35289-31-7Relevant academic research and scientific papers
Chemoenzymatic macrocycle synthesis using resorcylic acid lactone thioesterase domains
Heberlig, Graham W.,Brown, Jesse T. C.,Simard, Ryan D.,Wirz, Monica,Zhang, Wei,Wang, Meng,Susser, Leah I.,Horsman, Mark E.,Boddy, Christopher N.
, p. 5771 - 5779 (2018)
A key missing tool in the chemist's toolbox is an effective biocatalyst for macrocyclization. Macrocycles limit the conformational flexibility of small molecules, often improving their ability to bind selectively and with high affinity to a target, making them a privileged structure in drug discovery. Macrocyclic natural product biosynthesis offers an obvious starting point for biocatalyst discovery via the native macrocycle forming biosynthetic mechanism. Herein we demonstrate that the thioesterase domains (TEs) responsible for macrocyclization of resorcylic acid lactones are promising catalysts for the chemoenzymatic synthesis of 12- to 18-member ring macrolactones and macrolactams. The TE domains responsible for zearalenone and radicicol biosynthesis successfully generate resorcylate-like 12- to 18-member macrolactones and a 14-member macrolactam. In addition these enzymes can also macrolactonize a non-resorcylate containing depsipeptide, suggesting they are versatile biocatalysts. Simple saturated omega-hydroxy acyl chains are not macrocyclized, nor are the alpha-beta unsaturated derivatives, clearly outlining the scope of the substrate tolerance. These data dramatically expand our understanding of substrate tolerance of these enzymes and are consistent with our understanding of the role of TEs in iterative polyketide biosynthesis. In addition this work shows these TEs to be the most substrate tolerant polyketide macrocyclizing enzymes known, accessing resorcylate lactone and lactams as well as cyclicdepsipeptides, which are highly biologically relevant frameworks.
Synthesis of γ,δ-unsaturated-β-keto lactones via sequential cross metathesis-lactonization: A facile entry to macrolide antibiotic (-)-A26771B
Gebauer, Julian,Blechert, Siegfried
, p. 2021 - 2025 (2006)
A simple access to γ,δ-unsaturated-β-keto lactones is presented, allowing a rapid total synthesis of the naturally occurring 16-membered macrolide antibiotic (-)-A26771B via cross metathesis, asymmetric dihydroxylation, and lactonization as the key steps.
4,4,16-Trifluoropalmitate: Design, Synthesis, Tritiation, Radiofluorination and Preclinical PET Imaging Studies on Myocardial Fatty Acid Oxidation
Colombano, Alessandro,Dall'Angelo, Sergio,Kingston, Lee,Gr?nberg, Gunnar,Correia, Claudia,Passannante, Rossana,Baz, Zuri?e,Morcillo, Miguel ángel,Elmore, Charles S.,Llop, Jordi,Zanda, Matteo
, p. 2317 - 2331 (2020/10/02)
Fatty acid oxidation (FAO) produces most of the ATP used to sustain the cardiac contractile work, although glycolysis is a secondary source of ATP under normal physiological conditions. FAO impairment has been reported in the advanced stages of heart failure (HF) and is strongly linked to disease progression and severity. Thus, from a clinical perspective, FAO dysregulation provides prognostic value for HF progression, the assessment of which could be used to improve patient monitoring and the effectiveness of therapy. Positron emission tomography (PET) imaging represents a powerful tool for the assessment and quantification of metabolic pathways in vivo. Several FAO PET tracers have been reported in the literature, but none of them is in routine clinical use yet. Metabolically trapped tracers are particularly interesting because they undergo FAO to generate a radioactive metabolite that is subsequently trapped in the mitochondria, thus providing a quantitative means of measuring FAO in vivo. Herein, we describe the design, synthesis, tritium labelling and radiofluorination of 4,4,16-trifluoro-palmitate (1) as a novel potential metabolically trapped FAO tracer. Preliminary PET-CT studies on [18F]1 in rats showed rapid blood clearance, good metabolic stability – confirmed by using [3H]1 in vitro – and resistance towards defluorination. However, cardiac uptake in rats was modest (0.24±0.04 % ID/g), and kinetic analysis showed reversible uptake, thus indicating that [18F]1 is not irreversibly trapped.
SYNTHESIS OF STRAIGHT-CHAIN LEPIDOPTERAN PHEROMONES THROUGH ONE- OR TWO- CARBON HOMOLOGATION OF FATTY ALKENES
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, (2020/02/14)
Methods for the preparation of alkenes including insect pheromones are described. The methods include homologation reactions employing reagents such as 1,3-diesters, epoxides, cyanoacetates, and cyanide salts for elongation of starting materials and intermediates by one or two carbon atoms. The alkenes include insect pheromones useful in a number of agricultural applications.
Quantitative Evaluation of the Effect of the Hydrophobicity of the Environment Surrounding Br?nsted Acid Sites on Their Catalytic Activity for the Hydrolysis of Organic Molecules
Miura, Hiroki,Kameyama, Shutaro,Komori, Daiki,Shishido, Tetsuya
, p. 1636 - 1645 (2019/01/21)
Sulfo-functionalized siloxane gels with a variety of surface hydrophobicities were fabricated to elucidate the effect of the environment surrounding the Br?nsted acid site on their catalytic activity for the hydrolysis of organic molecules. A detailed structural analysis of these siloxane gels by elemental analysis, X-ray photoelectron spectroscopy, Fourier-transformed infrared (FT-IR), and 29Si MAS NMR revealed the formation of gel catalysts with a highly condensed siloxane network, which enabled us to quantitatively evaluate the hydrophobicity of the environment surrounding the catalytically active sulfo-functionality. A sulfo group in a highly hydrophobic environment exhibited excellent catalytic turnover frequency for the hydrolysis of acetate esters with a long alkyl chain, whereas not only conventional solid acid catalysts but also liquid acids showed quite low catalytic activity. Detailed kinetic studies corroborated that the adsorption of oleophilic esters at the Br?nsted acid site was facilitated by the surrounding hydrophobic environment, thus significantly promoting hydrolysis under aqueous conditions. Furthermore, sulfo-functionalized siloxane gels with a highly hydrophobic surface showed excellent catalytic activity for the hydrolytic deprotection of silyl ethers.
Ring-Closing Metathesis with Vicinal Dibromoalkenes as Protected Alkynes: A Synthetic Approach to Macrocyclic Enynes
Karabiyikoglu, Sedef,Iafe, Robert G.,Merlic, Craig A.
, p. 5248 - 5251 (2015/11/18)
A new strategy to access macrocyclic enynes was developed. To block undesired ene-yne cyclization pathways, alkynes were protected via bromination and the resultant acyclic vic-(E)-dibromotrienes participated in selective ene-ene ring closing metathesis reactions. Zinc-promoted deprotection of (E)-dibromodienes provided macrocyclic enynes in high yields.
SYNTHESIS OF OLEFINIC ALCOHOLS VIA ENZYMATIC TERMINAL HYDROXYLATION
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Paragraph 0299; 0301, (2016/01/30)
In certain aspects, the present invention provides methods for producing terminally hydroxylated alkenes and alkynes by contacting an unsaturated or saturated hydrocarbon substrate with a hydroxylase enzyme. Exemplary terminal hydroxylases useful for carrying out the methods of the invention exhibit strong selectivity towards one terminal carbon of a hydrocarbon substrate and include, but are not limited to, non-heme diiron alkane monooxygenases, cytochromes P450 (e.g., cytochromes P450 of the CYP52 and CYP153 family), as well as long chain alkane hydroxylases. In some embodiments, the terminally hydroxylated alkene or alkyne is further converted to a terminal alkenal. In certain embodiments, terminally hydroxylated alkenes and alkynes are useful as insect pheromones which modify insect behavior. In other embodiments, terminally hydroxylated alkenes and alkynes are useful intermediates for producing pheromones via acetylation or oxidation of the alcohol moiety.
One-Carbon Homologation of Primary Alcohols and the Reductive Homologation of Aldehydes Involving a Jocic-Type Reaction
Li, Zhexi,Gupta, Manoj K.,Snowden, Timothy S.
, p. 7009 - 7019 (2015/11/16)
(Trichloromethyl)carbinols, which are formed in one operation from either alcohols or aldehydes, can be converted into primary alcohols in a Jocic-type reaction involving LiBH4. The net result is a convenient two-step, one-carbon homologation of primary alcohols or a reductive one-carbon homologation of aldehydes featuring a broad substrate scope. The method is step-economical, and it nicely complements established one-carbon homologation strategies. (Trichloromethyl)carbinols, which are formed in one operation from either alcohols or aldehydes, can be converted into primary alcohols in a Jocic-type reaction involving LiBH4. The net result is a convenient two-step, one-carbon homologation of primary alcohols or a reductive one-carbon homologation of aldehydes featuring a broad substrate scope.
A facile asymmetric synthesis of (S)-14-methyl-1-octadecene, the sex pheromone of the peach leafminer moth
Zhang, Tao,Ma, Wei-Li,Li, Tian-Rui,Wu, Jia,Wang, Jun-Run,Du, Zhen-Ting
, p. 5201 - 5208 (2013/06/27)
An asymmetric synthesis of 14-methyl-1-octadecene, the sex pheromone of the peach leafminer moth has been achieved. The target molecule was synthesized in six linear steps and in 30.3% overall yield from commercially available hexanoyl chloride, (S)-4-benzyloxazolidin-2-one and 1,9-nonanediol. The hexanoyl chloride was connected with (S)-4-benzyloxazolidin-2-one, and with the induction of the chiral oxazolidinone auxiliary, after chiral methylation, LAH reduction and then tosylation gave the chiral key intermediate 5 in high stereoselectivity. 1,9-Nonanediol, was selectively brominated, THP protected and subjected to Li2CuCl4-mediated C-C coupling to afford a C12 intermediate. The target molecule, (S)-14-methyl-1-octadecene, was obtained after the two parts were subjected to a second Li 2CuCl4-mediated C-C coupling. Our synthetic approach represents the first time a substrate-control asymmetric synthesis of (S)-14-methyl-1-octadecene has been reported.
An organocatalytic enantioselective synthesis of (+)-duryne
Kumaraswamy, Gullapalli,Sadaiah, Kadivendi,Raghu, Nimmakayala
, p. 587 - 593 (2012/08/13)
An efficient enantioselective synthesis of the potent anticancer agent (+)-duryne was achieved by the use of a one-pot organocatalyzed hydroxylation/Ohira-Bestmann and Grubbs cross-metathesis/selective cis-Wittig reaction. This new approach is envisioned to facilitate the synthesis of every representative member of the family.
