Open AccessEnvironmentally Responsible and Cost-Effective Synthesis of the Antimalarial Drug Pyronaridine
Author(s) -
Joseph R. A. Kincaid,
Rahul D. Kavthe,
Juan C. Caravez,
Balaram S. Takale,
Ruchita R. Thakore,
Bruce H. Lipshutz
Publication year - 2022
Publication title -
organic letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.94
H-Index - 239
eISSN - 1523-7060
pISSN - 1523-7052
DOI - 10.1021/acs.orglett.2c00944
Subject(s) - chemistry , yield (engineering) , sequence (biology) , aqueous solution , pulmonary surfactant , combinatorial chemistry , drug , aqueous medium , catalysis , molecule , organic chemistry , stereochemistry , pharmacology , biochemistry , medicine , materials science , metallurgy
Two routes to the antimalarial drug Pyronaridine are described. The first is a linear sequence that includes a two-step, one-pot transformation in an aqueous surfactant medium, leading to an overall yield of 87%. Alternatively, a convergent route utilizes a telescoped three-step sequence involving an initial neat reaction, followed by two steps performed under aqueous micellar catalysis conditions affording Pyronaridine in 95% overall yield. Comparisons to existing literature performed exclusively in organic solvents reveal a 5-fold decrease in environmental impact as measured by E Factors.