22488-05-7Relevant academic research and scientific papers
SYNTHESIS OF (2Z,6Z,10Z,14E,18E)-FARNESYLFARNESOL
Moiseenkov, Alexander M.,Polunin, Evgeni V.,Semenovsky, Alexei V.
, p. 3309 - 3312 (1981)
Nine-step synthesis of the title triterpenol from (E,E)-farnesol using a two-stage cis-C5-homologation procedure is described.
A general stereocontrolled, convergent synthesis of oligoprenols that parallels the biosynthetic pathway
Radetich, Branko,Corey
, p. 2430 - 2431 (2002)
A solution is reported to the classic unsolved problem of stereoselective synthesis of all-E oligoprenols, such as E-farnesylfarnesol, by a cationic coupling analogous to the biosynthetic pathway. The simplicity and efficacy of the method, which is outlined in Scheme 1, are demonstrated by the synthesis of a series of all-E oligoprenols from C20 to C35 in uniformly excellent overall yield. The success of the approach is due not only to the highly E-stereoselective C-C coupling that forms the oligoprenyl chain but also to the development of efficient syntheses of allylic secondary silanes and E-oligoprenal acetals, and to a selective allylic demethoxylation reaction. Copyright
Synergistic factors ensue high expediency in the synthesis of menaquinone [K2] analogue MK-6: Application to access an efficient one-pot protocol to MK-9
Yerramsetti, Nanaji,Dampanaboina, Lavanya,Mendu, Venugopal,Battula, Satyanarayana
, (2020/11/12)
Here we report a practical and efficient method for the synthesis of menaquinone vitamin (K2) analog MK-6 in all trans forms through “1 + 5 convergent synthetic approach” of pentaprenyl chloride with monoprenyl menadione derivative. In the synergistic factors, less efficient leaving group/more efficient nucleophile (Cl) in the substrate makes it more prominent reaction by eliminating all Sn2’ side reaction products. Further, the addition of acetic acid in the last step (desulfonation) of reaction sequence removes the limitations of the reactions in terms of cyclized side product (multiple reactions of pentaprenyl alcohol with Et3B), byproduct (Et3B, incendiary compound) formations and their interruption in the tricky purification processes. The utility of this method was further extended to find an efficient one-pot synthesis to MK-9 to the gram scale synthesis. This approach is economical and efficient and avoids the awkward chromatographic separation processes.
Biosynthesis of sesterterpenes, head-to-tail triterpenes, and sesquarterpenes in Bacillus clausii: Identification of multifunctional enzymes and analysis of isoprenoid metabolites
Ueda, Daijiro,Yamaga, Hiroaki,Murakami, Mizuki,Totsuka, Yusuke,Shinada, Tetsuro,Sato, Tsutomu
, p. 1371 - 1377 (2015/06/16)
We performed functional analysis of recombinant enzymes and analysis of isoprenoid metabolites in Bacillus clausii to gain insights into the biosynthesis of rare terpenoid groups of sesterterpenes, head-to-tail triterpenes, and sesquarterpenes. We have identified an (all-E)-isoprenyl diphosphate synthase (E-IDS) homologue as a trifunctional geranylfarnesyl diphosphate (GFPP)/hexaprenyl diphosphate (HexPP)/heptaprenyl diphosphate (HepPP) synthase. In addition, we have redefined the function of a tetraprenyl-β-curcumene synthase homologue as that of a trifunctional sesterterpene/triterpene/sesquarterpene synthase. This study has revealed that GFPP, HexPP, and HepPP, intermediates of two isoprenoid pathways (acyclic terpenes and menaquinones), are biosynthesized by one trifunctional E-IDS. In addition, GFPP/HexPP and HepPP are the primary substrates for the biosynthesis of acyclic terpenes and menaquinone-7, respectively. Multifunctional terpene biosynthetic enzymes: Geranylfarnesyl diphosphate (GFPP), hexaprenyl diphosphate (HexPP), and heptaprenyl diphosphate (HepPP) are intermediates in two isoprenoid pathways and are biosynthesized by one trifunctional (all-E)-isoprenyl diphosphate synthase. GFPP/HexPP and HepPP are mainly utilized for the biosynthesis of acyclic terpenes and menaquinone-7, respectively.
Staphylococcus aureus penicillin-binding protein 2 can use depsi-lipid ii derived from vancomycin-resistant strains for cell wall synthesis
Nakamura, Jun,Yamashiro, Hidenori,Miya, Hiroto,Nishiguchi, Kenzo,Maki, Hideki,Arimoto, Hirokazu
, p. 12104 - 12112 (2013/09/23)
Vancomycin-resistant Staphylococcus aureus (S. aureus) (VRSA) uses depsipeptide-containing modified cell-wall precursors for the biosynthesis of peptidoglycan. Transglycosylase is responsible for the polymerization of the peptidoglycan, and the penicillin-binding protein 2 (PBP2) plays a major role in the polymerization among several transglycosylases of wild-type S. aureus. However, it is unclear whether VRSA processes the depsipeptide-containing peptidoglycan precursor by using PBP2. Here, we describe the total synthesis of depsi-lipid I, a cell-wall precursor of VRSA. By using this chemistry, we prepared a depsi-lipid II analogue as substrate for a cell-free transglycosylation system. The reconstituted system revealed that the PBP2 of S. aureus is able to process a depsi-lipid II intermediate as efficiently as its normal substrate. Moreover, the system was successfully used to demonstrate the difference in the mode of action of the two antibiotics moenomycin and vancomycin. Copyright
Synthesis of a comprehensive polyprenol library for the evaluation of bacterial enzyme lipid substrate specificity
Wu, Baolin,Woodward, Robert,Wen, Liuqing,Wang, Xuan,Zhao, Guohui,Wang, Peng George
, p. 8162 - 8173 (2014/01/06)
Polyprenols, a universal class of glycan-carrier lipids, play important roles in glycan biosynthesis in wide variety of living organisms. The chemical synthesis of natural polyisoprenols such as undecaprenol and dolichols, and even more so the synthesis o
GERANYLGERANYLACETONE DERIVATIVES
-
, (2013/04/13)
Provided herein are geranylgeranylacetone derivatives and methods of using them.
Synthesis and NMR characterization of (Z, Z, Z, Z, E, E,ω)- heptaprenol
Hesek, Dusan,Lee, Mijoon,Zajicek, Jaroslav,Fisher, Jed F.,Mobashery, Shahriar
supporting information; experimental part, p. 13881 - 13888 (2012/10/08)
We describe a practical, multigram synthesis of (2Z,6Z,10Z,14Z,18E,22E)-3, 7,11,15,19,23,27-heptamethyl-2,6,10,14,18,22,26-octacosaheptaen-1-ol [(Z 4,E2,ω)-heptaprenol, 4] using the nerol-derived sulfone 8 as the key intermediate. Su
Modular synthesis of diphospholipid oligosaccharide fragments of the bacterial cell wall and their use to study the mechanism of moenomycin and other antibiotics
Gampe, Christian M.,Tsukamoto, Hirokazu,Wang, Tsung-Shing Andrew,Walker, Suzanne,Kahne, Daniel
, p. 9771 - 9778 (2012/02/15)
We present a flexible, modular route to GlcNAc-MurNAc-oligosaccharides that can be readily converted into peptidoglycan (PG) fragments to serve as reagents for the study of bacterial enzymes that are targets for antibiotics. Demonstrating the utility of these synthetic PG substrates, we show that the tetrasaccharide substrate lipid IV (3), but not the disaccharide substrate lipid II (2), significantly increases the concentration of moenomycin A required to inhibit a prototypical PG-glycosyltransferase (PGT). These results imply that lipid IV and moenomycin A bind to the same site on the enzyme. We also show the moenomycin A inhibits the formation of elongated polysaccharide product but does not affect length distribution. We conclude that moenomycin A blocks PG-strand initiation rather than elongation or chain termination. Synthetic access to diphospholipid oligosaccharides will enable further studies of bacterial cell wall synthesis with the long-term goal of identifying novel antibiotics.
Transpeptidase-mediated incorporation of d-amino acids into bacterial peptidoglycan
Lupoli, Tania J.,Tsukamoto, Hirokazu,Doud, Emma H.,Wang, Tsung-Shing Andrew,Walker, Suzanne,Kahne, Daniel
, p. 10748 - 10751 (2011/09/13)
The β-lactams are the most important class of antibiotics in clinical use. Their lethal targets are the transpeptidase domains of penicillin binding proteins (PBPs), which catalyze the cross-linking of bacterial peptidoglycan (PG) during cell wall synthesis. The transpeptidation reaction occurs in two steps, the first being formation of a covalent enzyme intermediate and the second involving attack of an amine on this intermediate. Here we use defined PG substrates to dissect the individual steps catalyzed by a purified E. coli transpeptidase. We demonstrate that this transpeptidase accepts a set of structurally diverse d-amino acid substrates and incorporates them into PG fragments. These results provide new information on donor and acceptor requirements as well as a mechanistic basis for previous observations that noncanonical d-amino acids can be introduced into the bacterial cell wall.
