Kilogram-Scale Preparation of the Amino Alcohol Fragment of Selgantolimod by Enzymatic Resolution of an α,α-Disubstituted Amino Ester
The chiral amino alcohol (R)-2-amino-2-methylhexan-1-ol (1) is a key fragment in the synthesis of selgantolimod, a TLR8 agonist that is being evaluated for the treatment of hepatitis B infection. This report describes the development of a robust and scalable synthesis of the targeted amino alcohol f...
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| Veröffentlicht in: | Organic process research & development 2023-11, Vol.27 (11), p.2111-2122 |
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| container_title | Organic process research & development |
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| creator | Weinstein, Adam B. Bachrach, Florence J. Cagulada, Amy Regens, Christopher S. Zhang, Peng |
| description | The chiral amino alcohol (R)-2-amino-2-methylhexan-1-ol (1) is a key fragment in the synthesis of selgantolimod, a TLR8 agonist that is being evaluated for the treatment of hepatitis B infection. This report describes the development of a robust and scalable synthesis of the targeted amino alcohol featuring a hydrolase-catalyzed kinetic resolution of an α,α-disubstituted amino ester. The results highlight considerations for substrate design for the enzymatic resolution, the impact of pH on the resolution of an unprotected α,α-disubstituted amino ester derivative, and implementation of this substrate within a route to the desired amino alcohol fragment. |
| doi_str_mv | 10.1021/acs.oprd.3c00271 |
| format | Article |
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| source | ACS Publications |
| title | Kilogram-Scale Preparation of the Amino Alcohol Fragment of Selgantolimod by Enzymatic Resolution of an α,α-Disubstituted Amino Ester |
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