AI Article Synopsis
- - The study focuses on developing a new synthetic method for highly oxygenated cardiotonic steroids like ouabain, which are complex and challenging to produce.
- - The researchers used an unsaturation-functionalization strategy and a specific cyclization technique to create a key steroid structure (C19-hydroxy) in just four steps from a precursor compound.
- - This improved synthesis route led to the successful production of key steroids, 19-hydroxysarmentogenin and ouabagenin, highlighting its potential for creating new therapeutic agents efficiently.
Article Abstract
Highly oxygenated cardiotonic steroids, such as ouabain, possess a wide spectrum of biological functions and remain significant synthetic challenges. Herein, we have applied an unsaturation-functionalization strategy and developed a synthetic method in addressing the C19-hydroxylation issue for efficient synthesis of polyhydroxylated steroids. An effective asymmetric dearomative cyclization allowed the construction of the C19-hydroxy unsaturated steroidal skeleton in only four steps from the Hajos-Parrish ketone ketal 7. The synthetic sequence featured C3-OH-directed hydrogenation/epoxidation, m-CPBA-triggered epoxidation/S 2' nucleophilic substitution, Birch reduction of an enone, and regioselective LiAlH reduction to furnish the polyhydroxy functionalities on the steroid skeleton with high stereochemical control and efficiency. This approach ultimately enabled the total synthesis of 19-hydroxysarmentogenin and ouabagenin in 18 and 19 steps, respectively, overall. The synthesis of these polyhydroxylated steroids offers synthetic versatility and practicality in the search for new therapeutic agents.
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| http://dx.doi.org/10.1002/anie.202303639 | DOI Listing |
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