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

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

Arisa Chiba  1 , Ryoko Tanaka  1 , Mayuno Hotta  1 , Kayo Nakamura  1 , Kosho Makino  2 , Hidetsugu Tabata  3 , Tetsuta Oshitari  3 , Hideaki Natsugari  4 , Hideyo Takahashi  1
Affiliations

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

Arisa Chiba et al. Molecules. .

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Preparation of N-sulfonyl/acyl-5H-dibenzo[b,d]azepin-7(6H)-ones.
Scheme 2
Scheme 2
Synthesis of N-acyl-5H-dibenzo[b,d]azepin-7(6H)-ones. Reagents and Conditions: (i) BnOCOCl, K2CO3, THF, r.t., 9 days; (ii) BrCH2COOMe, NaH, DMF, 0 °C→r.t., 6 h; (iii) NaOH, MeOH, 0 °C→r.t., overnight; (iv) SOCl2, reflux, 1 h; (v) AlCl3, CH2Cl2, −78 °C→0 °C, 2 h; (vi) RCOCl, pyridine, THF, r.t., 1–2 h.
Figure 1
Figure 1
1H NMR spectra of E/Z isomer of N-acyl-5H-dibenzo[b,d]azepin-7(6H)-ones 2a–c.
Figure 2
Figure 2
HPLC of N-acyl-5H-dibenzo[b,d]azepin-7(6H)-ones 2a–c.
Figure 3
Figure 3
Time-dependent conversion rates (% ee) of 2a–c.
See this image and copyright information in PMC

References

    1. Zhang H.-H., Shi F. Organocatalytic atroposelective synthesis of indole derivatives bearing axial chirality: Strategies and applications. Acc. Chem. Res. 2022;55:2562–2580. doi: 10.1021/acs.accounts.2c00465. - DOI - PubMed
    1. Qin W., Liu Y., Yan H. Enantioselective synthesis of atropisomers via vinylidene ortho-quinone methides (VQMs) Acc. Chem. Res. 2022;55:2780–2795. doi: 10.1021/acs.accounts.2c00486. - DOI - PubMed
    1. Cheng J.K., Xiang S.-H., Tan B. Organocatalytic enantioselective synthesis of axially chiral molecules: Development of strategies and skeletons. Acc. Chem. Res. 2022;55:2920–2937. doi: 10.1021/acs.accounts.2c00509. - DOI - PubMed
    1. Sheng F.-T., Yang S., Wu S.-F., Zhang Y.-C., Shi F. Catalytic asymmetric synthesis of axially chiral 3,3’-bisindoles by direct coupling of indole rings. Chin. J. Chem. 2022;40:2151–2160. doi: 10.1002/cjoc.202200327. - DOI
    1. Hang Q.-Q., Wu S.-F., Yang S., Wang X., Zhong Z., Zhang Y.-C. Design and catalytic atroposelective synthesis of axially chiral isochromenone-indoles. Sci. China Chem. 2022;65:1929–1937. doi: 10.1007/s11426-022-1363-y. - DOI

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