Methods for the preparation of 2,3,5-trimethylhydroquinone from 2,4,6-trimethylphenol (review)

Bushmelev, V. A.; Kondrat'eva, T. A.; Lipkin, M. A.; Kondrat'ev, Andrei V

doi:10.1007/bf00772128

Cited by 1 publication

(1 citation statement)

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“…After isolation and purification (11mgi solated), the product was analyzed by means of 1 H/ 13 CNMR spectroscopy and GC-MS and compared with values reported in the literature (see the Supporting Information). [21] Despite huge industrial interest in 2h ( % 90 patent applications), [31] there has been (to the best of our knowledge) no biocatalytic route described to show the conversion of 1b into 2h or 3b.I nt he case of 1a,o veroxidation of 2a and/or 2b enables the direct/linear synthesis of 3a without the need for additional catalysts/reactantso ri ntermediate isolation (Scheme1A). Thef ormation of 3a in the reactions with 1a (or 2a/2b)a sasubstrate revealed that all P450 BM3 enzymes were able to produce the desired vitaminE synthon.…”

Section: Engineering P450 Bm3 Toward Improved Conversion Of 1amentioning

confidence: 99%

An Enzymatic Route to α‐Tocopherol Synthons: Aromatic Hydroxylation of Pseudocumene and Mesitylene with P450 BM3

Dennig

Weingartner

Kardashliev

et al. 2017

Chemistry A European J

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Aromatic hydroxylation of pseudocumene (1 a) and mesitylene (1 b) with P450 BM3 yields key phenolic building blocks for α-tocopherol synthesis. The P450 BM3 wild-type (WT) catalyzed selective aromatic hydroxylation of 1 b (94 %), whereas 1 a was hydroxylated to a large extent on benzylic positions (46-64 %). Site-saturation mutagenesis generated a new P450 BM3 mutant, herein named "variant M3" (R47S, Y51W, A330F, I401M), with significantly increased coupling efficiency (3- to 8-fold) and activity (75- to 230-fold) for the conversion of 1 a and 1 b. Additional π-π interactions introduced by mutation A330F improved not only productivity and coupling efficiency, but also selectivity toward aromatic hydroxylation of 1 a (61 to 75 %). Under continuous nicotinamide adenine dinucleotide phosphate recycling, the novel P450 BM3 variant M3 was able to produce the key tocopherol precursor trimethylhydroquinone (3 a; 35 % selectivity; 0.18 mg mL ) directly from 1 a. In the case of 1 b, overoxidation leads to dearomatization and the formation of a valuable p-quinol synthon that can directly serve as an educt for the synthesis of 3 a. Detailed product pattern analysis, substrate docking, and mechanistic considerations support the hypothesis that 1 a binds in an inverted orientation in the active site of P450 BM3 WT, relative to P450 BM3 variant M3, to allow this change in chemoselectivity. This study provides an enzymatic route to key phenolic synthons for α-tocopherols and the first catalytic and mechanistic insights into direct aromatic hydroxylation and dearomatization of trimethylbenzenes with O .

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Section: Engineering P450 Bm3 Toward Improved Conversion Of 1amentioning

confidence: 99%