Novel One-Pot Green Synthesis of Indolizines Biocatalysed by Candida antarctica Lipases

Abstract

Marine microorganisms are of considerable interest as a promising source of enzymes with unsuspected potentials as catalysts for chemical synthesis. We describe here an efficient method for one-pot indolizine synthesis that has been developed using lipase A and lipase B from Candida antarctica as biocatalysts. As showed by HPLC/MS analysis, the yield in indolizines was higher in the presence of the biocatalyst than in absence of enzyme. Lipase A, from Candida antarctica, showed high catalytic activity and selectivity for the cycloaddition reactions. When the reactions were performed under ultrasound irradiation, the Candida antarctica lipase catalyzed reactions yielded pure indolozines, in good yields and in very short time.

A halotolerant thermostable lipase from the marine bacteriumOceanobacillussp. PUMB02 with an ability to disrupt bacterial biofilms

“…2 In addition a number of lipases have to date been isolated from both marine bacteria and marine metagenomic libraries which have novel biochemical characteristics. [20][21][22] Lipases from microorganisms are currently the focus of much interest given their large potential in a wide variety of industrial applications in the food, pharmaceutical, cosmetics, fine chemical and dairy industries amongst others coupled with their potential use in anti biofouling 8,23 and anti-biofilm strategies. 24 Following screens involving both tributyrin and olive oil plates a bacterial strain (PUMB02) with good activity was isolated, which, following phylogenetic analysis, was classified as an Oceanobacillus species.…”

The interactions between lipase and pyridinium ligands investigated by electrochemical and spectrophotometric methods

“…In the absence of enzyme an anodic current peak I a of 0.24 μA (at +0.7 V for 0.1 V s -1 ) for Lr is recorded in comparison with Lm which presents lower anodic current, of 0.14 μA (at +0.7 V). An explanation is that Lr is more electrochemical active compared to Lm, because of the structural differences, Lm having a mobile ethylenic group in its structure [9,26,27]. The anodic current peak increases with 0.25 μA and a new current peak appeared for Lr electrolyte in the presence of 0.05 mg mL -1 lipase added, in comparison with Lr without enzyme.…”

“…Pyridinium ligands have an essential role in biological systems and could be involved in cycloaddition reactions with different dipolarophiles (ethyl propiolate), in order to obtain the indolizine core using enzymes as biocatalysts. Dipolarophiles such as ethyl propiolate are important precursors used to obtain indolizines through cycloaddition reactions of quaternary pyridinium ligands with activated alkynes.Phenacyl bromide is also an important precursor involved in the biocatalytic process with lipase [9]. N-heterocyclic quaternary ligands were designed as precursors for fluorescent indolizine synthesis [10].…”

“…Commercial lipases could also be used in biocatalytic reactions to obtain indolizines [9]. Due to their eco-friendly and recyclable properties, lipases are involved in the synthesis of tricyanovinylated compounds [21] and in the design of mesoporous materials [22], green polymers [23] and bioelectrodes used to detect triglycerides in human serum [24].…”

Design and Synthesis of Novel Indolizine Analogues as COX-2 Inhibitors: Computational Perspective and in vitro Screening

“…5HT3 receptor antagonist, 38 anticholinergic, 39 anticancer, [40][41][42] estrogen receptor binding, 43 antioxidant, 44,45 antimicrobial, 46 antimutagenic, 47 CNS depressant 48 and hypoglycemic activities. 49,50 Cyclooxygenase (COX) enzyme mainly occurs in two isoforms COX-1 and COX-2 that have 60% identity of their sequence and the latter one is the key enzyme in the biosynthetic pathway leading to the development of prostaglandins, which are mediators of inflammation.…”