1. Synthesis of Chiral 1,2-Amino Alcohol-Containing Compounds Utilizing Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of Unprotected α-Ketoamines.
- Author
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Mangunuru HPR, Terrab L, Janganati V, Kalikinidi NR, Tenneti S, Natarajan V, Shada ADR, Naini SR, Gajula P, Lee D, Samankumara LP, Mamunooru M, Jayaraman A, Sahani RL, Yin J, Hewa-Rahinduwage CC, Gangu A, Chen A, Wang Z, Desai B, Yue TY, Wannere CS, Armstrong JD 3rd, Donsbach KO, Sirasani G, Gupton BF, Qu B, and Senanayake CH
- Subjects
- Hydrogenation, Catalysis, Stereoisomerism, Molecular Structure, Amines chemistry, Amino Alcohols chemistry, Amino Alcohols chemical synthesis, Ruthenium chemistry
- Abstract
Herein, we disclose a facile synthetic strategy to access an important class of drug molecules that contain chiral 1,2-amino alcohol functionality utilizing highly effective ruthenium-catalyzed asymmetric transfer hydrogenation of unprotected α-ketoamines. Recently, the COVID-19 pandemic has caused a crisis of shortage of many important drugs, especially norepinephrine and epinephrine, for the treatment of anaphylaxis and hypotension because of the increased demand. Unfortunately, the existing technologies are not fulfilling the worldwide requirement due to the existing lengthy synthetic protocols that require additional protection and deprotection steps. We identified a facile synthetic protocol via a highly enantioselective one-step process for epinephrine and a two-step process for norepinephrine starting from unprotected α-ketoamines 1b and 1a , respectively. This newly developed enantioselective ruthenium-catalyzed asymmetric transfer hydrogenation was extended to the synthesis of many 1,2-amino alcohol-containing drug molecules such as phenylephrine, denopamine, norbudrine, and levisoprenaline, with enantioselectivities of >99% ee and high isolated yields.
- Published
- 2024
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