Dipolar Cycloaddition Approach toward Harmicine-Type Alkaloids: Synthesis and Stereochemical Determination
Zuming Lin1, Luyao Wu1, Shengchao Yang1
1School of Environmental and Chemical Engineering, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai 201418, People's Republic of China.
Abstract:
A rapid synthesis of harmicine was achieved through 1,3-dipolar cycloaddition and facile ring reconstruction, including mesylation, cleavage of the N-O bond, and subsequent cyclization. An enzymatic kinetic resolution was developed to obtain optically enriched tetrahydro-β-carboline, which was further elaborated to prepare harmicine. Additionally, diastereomeric synthesis of harmicinic acid was also achieved, and stereochemical determination was enabled by chemical resolution and electronic circular dichroism calculations for the first time, providing an intriguing platform to access various derivatives for future medicinal research.
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