Biocatalytic decarboxylative Michael addition for synthesis of 1,4-benzoxazinone derivatives

Abstract

The Candida antarctica lipase B (Novozym 435) is found to catalyze a novel decarboxylative Michael addition in vinylogous carbamate systems for the synthesis of 1,4-benzoxazinone derivatives. The reaction goes through Michael addition, ester hydrolysis and decarboxylation. A possible mechanism is suggested, with simultaneous lipase-catalyzed Michael addition and ester hydrolysis. The present methodology offers formation of complex products through multi-step reactions in a one pot process under mild and facile reaction conditions with moderate to high yields (51–90%) and no side product formation. The reaction seems to be is a great example of enzymatic promiscuity.

Biocatalytic synthesis of oxadiazole thioethers and evaluation of their antitumor activity

“…On this basis, according to control experiments and previous reports, 35 we propose a possible mechanism for this lipase-catalyzed decarboxylative Knoevenagel-thia Michael addition. As presented in Scheme 3 (illustrated with the reaction from entry 3, Table 3), firstly, the Asp-His dyad assists the ethyl butyryl acetate in forming the enol, which is stabilized by the oxyanion hole in the active site.…”

“…[19][20][21][22][23][24] Hence, lipases are not only used for catalyzing conventional reactions, such as hydrolysis, transesterification, esterification, [25][26][27] and kinetic resolutions, [28][29][30] but also unconventional reactions. 31,32 Indeed, different chemical transformations catalyzed by lipases to form C-C, C-N, and C-S bonds through promiscuous mechanisms have been reported, 31 some of which are the Knoevenagel condensation, 33 Michael addition, 34,35 aldol, 20 Hantzsch, 21 Mannich 22 and Cannizzaro reactions. 23 Knoevenagel condensations, as a variant of aldol condensations, are one of the fundamental reactions in organic synthesis to form carbon-carbon double bonds.…”

Synthesis of Benzoxazines by Heterogeneous Multicomponent Biochemo Multienzymes Cascade Reaction

“…Benzoxazines are heterocyclic derivatives , characterized by different biological activities, including neuroprotective, anticancer, and antioxidant properties . They are usually synthesized by harsh and tedious multistep reactions, , the only exception being a limited number of procedures based on heavy metals or, in alternative, electrochemistry .…”

“…Benzoxazines are heterocyclic derivatives 1,2 characterized by different biological activities, including neuroprotective, 3 anticancer, 4 and antioxidant properties. 5 They are usually synthesized by harsh and tedious multistep reactions, 6,7 the only exception being a limited number of procedures based on heavy metals 8 or, in alternative, electrochemistry. 9 Multienzymes cascade reactions 10 and multicomponent chemistry 11 are considered as a sustainable and green alternatives for the synthesis of heterocyclic derivatives.…”