Biomimetic synthesis of galantamine via laccase/TEMPO mediated oxidative coupling

Abstract

Laccase-mediated intramolecular oxidative radical coupling of N-formyl-2-bromo-O-methylnorbelladine afforded a novel and isolable spirocyclohexadienonic intermediate of galantamine.

Laccase-Catalyzed 1,4-Dioxane-Mediated Synthesis of Belladine N-Oxides with Anti-Influenza A Virus Activity

“…The treatment of 7b (0.1 mmol) with laccase (1000 U·mmol −1 ) and TEMPO (2,2,6,6-tetra methyl-1-piperidinyloxy free radical, 0.06 mmol.) [ 35 , 36 ] at 25 °C for 3.0 h under O 2 atmosphere in 1,4-dioxane (0.5 mL) and sodium acetate buffer (2.0 mL; 0.5 M; pH 4.5) afforded 8 as the only recovered product, besides the unreacted substrate ( Scheme 1 ; Table 1 , entry 1) [ 8 ]. Examples of the retained activity of laccase in organic solvents are reported, and their advantages for the selectivity of the transformation are adequately discussed [ 37 , 38 ].…”

“…Recently, the use of N -formyl-2-bromo- O -methynorbelladine 7a in the total synthesis of 3 by a laccase (benzenediol: oxygen oxidoreductases, EC 1.10.3.2) [ 7 ]-mediator system has been reported, focusing on the formation of the spyrocyclohexadienone 6 as a tri-cyclic intermediate ( Figure 1 , Panel b) [ 8 ]. In this latter case, undesired side-products were produced depending on the nature of the N -substituent.…”

“…In this latter case, undesired side-products were produced depending on the nature of the N -substituent. Electron withdrawing group EW (R = CHO, 7a ) favored the formation of phenoxy radicals and successive oxidative coupling, and the hydrolysis of the iminium ion ( I ) to side-chain degradation products was the only observed side-process [ 8 , 9 ] ( Figure 1 ; Panel b, pathway a). Conversely, the oxidative coupling was not operative with electron-donating group ED (R = CH 3 , 7b ), in which case the isoindoline 8 was produced by an iminium-ion Polonovski transformation of the N -oxide intermediate ( II ) (not isolated) [ 10 , 11 ] ( Figure 1 ; Panel b, pathway b).…”

The Utility of Oxoammonium Species in Organic Synthesis: Beyond Alcohol Oxidation

“…Recently, Saladino et al reported the intramolecular dearomative coupling of tethered phenol using laccase-TEMPO catalysis; however, its applicability was not fully evaluated (Scheme 28b). 183 These facts indicate that the reactivity of oxoammonium species with phenol has not been fully investigated and that further studies must be conducted. The initial report on the oxoammonium salt-mediated oxidation of indoles was reported by Bobbitt et al…”

Oxidative Coupling of Coumarins by Blue‐LED‐Driven in situ Activation of Horseradish Peroxidase in a Two‐Liquid‐Phase System

“…The use of neat reaction conditions, or two‐liquid‐phase systems (2LPs), involving H 2 O and a water immiscible solvent, represent a promising strategy to overcome above mentioned drawbacks, increasing reagent loading and simplifying products recovery [27–31] . The application of ethereal solvents in organic and bioorganic catalyzed oxidation has been widely described, [32,33] and 2‐methyltetrahydrofuran (2‐Me‐THF) 1 (Figure 1) received a growing interest in recent years being a greener water‐immiscible alternative to toxic THF [34,35] . In addition, compound 1 is oxidized to the corresponding hydroperoxide 2 under blue‐LED driven condition by direct insertion of singlet oxygen at the tertiary α‐ethereal carbon atom (Figure 1), without formation of radical species [36] .…”