Structural Analysis ofPseudomonas1-Aminocyclopropane-1-carboxylate Deaminase Complexes:  Insight into the Mechanism of a Unique Pyridoxal-5‘-phosphate Dependent Cyclopropane Ring-Opening Reaction†,‡

Biochemistry ◽  
2004 ◽  
Vol 43 (42) ◽  
pp. 13328-13339 ◽  
Author(s):  
Subramanian Karthikeyan ◽  
Qingxian Zhou ◽  
Zongbao Zhao ◽  
Chai-Lin Kao ◽  
Zhihua Tao ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Ring Opening ◽  
Cyclopropane Ring ◽  
Ring Opening Reaction ◽  
Insight Into

One-Step Synthesis of Heteroaromatic-Fused Pyrrolidines via Cyclopropane Ring-Opening Reaction:  Application to the PKCβ Inhibitor JTT-010

2007 ◽  
Vol 9 (17) ◽  
pp. 3331-3334 ◽  
Author(s):  
Masahiro Tanaka ◽  
Minoru Ubukata ◽  
Takafumi Matsuo ◽  
Katsutaka Yasue ◽  
Katsuya Matsumoto ◽  
...  
Keyword(s):  
Ring Opening ◽  
Cyclopropane Ring ◽  
Ring Opening Reaction ◽  
One Step

Synthesis of N-isobutylnoroxymorphone from naltrexone by a selective cyclopropane ring opening reaction

2008 ◽  
Vol 18 (18) ◽  
pp. 4978-4981 ◽  
Author(s):  
Hideaki Fujii ◽  
Yumiko Osa ◽  
Marina Ishihara ◽  
Shinichi Hanamura ◽  
Toru Nemoto ◽  
...  
Keyword(s):  
Ring Opening ◽  
Cyclopropane Ring ◽  
Ring Opening Reaction

ChemInform Abstract: Synthesis of N-Isobutylnoroxymorphone from Naltrexone by a Selective Cyclopropane Ring Opening Reaction.

ChemInform ◽  
2009 ◽  
Vol 40 (5) ◽  
Author(s):  
Hideaki Fujii ◽  
Yumiko Osa ◽  
Marina Ishihara ◽  
Shinichi Hanamura ◽  
Toru Nemoto ◽  
...  
Keyword(s):  
Ring Opening ◽  
Cyclopropane Ring ◽  
Ring Opening Reaction

ChemInform Abstract: One-Step Synthesis of Heteroaromatic-Fused Pyrrolidines via Cyclopropane Ring-Opening Reaction: Application to the PKCβ Inhibitor JTT-010.

ChemInform ◽  
2008 ◽  
Vol 39 (1) ◽  
Author(s):  
Masahiro Tanaka ◽  
Minoru Ubukata ◽  
Takafumi Matsuo ◽  
Katsutaka Yasue ◽  
Katsuya Matsumoto ◽  
...  
Keyword(s):  
Ring Opening ◽  
Cyclopropane Ring ◽  
Ring Opening Reaction ◽  
One Step

Asymmetric Synthesis of Protected 2-Substituted Cyclopropane Amino Acids

1998 ◽  
Vol 51 (2) ◽  
pp. 127 ◽  
Author(s):  
Stephen G. Pyne ◽  
Karl Schafer ◽  
Brian W. Skelton ◽  
Allan H. White
Keyword(s):  
Amino Acids ◽  
Structural Analysis ◽  
Single Crystal ◽  
Asymmetric Synthesis ◽  
Acid Hydrolysis ◽  
Sodium Borohydride ◽  
Ring Opening ◽  
Cyclopropane Ring ◽  
X Ray ◽  
Sulfur Ylide

The cyclopropanation reactions of (1a) with ethyl and t-butyl (dimethylsulfuranylidene)acetate proceeded with good diastereoselectivity and resulted in the formation of three diastereoisomeric products. The major diastereoisomeric product ((2a) and (2b), respectively) could be isolated in pure form by simple recrystallization. The stereochemistry of the major cyclopropane product (2b) has been determined by single-crystal X-ray structural analysis. These cyclopropanation products were susceptible to ring opening of the cyclopropane ring upon reduction with sodium borohydride or acid hydrolysis. The reaction of (1b) with ethyl (dimethylsulfuranylidene)acetate gave a mixture of four diastereoisomeric cyclopropanation products. The reactions of (1a) and (1b) with the sulfur ylide derived from 3-methoxycarbonylallyldimethylsulfonium bromide were less successful in terms of product diastereoselectivities.

scholarly journals Identifying the Mechanism of Action of Bioactive 1,2-Cyclopropyl Carbohydrates

2021 ◽  
Author(s):  
◽  
Loïc Lassueur
Keyword(s):  
Mechanism Of Action ◽  
Ring Opening ◽  
Cyclopropane Ring ◽  
Affinity Purification ◽  
Potential Mechanism ◽  
Chemical Genetic ◽  
Mechanism Of Inhibition ◽  
Ring Opening Reaction ◽  
Rhodium Acetate ◽  
Protein Localisation

<p>Cyclopropanes and carbohydrates have long been used in the field of drug development. Previous work has shown that 1,2-cyclopropyl carbohydrates display bioactivity in both HeLa cancer cell lines¹ and in yeast² with a tentatively proposed mechanism of inhibition occurring through an enzymatic cyclopropane ring opening reaction and subsequent formation of a covalent bond with a target enzyme.²  A small library of 1,2-cyclopropyl carbohydrate derivatives were synthesised based on known pharmacophores to examine further the potential mechanism of inhibition of such compounds and confirm the occurrence of enzyme-catalysed cyclopropane ring-opening reactions. Initial synthetic efforts were focused on the synthesis of the 1,2-dichlorocyclopropyl carbohydrate 23, which, through the optimisation of an essential C-6 detritylation reaction, was achieved in moderate yields of 32% over 7 steps. Following this, the ethoxycarbonyl substituted 1,2-cyclopropyl carbohydrate 54 was synthesised over 7 steps in a 22% yield through a rhodium acetate-catalysed addition of ethyl diazoacetate (49) to the glucal substrate 40. It was envisioned that if enzymatic cyclopropane ring-opening was occurring to form a C-7 carbanion, this would in turn be stabilised through the potential enolate formation of 54. Use of N,N-ditosylhydrazine in the synthesis of propargyl diazoacetate (58) followed by a rhodium acetate-catalysed cyclopropanation of 58 with substrate 40 resulted in the successful synthesis of 61 over 7 steps in a total yield of 9%. The incorporation of the propargyl substituent in 61 was introduced as a molecular probe in an attempt to isolate the target protein through an affinity purification procedure. The bioactivity of the propargyl derivative 61 was consistent with the synthesised compounds 23 and 54. It was proposed that these compounds undergo an enzymatic cyclopropane ring opening reaction accompanied with a clear diastereoselective preference for the α-stereoisomer of the cyclopropane ring, consistent with a target-based activation of the compounds.  Chemical genetic analysis of the resulting bioactive compounds was undertaken using a deletion mutant array of Saccharomyces cerevisiae to elucidate a potential mechanism of action. Analysis of the results showed that, of the 4800 homozygous deletion strains tested in the high-throughput screens, a total of 122 strains were found following validation to sensitise and 68 to give resistance against 23 and 54. These sensitive and resistant mutants were subjected to a validation assay. Following validation, genes whose deletion led to sensitivity or resistance were then subjected to gene ontology term enrichment analysis which showed enrichment in the cytosolic ribosome, SNARE complex and SNAP receptor activity for resistant strains and enrichment in endoplasmic reticulum and endomembrane systems was found for the sensitive strain. Genes whose deletion sensitised to both compounds showed strong enrichment in cellular protein localisation, intra-golgi vesicale-mediated transport and the endomembrane system.   Target identification and isolation were attempted through an affinity purification procedure using compound 61 and an azide-modified agarose resin. However, this was without success, either through inaccessibility of the alkyne of the target probe or because the target resides in the membrane-associated fraction which was discarded prior to treatment with the probe.   This study suggests that the 1,2-cyclopropyl carbohydrates synthesised function through a cyclopropane ring-opening reaction, assisted by an enzymatic nucleophile. Chemical genetic analysis showed that the target of these compounds is involved in protein transport and protein localisation most likely relating to the vesicle tethering. Although many aspects of this work still need further investigation, either through the synthesis of new 1,2-cyclopropyl carbohydrates to increase bioactivity and better understand the enzymatic target, or through further biological procedures to better understand the mechanism of action, the use of 1,2-cyclopropyl carbohydrates as a potential pharmaceuticals or probes of protein trafficking shows much promise.</p>

On the Conrotatory Ring Opening of 3-Carbomethoxycyclobutene Vis-À-Vis 3-Carbomethoxy-1,2-Benzocyclobutene and the Predominant Inward Opening of 3-Dimethylaminocarbonyl-1,2-Benzocyclobutene

2018 ◽  
Author(s):  
Veejendra Yadav ◽  
Dasari L V K Prasad ◽  
Arpita Yadav ◽  
Maddali L N Rao
Keyword(s):  
Transition State ◽  
Ring Opening ◽  
Electron Process ◽  
Ring Opening Reaction ◽  
Stable Species ◽  
Electron Event

<p>The torquoselectivity of conrotatory ring opening of 3-carbomethoxycyclobutene is controlled by p<sub>C1C2</sub>→s*<sub>C3C4</sub> and s<sub>C3C4</sub>→p*<sub>CO</sub> interactions in the transition state in a 4-electron process as opposed to only s<sub>C3C4</sub>→p*<sub>CO</sub> interaction in an apparently 8-electron event in 3-carbomethoxy-1,2-benzocyclobutene. The ring opening of 3-carbomethoxy-1,2-benzocyclobutene is sufficiently endothermic. We therefore argue that the reverse ring closing reaction is faster than the forward ring opening reaction and, thus, it establishes an equilibrium between the two and subsequently allows formation of the more stable species <i>via</i> outward ring opening reaction. Application of this argument to 3-dimethylaminocarbonyl-1,2-benzocyclobutene explains the predominantly observed inward opening.</p>

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