Stereochemistry of N-Acyl-5 H-dibenzo[ b, d]azepin-7(6 H)-ones

Arisa Chiba; Ryoko Tanaka; Mayuno Hotta; Kayo Nakamura; Kosho Makino; Hidetsugu Tabata; Tetsuta Oshitari; Hideaki Natsugari; Hideyo Takahashi

doi:10.3390/molecules28124734

Stereochemistry of N-Acyl-5 H-dibenzo[ b, d]azepin-7(6 H)-ones

Molecules. 2023 Jun 13;28(12):4734. doi: 10.3390/molecules28124734.

Authors

Arisa Chiba¹, Ryoko Tanaka¹, Mayuno Hotta¹, Kayo Nakamura¹, Kosho Makino², Hidetsugu Tabata³, Tetsuta Oshitari³, Hideaki Natsugari⁴, Hideyo Takahashi¹

Affiliations

¹ Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.
² Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan.
³ Faculty of Pharma Sciences, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
⁴ Graduate School of Pharmaceutical Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Abstract

The stereochemical properties of N-acyl-5H-dibenzo[b,d]azepin-7(6H)-ones (2a-c), which inhibit potassium channels in T cells, were examined by freezing their conformational change due to 4-methyl substitution. N-Acyl-5H-dibenzo[b,d]azepin-7(6H)-ones exist as pairs of enantiomers [(a¹R, a²R), (a¹S, a²S)], and each atropisomer is separable at room temperature. An alternate procedure for preparing 5H-dibenzo[b,d]azepin-7(6H)-ones involves the intramolecular Friedel-Crafts cyclization of N-benzyloxycarbonylated biaryl amino acids. Consequently, the N-benzyloxy group was removed during the cyclization reaction to produce 5H-dibenzo[b,d]azepin-7(6H)-ones suitable for the subsequent N-acylation reaction.

Keywords: Kv1.3; atropisomer; axial chirality; dibenzoazepinone.

Grants and funding

22K06537/Japan Society for the Promotion of Science