Phosphorylation of isoprenoid alcohols

Davisson, V. Jo; Woodside, Andrew B.; Neal, T.; Stremler, Kay E.; Muehlbacher, M.; Poulter, C. Dale

doi:10.1021/jo00375a005

Cited by 314 publications

(235 citation statements)

References 6 publications

(11 reference statements)

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“…18 The most efficient pathway to produce quantitatively 7, has been to use the Arbusov reaction according to Davisson difluorodibromomethane. 24 Furthermore, the transformation of bromodifluoromethylphosphonate 7 into nucleophilic Grignard or heterocuprate reagents and their reaction with allyl bromide were explored. Unfortunately, none of these reactions were successful to produce allyl difluoromethylphosphonate 5.…”

Section: Scheme 1 Retrosynthetic Pathwaymentioning

confidence: 99%

Preparation of gem-difluorinated retrohydroxamic-fosmidomycin

Volle¹,

Midrier²,

Blanchard³

et al. 2015

Arkivoc

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From several decades, some organophosphorus compounds specifically designed to alter biological systems were introduced on market as agrochemicals (ie glyphosate and glufosinate as herbicides). Nevertheless, it becomes necessary to find new compounds in order to counter plant resistances already observed with glyphosate. Fosmidomicyn and its N-acetyl analogues FR-900098 were perceived as starting points for elaboration of new herbicide candidates, targeting the second enzyme of the non-mevalonate pathway in plants, the 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DOXP reductoisomerase or DXR). It is expected that the enhancement of bioactivity compared to the parent compounds, might be reached by insertion of two fluorine atoms close to the phosphonate function. Indeed, the presence of both fluorine atoms could improve the lipophilicity, affect the pKa of the phosphonic acid function and then induce better activities. Herein, the synthesis of gem-difluorinated analogues of retrohydroxamic fosmidomycin and FR-900098-ester is reported using a radical addition mediated by a cobaloxime complex.

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Section: Scheme 1 Retrosynthetic Pathwaymentioning

confidence: 99%

Preparation of gem-difluorinated retrohydroxamic-fosmidomycin

Volle¹,

Midrier²,

Blanchard³

et al. 2015

Arkivoc

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“…13 Farnesyl diphosphate (FPP) was synthesized from farnesol according to the method of Poulter. 23 Primers were purchased from Integrated DNA Technologies (IDT). E. cloni Express electrocompetent E. coli BL21 (DE3) was purchased from Lucigen.…”

Section: General Proceduresmentioning

confidence: 99%

Improved selectivity of an engineered multi-product terpene synthase

et al. 2014

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Mutation of the sesquiterpene synthase Cop2 was conducted with a high-throughput screen for the cyclization activity using a non-natural substrate. A mutant of Cop2 was identified that contained three amino acid substitutions. This mutant, 17H2, converted the natural substrate FPP into germacrene D-4-ol with 77% selectivity. This selectivity is in contrast to that of the parent enzyme in which germacrene D-4-ol is produced as 29% and α-cadinol is produced as 46% of the product mixture. The mutations were shown to each contribute to this selectivity, and a homology model suggested that the mutations lie near to the active site though would be unlikely to be targeted for mutation by rational methods. Kinetic comparisons show that 17H2 maintains a k cat /K M of 0.62 mM −1 s −1 , which is nearly identical to that of the parent Cop2, which had a k cat /K M of 0.58 mM −1 s −1 .

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“…2,3 For a rational engineering of terpene cyclases, a detailed elucidation of the reaction mechanism of individual cyclases is essential. Conventionally, whole cell-incorporation experiments of simple isotopically labeled precursors, such as doubly 13 C-and 2 H-labeled sodium acetate and mevalonolactone, are used to study the cyclization pathways. 4 In vitro analysis of terpene cyclases with specifically isotope-labeled precursors is a more straightforward method for elucidating their mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Cyclization mechanism of phomopsene synthase: mass spectrometry based analysis of various site-specifically labeled terpenes

et al. 2017

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Elucidation of the cyclization mechanism catalyzed by terpene synthases is important for the rational engineering of terpene cyclases. We developed a chemoenzymatic method for the synthesis of systematically deuterium-labeled geranylgeranyl diphosphate (GGPP), starting from site-specifically deuterium-labeled isopentenyl diphosphates (IPPs) using IPP isomerase and three prenyltransferases. We examined the cyclization mechanism of tetracyclic diterpene phomopsene with phomopsene synthase. A detailed EI-MS analysis of phomopsene labeled at various positions allowed us to propose the structures corresponding to the most intense peaks, and thus elucidate a cyclization mechanism involving double 1,2-alkyl shifts and a 1,2-hydride shift via a dolabelladien-15-yl cation. Our study demonstrated that this newly developed method is highly sensitive and provides sufficient information for a reliable assignment of the structures of fragmented ions.

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Phosphorylation of isoprenoid alcohols

Cited by 314 publications

References 6 publications

Preparation of gem-difluorinated retrohydroxamic-fosmidomycin

Preparation of gem-difluorinated retrohydroxamic-fosmidomycin

Improved selectivity of an engineered multi-product terpene synthase

Cyclization mechanism of phomopsene synthase: mass spectrometry based analysis of various site-specifically labeled terpenes

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