Chemoenzymatic Synthesis of a Chiral Ozanimod Key Intermediate Starting from Naphthalene as Cheap Petrochemical Feedstock.

Uthoff F, Löwe J, Harms C, Donsbach K, Gröger H (2019)
The Journal of organic chemistry 84(8): 4856–4866.

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Zeitschriftenaufsatz | Veröffentlicht | Englisch
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Abstract / Bemerkung
Ozanimod represents a recently developed, promising active pharmaceutical ingredient (API) molecule in combating multiple sclerosis. Addressing the goal of a scalable, economically attractive, and technically feasible process for the manufacture of this drug, a novel alternative synthetic approach toward ( S)-4-cyano-1-aminoindane as a chiral key intermediate for ozanimod has been developed. The total synthesis of this intermediate is based on the utilization of naphthalene as a readily accessible, economically attractive, and thus favorable petrochemical starting material. At first, naphthalene is transformed into 4-carboxy-indanone within a four-step process by means of an initial Birch reduction, followed by an isomerization of the C═C double bond, oxidative C═C cleavage, and intramolecular Friedel-Crafts acylation. The transformation of the 4-carboxy-indanone into ( S)-4-cyano-1-aminoindane then represents the key step for introducing the chirality and the desired absolute S configuration. When evaluating complementary biocatalytic approaches based on the use of a lipase and transaminase, respectively, the combination of a chemical reductive amination of the 4-carboxyindanone followed by a subsequent lipase-catalyzed resolution turned out to be the most efficient route, leading to the desired key intermediate ( S)-4-cyano-1-aminoindane in satisfactory yield and with excellent enantiomeric excess of 99%.
Erscheinungsjahr
Zeitschriftentitel
The Journal of organic chemistry
Band
84
Ausgabe
8
Seite(n)
4856–4866
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Uthoff F, Löwe J, Harms C, Donsbach K, Gröger H. Chemoenzymatic Synthesis of a Chiral Ozanimod Key Intermediate Starting from Naphthalene as Cheap Petrochemical Feedstock. The Journal of organic chemistry. 2019;84(8):4856–4866.
Uthoff, F., Löwe, J., Harms, C., Donsbach, K., & Gröger, H. (2019). Chemoenzymatic Synthesis of a Chiral Ozanimod Key Intermediate Starting from Naphthalene as Cheap Petrochemical Feedstock. The Journal of organic chemistry, 84(8), 4856–4866. doi:10.1021/acs.joc.8b03290
Uthoff, F., Löwe, J., Harms, C., Donsbach, K., and Gröger, H. (2019). Chemoenzymatic Synthesis of a Chiral Ozanimod Key Intermediate Starting from Naphthalene as Cheap Petrochemical Feedstock. The Journal of organic chemistry 84, 4856–4866.
Uthoff, F., et al., 2019. Chemoenzymatic Synthesis of a Chiral Ozanimod Key Intermediate Starting from Naphthalene as Cheap Petrochemical Feedstock. The Journal of organic chemistry, 84(8), p 4856–4866.
F. Uthoff, et al., “Chemoenzymatic Synthesis of a Chiral Ozanimod Key Intermediate Starting from Naphthalene as Cheap Petrochemical Feedstock.”, The Journal of organic chemistry, vol. 84, 2019, pp. 4856–4866.
Uthoff, F., Löwe, J., Harms, C., Donsbach, K., Gröger, H.: Chemoenzymatic Synthesis of a Chiral Ozanimod Key Intermediate Starting from Naphthalene as Cheap Petrochemical Feedstock. The Journal of organic chemistry. 84, 4856–4866 (2019).
Uthoff, Florian, Löwe, Jana, Harms, Christina, Donsbach, Kai, and Gröger, Harald. “Chemoenzymatic Synthesis of a Chiral Ozanimod Key Intermediate Starting from Naphthalene as Cheap Petrochemical Feedstock.”. The Journal of organic chemistry 84.8 (2019): 4856–4866.

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