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Short Paper | Regular issue | Vol 100, No. 1, 2020, pp.129-136
Published online, 20th September, 2019
DOI: 10.3987/COM-19-14118
Syntheses of Indirubins by Aldol Condensation of Isatins with Indoxyl Anion Generated in situ by Lipase-Catalyzed Deacetylation of Indoxyl Acetate

Takeshi Sugai,* Kengo Hanaya, and Shuhei Higashibayashi

*Department of Pharmaceutical Sciences, Faculty of Pharmacy, Keio University, 1-5-30 Shiba-Kouen, Minato-ku, Tokyo, Japan

Abstract

The syntheses of indirubin (76% yield), 6-bromoindirubin (82% yield), and 6-bromoindirubin-3′-oxime (78% yield in two steps) were achieved via the lipase-triggered aldol condensation between isatins and an indoxyl anion in tetrahydrofuran under anhydrous and anaerobic conditions as the key step. The aldol donor was generated in situ by Burkholderia cepacia lipase (Amano PS-IM)-catalyzed deacetylation of commercially available and stable indoxyl acetate in the presence of triethylamine and with 2-propanol as the transesterification reagent. The scale-up of the presently developed reactions is easier than that in the previously reported chemical aldol condensations, because of the simplicity of the isolation procedure and suppression of the oxidative byproduct formation from indoxyl acetate.