Research Progress in Enzymatic Synthesis of Vitamin E Ester Derivatives

Vitamin E is easily oxidized by light, air, oxidizing agents and heat, limiting its application in many ways. Compared to vitamin E, vitamin E ester derivatives exhibit improved stability and a stronger antioxidant capacity, and even gain new biological functions. In recent years, enzymatic synthesis of vitamin E ester derivatives has received increasing attention due to its environmental friendliness, high catalytic efficiency, and inherent selectivity. This paper reviews the related progress of lipase-mediated preparation of vitamin E ester derivatives. The function of different vitamin E ester derivatives, and the main factors influencing the enzymatic acylation process, including enzyme species, acyl donor and acceptor, reaction media and water activity, are summarized in this paper. Finally, the perspective of lipase-catalyzed synthesis of vitamin E ester derivatives is also discussed.

Lipase-catalyzed selective esterification of catechin

Catechins show strong antioxidant, antitumoral, antiviral, and anti-inflammatory activities. The uses of catechins in food, cosmetic, and pharmaceutical formulations seem very attractive. Unfortunately, solubility and stability of catechins are poor in apolar media, which limits their efficient uses. In order to improve the solubility of catechins in the oil phase and maintain their oxidation resistance, a regioselective enzymatic acylation was investigated. The effects of reaction medium, water content, carbon chain length of acyl donor and other factors on the acylation reaction were studied, catechins were enzymatically esterified with an aliphatic acid (stearic acid) using an immobilized lipase Novozym 435 in n-butanol. The results show that when the ratio between catechins and stearic acid was 1:5, adding molecular sieves 4A after 11 h of reaction and the temperature of 60 °C led to the maximum conversion yield of 60.36%. Studies have shown that catechin stearate has a higher antioxidant activity than vitamin E and dibutyl hydroxytoluene (BHT).

Effects of Cyanidin-3-Glucoside Derived from Black Rice (Oryza Sativa L.) and Enzymatically Acylated Cyanidin-3-Glucoside Lauryl Ester on Intestinal Microorganisms In Vitro

In this paper, cyanidin-3-glucoside was isolated and purified from black rice, then enzymatic acylation with lauric acid to obtain cyanidin-3-glucoside lauryl ester. The structure of cyanidin-3-glucoside lauryl ester was characterized by liquid chromatography electrospray ionization tandem mass spectrometry and Fourier transform infrared spectroscopy. Then the potential proliferative effect on probiotics and inhibitory effect on harmful bacteria of cyanidin-3-glucoside and cyanidin-3-glucoside lauryl ester were studied in vitro. The effects of cyanidin-3-glucoside and cyanidin-3-glucoside lauryl ester on the composition of human fecal intestinal flora and its metabolic pathway were also analyzed through 16S ribosomal ribonucleic acid high-throughput sequencing and gas chromatography-mass spectroscopy, respectively. The results indicated that cyanidin-3-glucoside lauryl ester was better than cyanidin-3-glucoside in promoting the growth of B. adolescentis, B. infantis, L. thermophiles, and L. acidophilus as well as inhibiting the growth of S. dysenteriae, Y. enterocolitica, S. enteritidis, and S. typhi. Additionally, the proliferative effect of cyanidin-3-glucoside lauryl ester was significantly improved in a lower media pH due to the intestinal microbial metabolism to produce more organic acids, such as propionic acid, phenyllactic acid, and lauric acid. The study will provide a theoretical basis for the application of cyanidin-3-glucoside lauryl ester in the intestinal health.

Progress Towards a Large-Scale Synthesis of Molnupiravir (MK-4482, EIDD-2801) from Cytidine

<div> <div> <div> <p>Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for treatment of COVID-19. Herein we describe a supply-centered and chromatography-free synthesis of molnupiravir from cytidine, consisting of two steps: a selective enzymatic acylation followed by transamination to yield the final drug product. Both steps have been successfully performed on decagram scale: the first step at 200 g, and the second step at 80 g. Overall, molnupiravir has been obtained in a 41% overall isolated yield compared to a maximum 17% isolated yield in the patented route. This route provides many advantages to the initial route described in the patent literature and would decrease the cost of this pharmaceutical should it prove safe and efficacious in ongoing clinical trials.</p> </div> </div> </div>

Progress Towards a Large-Scale Synthesis of Molnupiravir (MK-4482, EIDD-2801) from Cytidine

<div> <div> <div> <p>Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for treatment of COVID-19. Herein we describe a supply-centered and chromatography-free synthesis of molnupiravir from cytidine, consisting of two steps: a selective enzymatic acylation followed by transamination to yield the final drug product. Both steps have been successfully performed on decagram scale: the first step at 200 g, and the second step at 80 g. Overall, molnupiravir has been obtained in a 41% overall isolated yield compared to a maximum 17% isolated yield in the patented route. This route provides many advantages to the initial route described in the patent literature and would decrease the cost of this pharmaceutical should it prove safe and efficacious in ongoing clinical trials.</p> </div> </div> </div>