conclusions:
- The developed synthetic approach offers versatility and practicality for polyhydroxylated steroid synthesis.
- This method facilitates the search for novel therapeutic agents based on cardiotonic steroids.
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