4936-73-6Relevant academic research and scientific papers
Modular Chemoenzymatic Synthesis of Terpenes and their Analogues
Allemann, Rudolf K.,Benton, Jennifer C. R.,Dunbabin, Alice,Johnson, Luke A.,Mart, Robert J.
supporting information, p. 8486 - 8490 (2020/03/30)
Non-natural terpenoids offer potential as pharmaceuticals and agrochemicals. However, their chemical syntheses are often long, complex, and not easily amenable to large-scale production. Herein, we report a modular chemoenzymatic approach to synthesize terpene analogues from diphosphorylated precursors produced in quantitative yields. Through the addition of prenyl transferases, farnesyl diphosphates, (2E,6E)-FDP and (2Z,6Z)-FDP, were isolated in greater than 80 % yields. The synthesis of 14,15-dimethyl-FDP, 12-methyl-FDP, 12-hydroxy-FDP, homo-FDP, and 15-methyl-FDP was also achieved. These modified diphosphates were used with terpene synthases to produce the unnatural sesquiterpenoid semiochemicals (S)-14,15-dimethylgermacrene D and (S)-12-methylgermacrene D as well as dihydroartemisinic aldehyde. This approach is applicable to the synthesis of many non-natural terpenoids, offering a scalable route free from repeated chain extensions and capricious chemical phosphorylation reactions.
Probing the Substrate Promiscuity of Isopentenyl Phosphate Kinase as a Platform for Hemiterpene Analogue Production
Lund, Sean,Courtney, Taylor,Williams, Gavin J.
, p. 2217 - 2221 (2019/08/02)
Isoprenoids are a large class of natural products with wide-ranging applications. Synthetic biology approaches to the manufacture of isoprenoids and their new-to-nature derivatives are limited due to the provision in nature of just two hemiterpene buildin
One-pot synthesis of organophosphate monoesters from alcohols
Lira, Lucas M.,Vasilev, Dimitar,Pilli, Ronaldo A.,Wessjohann, Ludger A.
, p. 1690 - 1692 (2013/04/10)
A one-pot procedure for the phosphorylation of alcohols provides the corresponding phosphate monoesters in improved yields. The protocol features the use of tetrabutylammonium hydrogen phosphate and trichloroacetonitrile, followed by purification of the crude product by flash chromatography on silica gel. The final step, cation exchange chromatography, affords the organophosphates as ammonium salts that are usually required for biochemical applications. The mechanism appears to be phosphate rather than alcohol activation by trichloroacetonitrile.
Characterization of thermophilic archaeal isopentenyl phosphate kinases
Chen, Mo,Poulter, C. Dale
experimental part, p. 207 - 217 (2010/10/21)
Archaea synthesize isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), the essential building blocks of isoprenoid compounds, from mevalonate (MVA). However, an analysis of the genomes of several members of the Archaea failed to identify genes for the enzymes required to convert phosphomevalonate (PM) to IPP in eukaryotes. The recent discovery of an isopentenyl kinase (IPK) in Methanocaldococcus jannaschii (MJ) suggests a new variation of the MVA pathway where PM is decarboxylated to give isopentenyl phosphate (IP), which is phosphorylated to produce IPP. A blast search using the MJ protein as a probe revealed a subfamily of amino acid kinases that include the fosfomycin resistance protein fomA, which deactivates the antibiotic by phosphorylation of its phosphonate residue in a reaction similar to the conversion of IP to IPP. IPK genes were cloned from two organisms identified in the search, Methanothermobacter thermautotrophicus (MTH) and Thermoplasma acidophilum (THA), and the His-tagged recombinant proteins were purified by Ni-NTA chromatography. The enzymes catalyze the reversible phosphorylation of IP by ATP, Keq=6.3 ± 1. The catalytic efficiencies (V/K) of the proteins were ～2 × 106M-1 s-1. In the reverse direction, ADP was a substrate inhibitor for THAIPK, Ki ADP=58 ±6 μM, but not forMTHIPK. Both enzymes were active over a broad range of pH and temperature. Five compounds, dimethylallyl phosphate, isopentenyl thiolophosphate, 1-butyl phosphate, 3-buten-1-yl phosphate, and geranyl phosphate, were evaluated as alternative substrates for the MTH and THA IP kinases. All of the compounds were phosphorylated, although the catalytic efficiency was low for geranyl phosphate. 2009 American Chemical Society.
Mono, di and tri-mannopyranosyl phosphates as mannose-1-phosphate prodrugs for potential CDG-Ia therapy
Hardre, Renaud,Khaled, Amira,Willemetz, Alexandra,Dupre, Thierry,Moore, Stuart,Gravier-Pelletier, Christine,Merrer, Yves Le
, p. 152 - 155 (2007/10/03)
An efficient and convergent method for the synthesis of mannose-1-phosphate prodrugs is described as a potential therapy for congenital disorders of glycosylation-Ia (CDG-Ia). The key feature of the proposed approach is the silver assisted nucleophilic substitution of 2,3,4,6-tetra-O-protected-α-d-mannopyranosyl bromides with various silver phosphate salts to afford mono, di, and tri-mannopyranosyl phosphates. A preliminary biological evaluation of the synthesized phosphate prodrugs has been carried out.
On the influence of phosphoric ester groups in geranyldiphosphate biosynthesis
Jacob, L.,Julia, M.,Pfeiffer, B.,Rolando, C.
, p. 719 - 733 (2007/10/02)
Elimination reactions have been performed on sulfonium salts mimicking the intermediates in the title reaction.It has been found that the direction of the elimination is strongly influenced by the phosphate residue favouring the formation of the "natural" isomer.This has been attributed to the very strong electron attracting power of the phosphoric ester group.Keywords: prenyl transferase / phosphoric esters / orientation of elimination reactions
