TY - JOUR
T1 - Efficient and Scalable Asymmetric Total Synthesis of (−)-Emetine with Pharmaceutical Grade Quality; First Multigram Scale Synthesis
AU - Yamada, Masatoshi
AU - Azuma, Kazuki
AU - Takizawa, Iori
AU - Ejima, Yuki
AU - Yamano, Mitsuhisa
AU - Satoh, Kimio
AU - Doi, Takayuki
AU - Ueda, Hirofumi
AU - Tokuyama, Hidetoshi
N1 - Funding Information:
This work was supported in part by grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan, and the Japan Agency for Medical Research and Development, Tokyo, Japan (22ek0109449h0003). We are grateful to Dr. Hideya Mizufune for technical discussions. The authors would like to thank the following colleagues: Naoyuki Higuchi and Keiichi Sato for HRMS and specific rotation analysis.
Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/2/17
Y1 - 2023/2/17
N2 - A scalable asymmetric total synthesis of (−)-emetine, a natural product alkaloid from ipecac species and one of the main active ingredients in ipecac syrup used in emetics, has been accomplished. The synthetic route featured a total of 13 steps of highly efficient chemical reactions, including catalytic asymmetric allylation and an industrial deoxygenation of an aliphatic compound, which obviated the need for any chromatographic purification. (−)-Emetine·2HCl was obtained in 12% overall yield and over 93.2% HPLC purity. The synthesis was easily scaled up to 237.1 g and should be amenable to the production of larger quantities for ongoing drug development, while the compound is currently provided as natural ipecac syrup for a clinical use.
AB - A scalable asymmetric total synthesis of (−)-emetine, a natural product alkaloid from ipecac species and one of the main active ingredients in ipecac syrup used in emetics, has been accomplished. The synthetic route featured a total of 13 steps of highly efficient chemical reactions, including catalytic asymmetric allylation and an industrial deoxygenation of an aliphatic compound, which obviated the need for any chromatographic purification. (−)-Emetine·2HCl was obtained in 12% overall yield and over 93.2% HPLC purity. The synthesis was easily scaled up to 237.1 g and should be amenable to the production of larger quantities for ongoing drug development, while the compound is currently provided as natural ipecac syrup for a clinical use.
KW - (−)-emetine
KW - asymmetric allylation
KW - asymmetric hydrogenation
KW - deoxygenation of aliphatic compound
KW - natural product
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U2 - 10.1021/acs.oprd.2c00355
DO - 10.1021/acs.oprd.2c00355
M3 - Review article
AN - SCOPUS:85147151920
SN - 1083-6160
VL - 27
SP - 343
EP - 357
JO - Organic Process Research and Development
JF - Organic Process Research and Development
IS - 2
ER -