Chiral squaramide-catalyzed asymmetric synthesis of pyranones and pyranonaphthoquinones via cascade reactions of 1,3-dicarbonyls with Morita–Baylis–Hillman acetates of nitroalkenes

Abstract

Cascade reactions of 1,3-dicarbonyls with Morita-Baylis-Hillman acetates of nitroalkenes using a quinine derived chiral squaramide organocatalyst led to the formation of pyranones and pyranonaphthoquinones in good to excellent yields and high diastereo- and enantioselectivities. Representative examples of the reaction scale-up with a much lower catalyst loading without an appreciable loss of selectivities and synthetic transformations of the products are also reported here. The compounds described herein for the first time were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease, since the structures are related to bioactive α-lapachones.

Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights

“…Recently, we reported a straightforward approach for the obtention of enantio-enriched α-lapachone derivatives [48]. In order to identify new enantio-enriched antitumor compounds, lawsone ( 41 ) was used to prepare the nitro-derivatives 42 and 43 via organocatalysis with a chiral squaramide (Scheme 7).…”

“…The previously published azido derivatives 5 , 9 , 14 , 20 , 25 , 39 , 46 were prepared as described in the literature [40-42,46-48]. Compound 28 (1.0 mmol) was prepared from 27 in the presence of sodium azide (120 mg, 1.85 mmol) in 2 mL of dimethylformamide (DMF).…”

“…Compound 28 was obtained after purification by column chromatography on silica gel eluting with a gradient mixture of hexane:ethyl acetate with increasing polarity. The unpublished azide derivative 47 was prepared following the same procedure previously described [48]. …”

Naphthoquinone-based chalcone hybrids and derivatives: synthesis and potent activity against cancer cell lines

“…30 Lawsone was reacted with Morita-Baylis-Hillman acetates of nitroalkenes in the presence of a quinine-squaramide organocatalyst to provide enantioenriched disubstituted a-lapachones. 30 Lawsone was reacted with Morita-Baylis-Hillman acetates of nitroalkenes in the presence of a quinine-squaramide organocatalyst to provide enantioenriched disubstituted a-lapachones.…”

“…30 In view of the ease of access to lapachone derivatives by selective chemical transformation of lapachol 7, we invested to study the corresponding hydrazone derivatives. 30 In view of the ease of access to lapachone derivatives by selective chemical transformation of lapachol 7, we invested to study the corresponding hydrazone derivatives.…”