scholarly journals Further Insight into Polycyclization Cascades of Acyclic Geranylfarnesol and its Acetate by Squalene-hopene Cyclase from Alicyclobacillus Acidocaldarius

2016 ◽  
Vol 11 (2) ◽  
pp. 1934578X1601100
Author(s):  
Jun Cheng ◽  
Chiaki Nakano ◽  
Guang Lu Shi ◽  
Tsutomu Hoshino
Keyword(s):  
Double Bond ◽  
Enzymatic Reaction ◽  
High Yield ◽  
Enzymatic Reactions ◽  
Terminal Double Bond ◽  
Tricyclic Compounds ◽  
Acetyl Group ◽  
Alicyclobacillus Acidocaldarius ◽  
Insight Into

The enzymatic reactions of geranylfarnesol (8) and its acetate 9, classified as sesterterpenes (C25), using squalene-hopene cyclase (SHC) were investigated. The enzymatic reaction of 8 afforded 6/6-fused bicyclic 20, 6/6/6-fused tricyclic 21, and 6/6/6/6-fused tetracyclic compounds 22 and 23 as the main products (35% yield), whereas that of 9 afforded two 6/6/6-fused tricyclic compounds 24 and 25 in a high yield (76.3%) and a small amount (5.0%) of 26 (the acetate of 22). A significantly higher conversion of 9 indicates that the arrangement of the substrate in the reaction cavity changed. The lipophilic nature and/or the bulkiness of the acetyl group may have changed its binding with SHC, thus placing the terminal double bond of 9 in the vicinity of the DXDD motif of SHC, which is responsible for the proton attack on the double bond to initiate the polycyclization reaction. The results obtained for 8 are different to some extent than those reported by Shinozaki et al. The products obtained in this study were deprotonated compounds; however, the products reported by Shinozaki et al. were hydroxylated compounds.

Regioselective Diboron-Mediated Semireduction of Terminal Allenes

Synthesis ◽  
2019 ◽  
Vol 51 (24) ◽  
pp. 4619-4624
Author(s):  
Ashley M. Gates ◽  
Webster L. Santos
Keyword(s):  
Double Bond ◽  
Palladium Catalyst ◽  
High Yield ◽  
Terminal Double Bond

A method for the regioselective reduction of the terminal double bond of 1,1-disubstituted allenes has been developed. In the presence of a palladium catalyst, tetrahydroxydiboron and stoichiometric water, allene semireduction proceeds in high yield to afford Z-alkenes selectively.

scholarly journals Synthesis of [1,4]Oxathiepino[5,6-b]quinolines via Base-Mediated Intramolecular Hydroalkoxylation

SynOpen ◽  
2022 ◽  
Vol 06 (01) ◽  
pp. 7-10
Author(s):  
Morteza Shiri ◽  
Maryam-Sadat Tonekaboni ◽  
Zahra Tanbakouchian ◽  
Soma Majedi
Keyword(s):  
Double Bond ◽  
Hydroxyl Group ◽  
High Yield ◽  
Formyl Group ◽  
Bond Yields ◽  
Terminal Double Bond ◽  
Subsequent Addition

AbstractA base-mediated intramolecular hydroalkoxylation that was used to prepare a series of seven-membered S,O-heterocycles is described. 2-Thiopropargyl-3-hydroxymethyl quinolines were prepared starting from 2-mercaptoquinoline-3-carbaldehydes, via S-propargylation and reduction of a formyl group. Interestingly, 2-mercaptopropargyl-3-hydroxymethyl quinolines were converted into the corresponding oxathiepinoquinolines in the presence of t-BuOK. It is proposed that the S-propargyl moiety, in the presence of base, is converted into its allenyl isomer; subsequent addition of a hydroxyl group to the terminal double bond yields the 3-methyl-5H-[1,4]oxathiepino[5,6-b]quinoline in good to high yield. Notably, the procedure is adaptable to the conversion of N-propargyl indole-2-methanol into the corresponding intramolecular hydroalkoxylation product.

scholarly journals Application of Enzymes in Regioselective and Stereoselective Organic Reactions

Catalysts ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 832
Author(s):  
Ruipu Mu ◽  
Zhaoshuai Wang ◽  
Max C. Wamsley ◽  
Colbee N. Duke ◽  
Payton H. Lii ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
High Efficiency ◽  
Enzyme Commission ◽  
High Yield ◽  
Enzymatic Reactions ◽  
Design Strategies ◽  
Enzyme Design ◽  
Comprehensive Overview ◽  
Effective Performance ◽  
Insight Into

Nowadays, biocatalysts have received much more attention in chemistry regarding their potential to enable high efficiency, high yield, and eco-friendly processes for a myriad of applications. Nature’s vast repository of catalysts has inspired synthetic chemists. Furthermore, the revolutionary technologies in bioengineering have provided the fast discovery and evolution of enzymes that empower chemical synthesis. This article attempts to deliver a comprehensive overview of the last two decades of investigation into enzymatic reactions and highlights the effective performance progress of bio-enzymes exploited in organic synthesis. Based on the types of enzymatic reactions and enzyme commission (E.C.) numbers, the enzymes discussed in the article are classified into oxidoreductases, transferases, hydrolases, and lyases. These applications should provide us with some insight into enzyme design strategies and molecular mechanisms.

scholarly journals Squalene-Hopene Cyclases

2011 ◽  
Vol 77 (12) ◽  
pp. 3905-3915 ◽  
Author(s):  
Gabriele Siedenburg ◽  
Dieter Jendrossek
Keyword(s):  
Common Ancestor ◽  
Amino Acid Sequences ◽  
Enzymatic Reactions ◽  
Covalent Bonds ◽  
Content Type ◽  
Oxidosqualene Cyclase ◽  
Ring Structures ◽  
One Step ◽  
Alicyclobacillus Acidocaldarius ◽  
Eukaryotic Organisms

ABSTRACTHopanoids and sterols are members of a large group of cyclic triterpenoic compounds that have important functions in many prokaryotic and eukaryotic organisms. They are biochemically synthesized from linear precursors (squalene, 2,3-oxidosqualene) in only one enzymatic step that is catalyzed by squalene-hopene cyclase (SHC) or oxidosqualene cyclase (OSC). SHCs and OSCs are related in amino acid sequences and probably are derived from a common ancestor. The SHC reaction requires the formation of five ring structures, 13 covalent bonds, and nine stereo centers and therefore is one of the most complex one-step enzymatic reactions. We summarize the knowledge of the properties of triterpene cyclases and details of the reaction mechanism ofAlicyclobacillus acidocaldariusSHC. Properties of other SHCs are included.

scholarly journals Cathodic hydrodimerization of nitroolefins

2015 ◽  
Vol 11 ◽  
pp. 1163-1174 ◽  
Author(s):  
Michael Weßling ◽  
Hans J Schäfer
Keyword(s):  
Double Bond ◽  
Nitro Group ◽  
Bond Formation ◽  
Cathodic Reduction ◽  
High Yield ◽  
Easy Access ◽  
Electrolysis Cell ◽  
Aldehydes And Ketones ◽  
Nef Reaction

Nitroalkenes are easily accessible in high variety by condensation of aldehydes with aliphatic nitroalkanes. They belong to the group of activated alkenes that can be hydrodimerized by cathodic reduction. There are many olefins with different electron withdrawing groups used for cathodic hydrodimerization, but not much is known about the behaviour of the nitro group. Synthetic applications of this group could profit from the easy access to nitroolefins in large variety, the C–C bond formation with the introduction of two nitro groups in a 1,4-distance and the conversions of the nitro group by reduction to oximes and amines, the conversion into aldehydes and ketones via the Nef reaction and base catalyzed condensations at the acidic CH bond. Eight 1-aryl-2-nitro-1-propenes have been electrolyzed in an undivided electrolysis cell to afford 2,5-dinitro-3,4-diaryl hexanes in high yield. The 4-methoxy-, 4-trifluoromethyl-, 2-chloro- and 2,6-difluorophenyl group and furthermore the 2-furyl and 2-pyrrolyl group have been applied. The reaction is chemoselective as only the double bond but not the nitro group undergoes reaction, is regioselective as a ß,ß-coupling with regard to the nitro group and forms preferentially two out of six possible diastereomers as major products.

scholarly journals TAMI-55. THE EVOLUTIONARY ENIGMA OF FATTY ACID DESATURATION IN GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii225-ii225
Author(s):  
Nicole Oatman ◽  
Julie Reisz ◽  
Angelo D’Alessandro ◽  
Biplab Dasgupta
Keyword(s):  
Fatty Acid ◽  
Double Bond ◽  
Acyl Chain ◽  
Enzymatic Reaction ◽  
Monounsaturated Fatty Acids ◽  
Fatty Acid Desaturation ◽  
Dual Function ◽  
Storage Lipids ◽  
Essential Components ◽  
Unexpected Findings

Abstract Fatty acid desaturation is an enzymatic reaction in which a double bond is introduced into an acyl chain. Of the four functionally distinct desaturase subfamilies, the First Desaturase Family of enzymes introduce the first double bond into a saturated fatty acid, resulting in the synthesis of monounsaturated fatty acids (MUFA). MUFA are essential components of membrane and storage lipids and exert a profound influence on the fluidity of biological membranes. A disequilibrium in saturated to unsaturated fatty acid ratio alters cell growth, differentiation and response to external stimuli, and thus affects a range of pathologies including cancer. The most abundant and key First Desaturase Family enzyme is the delta 9 desaturate called Stearoyl Co-A Desaturase (SCD and SCD5 in humans, and SCD1-4 in mice). SCD desaturates Stearoyl-CoA (C18) and palmitoyl-CoA (C16) to oleoyl-CoA (C18:1) and palmitoyl-CoA (C16:1), respectively. Besides SCD, the only known First Desaturase in mammals with dual function is FADS2 which desaturates palmitate to Sapienate (C16:1, a positional isomer of palmitoleate) in skin cells. A recent study showed that some cancer cells can use FADS2 to bypass the SCD reaction. SCD and SCD5 are by far the most abundant desaturases expressed in the human brain. We made an unexpected discovery that SCD undergoes monoallelic codeletion with PTEN on chromosome 10, and is also highly methylated in glioblastoma (GBM). More surprisingly, all GBM cell lines with SCD codeletion/methylation (that expressed very little SCD protein) are completely resistant to SCD/SCD5 inhibition, yet their phospholipids contained abundant oleic acid. It is unknown if GBMs bypassed SCD, but retained the delta 9 desaturation reaction through a novel enzymatic activity. Our targeted and untargeted metabolomics studies revealed unexpected findings that cannot be explained by conventional wisdom, and may lead to identification of novel lipogenic targets in GBM.

Ultrasound promotes enzymatic reactions by acting on different targets: Enzymes, substrates and enzymatic reaction systems

2018 ◽  
Vol 119 ◽  
pp. 453-461 ◽  
Author(s):  
Danli Wang ◽  
Lufeng Yan ◽  
Xiaobin Ma ◽  
Wenjun Wang ◽  
Mingming Zou ◽  
...  
Keyword(s):  
Enzymatic Reaction ◽  
Enzymatic Reactions ◽  
Reaction Systems

scholarly journals Establishing MALDI-TOF as Versatile Drug Discovery Readout to Dissect the PTP1B Enzymatic Reaction

2018 ◽  
Vol 23 (6) ◽  
pp. 561-573 ◽  
Author(s):  
Martin Winter ◽  
Tom Bretschneider ◽  
Carola Kleiner ◽  
Robert Ries ◽  
Jörg P. Hehn ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Throughput Screening ◽  
Tyrosine Phosphatase ◽  
Enzymatic Reaction ◽  
Enzymatic Reactions ◽  
Label Free ◽  
Ionization Time ◽  
Maldi Tof ◽  
Ptp1b Inhibitors ◽  
Promising Perspective

Label-free, mass spectrometric (MS) detection is an emerging technology in the field of drug discovery. Unbiased deciphering of enzymatic reactions is a proficient advantage over conventional label-based readouts suffering from compound interference and intricate generation of tailored signal mediators. Significant evolvements of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS, as well as associated liquid handling instrumentation, triggered extensive efforts in the drug discovery community to integrate the comprehensive MS readout into the high-throughput screening (HTS) portfolio. Providing speed, sensitivity, and accuracy comparable to those of conventional, label-based readouts, combined with merits of MS-based technologies, such as label-free parallelized measurement of multiple physiological components, emphasizes the advantages of MALDI-TOF for HTS approaches. Here we describe the assay development for the identification of protein tyrosine phosphatase 1B (PTP1B) inhibitors. In the context of this precious drug target, MALDI-TOF was integrated into the HTS environment and cross-compared with the well-established AlphaScreen technology. We demonstrate robust and accurate IC50 determination with high accordance to data generated by AlphaScreen. Additionally, a tailored MALDI-TOF assay was developed to monitor compound-dependent, irreversible modification of the active cysteine of PTP1B. Overall, the presented data proves the promising perspective for the integration of MALDI-TOF into drug discovery campaigns.

Sign in / Sign up

Export Citation Format

Share Document