Asymmetric Biomimetic Oxidations of Phenols: The Mechanism of the Diastereo- and Enantioselective Synthesis of Thomasidioic Acid

Abstract

Enantiopure chiral amidic derivatives of sinapic acid were oxidised with hydrogen peroxide using horseradish peroxidase (HRP) as the catalyst to give the aryltetraline dilignol thomasidioic acid. Trans-diastereoselectivity and enantioselectivity in the formation of thomasidioic acid was observed. Computational methods show that the enantioselectivity is controlled by the β-β oxidative coupling step, while the diastereoselectivity is controlled by the stability of the reactive conformation of the intermediate quinomethide.

Single- and multi-component chiral supraparticles as modular enantioselective catalysts

“…It needs to be pointed out that enantioselectivity of oxidative phenol coupling, which is Tyr–Tyr dimerization is representative of, is both difficult 40,41 due to low chiral bias and significant due to variety of biomedical needs 41 . The problems with enantioselectivity are particularly noticeable for low molecular weight phenols as opposed to large molecular 42 weight polycyclic aryls 43 . As such, optical purity of just a few percent is typically achieved even with complex metalorganic catalysts for diverse catalytic substrates 42 .…”

“…The photocatalytic processes in inorganic SPs mimic Tyr dimerization in photosynthetic bacterial organelles 39 , demonstrating functional replication of biological nanoscale assemblies. Furthermore, enantioselectivity for Tyr–Tyr has not been reported due to lack of efficient catalysts 40,41 while asymmetric oxidative coupling of other phenols was shown to be difficult to achieve even with sophisticated metal-organic catalysts 42,43 . The catalytic functions in these assemblies can be optimized by taking advantage of SP modularity, combining NPs with different chemical and optical properties.…”

Bioinspired Syntheses of Dimeric Hydroxycinnamic Acids (Lignans) and Hybrids, Using Phenol Oxidative Coupling as Key Reaction, and Medicinal Significance Thereof

“…Zoia and coworkers developed an enantioselective biomimetic approach to synthesize ThoA ( 8 ) [44]. They subjected amides 47a – c of SinA with chiral amines, such as ( S )-Phe ethyl ester, ( S )-methylbenzylamine and ( S )-2-phenyloxazolidinone, the latter acting as chiral auxiliaries, to POC using hydrogen peroxide as oxidant and HRP as catalyst in a dioxane-water, buffered at pH 4, solution.…”

“…Amides I ( 48a – c ) could be hydrolyzed to ThoA ( 8 ) with LiOOH in THF-H 2 O in 10%–60% yields, the highest one obtained with the amide ( 48a – I ) from ( S )-2-phenyloxazolidinone. Computational methods showed that enantio- and diastereoselectivity are controlled by the β-β oxidative coupling step and the stability of the reactive conformation of the intermediate quinonemethide, respectively [44].…”

Podophyllotoxin and Antitumor Synthetic Aryltetralines. Toward a Biomimetic Preparation

“…6.2 Enzyme-catalyzed oxidative phenol coupling a: ) Amide (63), submitted to oxidative phenol coupling with hydrogen peroxide in the presence of horseradish peroxidase gave a mixture of the levorotatory isomer of the aryltetraline cannabisin (64), having a 1,2-cis stereochemistry and a 3,4 double bond, and the phenylcoumaran grossamide, (65) (Scheme 19) (Lajide et al, 1995). (Zoia et al, 2008). The proposed reaction pathway involves two steps; the first step is the 8-8 oxidative coupling of two phenoxy radicals (67) to give the bisquinomethide (68) , and the second step is the ring closure of (68) to give the final product.…”