6784-45-8Relevant academic research and scientific papers
Characterization of the first naturally thermostable terpene synthases and development of strategies to improve thermostability in this family of enzymes
Styles, Matthew Q.,Nesbitt, Edward A.,Marr, Scott,Hutchby, Marc,Leak, David J.
, p. 1700 - 1711 (2017)
The terpenoid family of natural products is being targeted for heterologous microbial production as a cheaper and more reliable alternative to extraction from plants. The key enzyme responsible for diversification of terpene structure is the class-I terpene synthase (TS), and these often require engineering to improve properties such as thermostability, robustness and catalytic activity before they are suitable for industrial use. Improving thermostability typically relies on screening a large number of mutants, as there are no naturally thermostable TSs described upon which to base rational design decisions. We have characterized the first examples of natural TSs exhibiting thermostability, which catalyse the formation of the sesquiterpene τ-muurolol at temperatures up to 78 °C. We also report an enzyme with a kcat value of 0.95 s?1 at 65 °C, the highest kcat recorded for a bacterial sesquiterpene synthase. In turn, these thermostable enzymes were used as a model to inform the rational engineering of another TS, with the same specificity but low sequence identity to the model. The newly engineered variant displayed increased thermostability and turnover. Given the high structural homology of the class-I TS domain, this approach could be generally applicable to improving the properties of other enzymes in this class. Database: Model data are available in the PMDB database under the accession number PM0080780.
Concise synthesis of the tetracyclic framework of azadiradione: Tandem radical cyclization route
Yamashita, Shuji,Naruko, Akito,Yamada, Takahiro,Hayashi, Yujiro,Hirama, Masahiro
, p. 220 - 221 (2013)
Azadiradione, a limonoid isolated from the neem plant, possesses a unique stereostructure distinct from that of the steroids. We describe a concise synthesis of the tetracyclic framework of azadiradione by a tandem radical cyclization process.
A mild method for the replacement of a hydroxyl group by halogen: 3. the dichotomous behavior of α-haloenamines towards allylic and propargylic alcohols
Munyemana, Fran?ois,Patiny, Luc,Ghosez, Léon
, (2021/06/07)
A study of the deoxyhalogenation of allylic and propargylic alcohols with tetramethyl-α-halo-enamines is reported. Primary allylic and primary and secondary propargylic alcohols gave the corresponding halides in high yields. Secondary allylic and propargylic alcohols yielded the corresponding secondary halides but the reaction also produced some rearranged primary halides (I > Br > Cl). The reactions with tertiary allylic and tertiary propargylic alcohols gave several products and was therefore of little synthetic value. However, the addition of triethylamine to the reaction mixture or the use of lithium alkoxide instead of alcohol brought about a major change of the course of the reaction which led to amides carrying an allyl or an allenyl group at C2. This was shown to result from a Claisen-Eschenmoser rearrangement of an intermediate α-allyloxy- or propargyloxy-enamine.
Characterization of a Sesquiterpene Synthase Catalyzing Formation of Cedrol and Two Diastereoisomers of Tricho-Acorenol from Euphorbia fischeriana
Zhu, Jianxun,Liu, Lihong,Wu, Maobo,Xia, Guiyang,Lin, Pengcheng,Zi, Jiachen
, p. 1780 - 1786 (2021/06/21)
A sesquiterpene synthase gene was identified from the transcriptome of Euphorbia fischeriana Steud, and the function of its product EfTPS12 was characterized by in vitro biochemical experiments and synthetic biology approaches. EfTPS12 catalyzed conversion of farnesyl diphosphate into three products, including cedrol (1) and eupho-Acorenols A (2) and B (3) (two diastereoisomers of tricho-Acorenol), thereby being named EfCAS herein. The structures of 2 and 3 were determined by spectroscopic methods and comparison of experimental and calculated electronic circular dichroism spectra. EfCAS is the first example of a plant-derived sesquiterpene synthase that is capable of synthesizing acorane-Type alcohols. This study also documents that synthetic biology approaches enable large-scale preparation of volatile terpenes and thereby substantially facilitate characterization of corresponding terpene synthases and elucidation of the structures of their products.
SYNTHESIS OF E,E-FARNESOL, FARNESYL ACETATE AND SQUALENE FROM FARNESENE VIA FARNESYL CHLORIDE
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, (2019/12/28)
The present disclosure provides methods for preparing polyunsaturated hydrocarbons, such as E,E-farnesol, farnesyl acetate and squalene, by base catalyzed addition of a dialkylamine to a 3-methylene-1-alkene, such as farnesene. The present disclosure also provides compositions including one more farnesene derivatives prepared using the disclosed methods.
Repositioning Salirasib as a new antimalarial agent
Porta, Exequiel O. J.,Bofill Verdaguer, Ignasi,Perez, Consuelo,Banchio, Claudia,Ferreira De Azevedo, Mauro,Katzin, Alejandro M.,Labadie, Guillermo R.
, p. 1599 - 1605 (2019/09/30)
Malaria is a serious tropical disease that kills thousands of people every year, mainly in Africa, due to Plasmodium falciparum infections. Salirasib is a promising cancer drug candidate that interferes with the post-translational modification of Ras. This S-farnesyl thiosalicylate inhibits isoprenylcysteine carboxyl methyltransferase (ICMT), a validated target for cancer drug development. There is a high homology between the human and the parasite enzyme isoforms, in addition to being a druggable target. Looking to repurpose its structure as an antimalarial drug, a collection of S-substituted derivatives of thiosalicylic acid were prepared by introducing 1,2,3-triazole as a diversity entry point or by direct alkylation of the thiol. We further investigated the in vitro toxicity of FTS analogues to Plasmodium falciparum in the asexual stages and in Vero cells. An antiplasmodial activity assay was performed using a simple, high-sensitivity methodology based on nanoluciferase (NLuc)-transfected P. falciparum parasites. The results showed that some of the analogs were active at low micromolar concentration, including Salirasib. The most potent member of the series has S-farnesyl and the 1,2,3-triazole moiety substituted with phytyl. However, the compound substituted with methyl-naphthyl shows promising physicochemical and activity values. The low cytotoxicity in eukaryotic cells of the most active analogs provided good therapeutic indices, being starting-point candidates for future antimalarial drug development.
Concise synthesis of artemisinin from a farnesyl diphosphate analogue
Tang, Xiaoping,Demiray, Melodi,Wirth, Thomas,Allemann, Rudolf K.
, p. 1314 - 1319 (2017/09/30)
Artemisinin is one of the most potent anti-malaria drugs and many often-lengthy routes have been developed for its synthesis. Amorphadiene synthase, a key enzyme in the biosynthetic pathway of artemisinin, is able to convert an oxygenated farnesyl diphosphate analogue directly to dihydroartemisinic aldehyde, which can be converted to artemisinin in only four chemical steps, resulting in an efficient synthetic route to the anti-malaria drug.
Optimising Terpene Synthesis with Flow Biocatalysis
Tang, Xiaoping,Allemann, Rudolf K.,Wirth, Thomas
supporting information, p. 414 - 418 (2017/01/24)
Sesquiterpenes are an important family of natural products, many of which exhibit important pharmaceutical and agricultural properties. They are biosynthesised from farnesyl diphosphate in sesquiterpene synthase catalysed reactions. Here, we report the development of a highly efficient segmented flow system for the enzyme-catalysed continuous flow production of sesquiterpenes. Design of experiment (DoE) methods were used to optimise the performance of the flow biocatalysis, and quantitative yields were achieved by using an operationally simple but highly effective segmented flow system.
ADHESION PREVENTING AGENT
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Paragraph 0372; 0373, (2016/04/20)
The present invention relates to an adhesion preventing agent comprising an amphipathic compound having the following general formula (I): wherein X and Y each denotes a hydrogen atom or together denote an oxygen atom, n denotes an integer from 0 to 2, m denotes the integer 1 or 2, AA: AA denotes a single bond or double bond, and R denotes a hydrophilic group having two or more hydroxyl groups.
ADHESION PREVENTING AGENT
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Paragraph 0211-0212, (2016/12/01)
PROBLEM TO BE SOLVED: To provide a compound available as an easily applicable adhesion preventing agent. SOLUTION: The invention provides an amphipathic compound represented by the general formula (II) in the figure. (In the formula, X and Y either each denote a hydrogen atom or together denote an oxygen atom, n denotes an integer from 0 to 2, m denotes the integer 1 or 2, and R denotes a hydrophilic group obtained by removal of one hydroxyl group from any one selected from the group consisting of glycerol, erythritol, pentaerythritol, diglycerol, and glyceric acid.) SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT
