Dataset Information

Optimization of the Lipase-Catalyzed Selective Amidation of Phenylglycinol.

ABSTRACT: Ceramides and their analogs have a regulatory effect on inflammatory cytokines expression. It was found that a kind of ceramides analog synthesized from phenylglycinol could inhibit the production of cytokine TNF-?. However, two active hydrogen groups are present in the phenylglycinol molecule. It is difficult to control the process without hydroxyl group protection to dominantly produce amide in the traditional chemical synthesis. A selective catalytic the amidation route of phenylglycinol by lipases was investigated in this research. The results indicated that the commercial immobilized lipase Novozym 435 has the best regio-selectivity on the amide group. Based on the experimental results and in silico simulation, it was found that the mechanism of specific N-acyl selectivity of lipase was not only from intramolecular migration and proton shuttle mechanism, but also from the special structure of active site of enzyme. The optimal reaction yield of aromatic amide compound in a solvent-free system with lipase loading of 15 wt% (to the weight of total substrate) reached 89.41 ± 2.8% with very few of byproducts detected (0.21 ± 0.1% ester and 0.64 ± 0.2% diacetylated compound). Compare to other reported works, this work have the advantages such as low enzyme loading, solvent free, and high N-acylation selectivity. Meanwhile, this Novozym 435 lipase based synthesis method has an excellent regio-selectivity on most kinds of amino alcohol compounds. Compared to the chemical method, the enzymatic synthesis exhibited high regio-selectivity, and conversion rates. The method could be a promising alternative strategy for the synthesis of aromatic alkanolamides.

SUBMITTER: Sun M

PROVIDER: S-EPMC6987038 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Optimization of the Lipase-Catalyzed Selective Amidation of Phenylglycinol.

Sun Meina M Nie Kaili K Wang Fang F Deng Li L

Frontiers in bioengineering and biotechnology 20200122

Ceramides and their analogs have a regulatory effect on inflammatory cytokines expression. It was found that a kind of ceramides analog synthesized from phenylglycinol could inhibit the production of cytokine TNF-α. However, two active hydrogen groups are present in the phenylglycinol molecule. It is difficult to control the process without hydroxyl group protection to dominantly produce amide in the traditional chemical synthesis. A selective catalytic the amidation route of phenylglycinol by l ...[more]

PMID: 32039186

Similar Datasets

Project description:We report a set of rare copper-catalyzed reactions of alkanes with simple amides, sulfonamides, and imides (i.e., benzamides, tosylamides, carbamates, and phthalimide) to form the corresponding N-alkyl products. The reactions lead to functionalization at secondary C-H bonds over tertiary C-H bonds and even occur at primary C-H bonds. [(phen)Cu(phth)] (1-phth) and [(phen)Cu(phth)2] (1-phth2), which are potential intermediates in the reaction, have been isolated and fully characterized. The stoichiometric reactions of 1-phth and 1-phth2 with alkanes, alkyl radicals, and radical probes were investigated to elucidate the mechanism of the amidation. The catalytic and stoichiometric reactions require both copper and tBuOOtBu for the generation of N-alkyl product. Neither 1-phth nor 1-phth2 reacted with excess cyclohexane at 100 °C without tBuOOtBu. However, the reactions of 1-phth and 1-phth2 with tBuOOtBu afforded N-cyclohexylphthalimide (Cy-phth), N-methylphthalimide, and tert-butoxycyclohexane (Cy-OtBu) in approximate ratios of 70:20:30, respectively. Reactions with radical traps support the intermediacy of a tert-butoxy radical, which forms an alkyl radical intermediate. The intermediacy of an alkyl radical was evidenced by the catalytic reaction of cyclohexane with benzamide in the presence of CBr4, which formed exclusively bromocyclohexane. Furthermore, stoichiometric reactions of [(phen)Cu(phth)2] with tBuOOtBu and (Ph(Me)2CO)2 at 100 °C without cyclohexane afforded N-methylphthalimide (Me-phth) from ?-Me scission of the alkoxy radicals to form a methyl radical. Separate reactions of cyclohexane and d12-cyclohexane with benzamide showed that the turnover-limiting step in the catalytic reaction is the C-H cleavage of cyclohexane by a tert-butoxy radical. These mechanistic data imply that the tert-butoxy radical reacts with the C-H bonds of alkanes, and the subsequent alkyl radical combines with 1-phth2 to form the corresponding N-alkyl imide product.

Dataset Information

Optimization of the Lipase-Catalyzed Selective Amidation of Phenylglycinol.

Publications

Optimization of the Lipase-Catalyzed Selective Amidation of Phenylglycinol.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets