Studies Towards the Synthesis of the Core of Endiandric Acid H
In the presence of a CuBr·SMe2 catalytic system, a very simple and efficient approach for the synthesis of the key precursor of the core of endiandric acids starting from the readily and abundantly available 3-butyn-1-ol in five linear steps with an overall yield of 40% was developed.
Synthesis and biological evaluation of calycanthaceous alkaloid analogs.
Starting from 9-methyl-1,2,3,4,9,9a-hexahydro-4aH-pyrido[2,3-b]indol-4a-ol, or indole-3-acetonitrile, 40 new calycanthaceous alkaloid analogs were synthesized in excellent yields. The prepared compounds were evaluated for biological activity against acetylcholinesterase and a broad range of plant pathogen fungi. The results of bioassays indicated that the majority of tested compounds displayed comparable or better in vitro bioactivity than the positive control. Notably, compounds b8 and b9 showed higher activity against Verticillium dahlia than chlorothalonil, with MIC values of 62.5 and 7.81 µg mL-1, respectively. Compound b3 had a higher activity against Bacillus cereus, with a MIC value of 15.63 µg mL-1. Compounds c2 and c11 revealed potent activity against acetylcholinesterase, with MIC values of 0.01 and 0.1 ng mL-1, respectively. Analysis of the molecular docking modes of c2 and c11 with Torpedo californica acetylcholinesterase indicated a medium strong hydrogen bond interaction between the hydroxyl groups of both the ligands and the phenolic hydroxyl of Try121 at a distance of approximately 2.4 Å. The results obtained in this study will be useful for the further design and structural optimization of calycanthaceous alkaloids as potential agrochemical lead compounds for plant disease control.
New Trends in Fungal Biooxidation
Biooxidations using isolated biocatalysts for the oxidative conversion of organic compounds and materials are becoming more and more important in the industrial sector. Research in this direction is part of the rapidly developing field of White Biotechnology and is carried out not least against the background of sustainable development and the need to replace environmentally risky technologies by eco-friendly processes. Whereas whole cells are already widely used as oxidative biocatalysts, the application of isolated enzymes is still limited to a few examples. One reason for that is the cost-intensive production and laborious purification of enzymes which are mostly intracellular and sometimes membrane-bound proteins with low stability and complex co-factor requirements. The use of secreted oxidoreductases offers several advantages: they are easier to separate and purify, need only cheap co-substrates such as dioxygen or peroxides and are far more stable than intracellular enzymes. Filamentous fungi secrete a broad spectrum of oxidative biocatalysts which are involved, amongst others, in the degradation of recalcitrant biopolymers, the synthesis of melanins as well as the detoxification of plant ingredients, microbial metabolites and organopollutants. We focus here on novel secreted enzymes - peroxygenases and DyP-type peroxidases - with remarkable catalytic properties. Furthermore selected features of “classic” fungal oxidoreductases, such as laccase, tyrosinase and chloroperoxidase, are discussed against the background of innovative recent developments in the field of enzyme application.