Kaygan Kaya Üniversitesi tarafından sağlanan Fonlama. Biz onların anlayışlar için T. Boron III (Kaygan Kaya Üniversitesi) ve C. Haney (Pennsylvania Üniversitesi) teşekkür etmek istiyorum.

Ni-Schiff-baz Complex 1. Hidroliz <ol><li> Oda sıcaklığında 250 mL&#39;lik tabanı yuvarlak bir şişeye karıştırılarak N, N-dimetilformamid (DMF), 40 mL Ni-PBP-Schiff-baz kompleksi 1 mmol eritin. </li><li> 0.2 M sulu EDTA çözeltisi, pH 4.5, 60 mL ekleyin. </li><li> Manyetik bir karıştırma çubuğu kullanılarak ve plaka karıştırın, bir gece boyunca bir araya çözelti karıştırılır. Schiff-baz kompleksi hidrolize gibi, renk beyaz bir koyu kırmızı yönelecektir. </li><li> herhangi bir kırmızı boyama yokluğu ile gösterildiği gibi reaksiyonun tamamlanmasından sonra, bir 250 ml ayırıcı bir huniye reaksiyon aktarın. </li><li> 50 ml diklorometan ilave ayırıcı huni kapağı ve karıştırın. Bir atık behere organik yıkama boşaltın. PBP ve kalan Ni PBP-Schiff-baz kompleksi kaldırmak için bu işlem üç kez tekrarlayın. 250 mL&#39;lik yuvarlak dipli bir şişede kalan sulu tabakayı toplayın. </li></ol> Hidrolize olan Amino Asit 2. Fmoc koruma <ol><li&gt; Katı sodyum bikarbonat kullanılarak pH 7&#39;ye yukarıda tarif edilen adım 1.5 izole sulu tabaka ayarlayın. pH periyodik olarak pH test şeritleri kullanarak kontrol edin. </li><li> çözeltiye 168 mg sodyum bikarbonat (2.00 mmol, 2 eşdeğer) ilave edin ve bir manyetik karıştırma çubuğu kullanılarak karıştırıldı ve plaka karıştırın. </li><li> 10 mL&#39;lik bir şişe içinde dioksan çok az miktarda (yaklaşık 4 ya da 5 mL) içinde 337 mg Fmoc N-hidroksisüksinimit ester (1.00 mmol, 1 eşdeğer) içinde çözülür. Sulu çözeltiye Bu çözeltisini ve gece boyunca karıştırın. </li><li> Reaksiyon, gece boyunca karışmaya bırakıldıktan sonra, 1 M hidroklorik asit ile pH 2&#39;ye elde edilen çözeltiyi asitleştirmek. pH periyodik olarak pH test şeritleri kullanarak kontrol edin. </li><li> 250 mL&#39;lik bir ayırma hunisine aktarın ve reaksiyon 50 mL etil asetat ilave edin. , Ayrıcı bir huni kapağı iyice karıştırın ve 250 ml bir erlenmeyer şişesi içinde, organik faz toplanır. Organik özler birleştirerek, bu işlem iki kez daha tekrarlayın. Magnezyum Sülfat, kabaca 3 g Birleştirilen organik özler kurutulure. </li><li> Ham Fmoc-korumalı amino asit elde etmek için bir dönen buharlaştıncı kullanarak Birleştirilen organik özler konsantre edilir. </li></ol>

<ol>
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Ed. 40 (10), 1948-1951 (2001).</li><li>Zhou, S., Wang, J., Lin, D., Zhao, F., Liu, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Enantioselective+synthesis+of+2-substituted-tetrahydroisoquinolin-1-yl+glycine+derivatives+via+oxidative+cross-dehydrogenative+coupling+of+tertiary+amines+and+chiral+nickel(II)+glycinate.">Enantioselective synthesis of 2-substituted-tetrahydroisoquinolin-1-yl glycine derivatives via oxidative cross-dehydrogenative coupling of tertiary amines and chiral nickel(II) glycinate.</a> J. Org. Chem. 78 (22), 11204-11212 (2013).</li><li>Belokon, Y. 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A., Kelly, D. E., Wolfe, A. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Large-scale+syntheses+of+Fmoc-protected+non-proteogenic+amino+acids:+useful+building+blocks+for+combinatorial+libraries.">Large-scale syntheses of Fmoc-protected non-proteogenic amino acids: useful building blocks for combinatorial libraries.</a> Org. Process Res. Dev. 5 (4), 445-449 (2001).</li><li>Cruz, L. J., Beteta, N. G., Ewenson, A., Albericio, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=&amp;#34;One-pot&amp;#34;,+preparation+of+N-carbamate+protected+amino+acids+via+the+azide.">&amp;#34;One-pot&amp;#34;, preparation of N-carbamate protected amino acids via the azide.</a> Org Process Res. Dev. 8 (6), 920-924 (2004).</li><li>Hart, J. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Ullmann's Encyclopedia of Industrial Chemistry. , (2000).</li><li>Adamson, J. G., Blaskovich, M. A., Groenevelt, H., Lajoie, G. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Simple+and+convenient+synthesis+of+tert-butyl+ethers+of+Fmoc-serine,+Fmoc-threonine,+and+Fmoc-tyrosine.">Simple and convenient synthesis of tert-butyl ethers of Fmoc-serine, Fmoc-threonine, and Fmoc-tyrosine.</a> J. Org. Chem. 56 (10), 3447-3449 (1991).</li><li>Seyfried, M. S., Lauber, B. S., Luedtke, N. 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Yazarlar ifşa hiçbir şey yok.

Yukarıda tarif edilen protokol iki kritik adımları hafif pH koşulları ve bu izole edilmiş amino asidin daha sonra Fmoc koruma altında bir Ni-Schiff baz kompleksine bir amino asit omurgasına izole edilmesini kolaylaştırmak için yeteneği yararlıdır. İlk adım kompleksinden amino asidin salınmasını kolaylaştırmak için EDTA ihtiva eden bir DMF / su çözeltisi karıştırılarak içermektedir. Kalıntı, karmaşık ya da organik yan ürünler kolaylıkla ekstre ile temizlenebilir. Bu protokol, ikinci a?...

Doğada bulunan yirmi doğal olarak meydana gelen amino asitler aşağıdaki farklı doğal olmayan amino asitler (UAA) &#39;ın yatak yan zincirleri geniş bir uygulama aralığı içinde faydalı oldukları bulunmuştur. Bu, UAA &#39;s sentezi, ancak, yan zincirlerin yapı ve amino asit omurgasına stereokimyasına bağlı olarak zor olabilir. Bir nikel Schiff baz kompleksine bağlamında glisin CH bond aktivasyon a, β-diamino asitler 1 ve 2 ya da heterosiklik yan zincirler fluorinatlı UAA en yatak içeren amino asit türevlerinin çeşitli üretmek için kullanılmıştır. 3 Doğal olmayan yan zincirler eklenmesinden sonra, UAA en tipik haliyle hidroklorik asit 4 geri akış ile Schiff baz kompleksine çıkarılır ve daha sonra iyon değişimi kromatografisi kullanılarak izole edilir işlevselleştirilmiş. genellikle verimli olsa da, bu protokol bir üretirKatı faz peptit sentezi ile (SPPS) içinde kullanım için uygun olabilir amino asitlik. SPPS doğası bozulmamış bu koruyucu gruplarla UAA en izolasyonunu önler asit-labil yan zincir koruma gruplarının varlığını ve tipik Ni-Schiff bazı ayrışma koşulları güçlü asidik doğası gerektirir. Bildiğimiz kadarıyla, tek alternatif ayrıştırma yöntemi bildirilmiştir: etilendiamintetraasetik asit (EDTA) ve hidrazin kullanılması, yüksek sıcaklıklarda, kendilerini bazı yan zincir gibi ftalimitler gibi koruma grupları için uygun olmayabilir 5 koşullar, bu. <img alt="Şekil 1" src="/files/ftp_upload/55677/55677fig1.jpg" /> Şekil 1: Ni2 +, PBP ve Glisin (Giy) Ni PBP-Gly sentezi. <a href="http://ecsource.jove.com/files/ftp_upload/55677/55677fig1large.jpg" target="_blank">Bu rakamın büyük halini görmek için buraya tıklayın.</a> </a&gt; Burada, Ni-PBP-Gly (Şekil 1), bir Ni-Schiff baz kompleksine hidrolizi için bir yöntem sunulmaktadır. Ni2 +, glisin ve piridin-2-karboksilik asit (2-benzoil-fenil) -amid (PBP), 6 türetilmiş Bu kompleks, UAA en çeşitli sentezi için yararlı bir platform olduğu gösterilmiştir ve kolay bir edilmiştir erişilebilen iki aşamalı bir sentetik yol kullanılarak. Bu kompleksin 7 sentezi literatürde-konmuşturlar yüksek verimde olan. 6 Sonuçlarımız, aşağıda tarif edilen UAA en taşıyan asit kararsız yan zincir koruma grupları ile kullanım için uygun olan nötr pH koşulları hafif asidik EDTA kullanılarak hidroliz şartları uygulanabilirliğini göstermektedir. Hidrolizi takiben, elde edilen sulu çözelti, izole edilebilir ve Fmoc-korumalı amino asit elde standart Fmoc koruma koşullarında (Şekil 2) hemen tabi tutuldu. Şekil 2: Hidroliz ve Ni-PBP-Gly İzole bir şekilde bir Amino Asit Fmoc-koruma. Reaksiyon koşulları: i. EDTA (12 eşdeğer), pH 4.5; ii. pH 7&#39;ye etil asetat yıkama ve ayarlanması; iii. Fmoc-OSu (1 eşdeğer), NaHCO 3 (2 eşdeğ) eklenir. <a href="http://ecsource.jove.com/files/ftp_upload/55677/55677fig2large.jpg" target="_blank">Bu rakamın büyük halini görmek için buraya tıklayın.</a>

<table><tbody><tr><td>Ni-PBP-Gly</td><td></td><td></td><td>Synthesized from published protocol</td></tr><tr><td>DMF</td><td>Fisher</td><td>D119-4</td><td></td></tr><tr><td>EDTA</td><td>Fisher</td><td>S311-100</td><td></td></tr><tr><td>Dichloromethane</td><td>Acros</td><td>AC610050040</td><td></td></tr><tr><td>Sodium Bicarbonate</td><td>Fisher</td><td>S233-500</td><td></td></tr><tr><td>Fmoc-OSu</td><td>Chem-Impex</td><td>&quot;00147&quot;</td><td></td></tr><tr><td>Dioxane</td><td>Fisher</td><td>D111-500</td><td></td></tr><tr><td>Hydrochloric Acid</td><td>Fisher</td><td>A144-500</td><td></td></tr><tr><td>Ethyl Acetate</td><td>Acros</td><td>AC610060040</td><td></td></tr><tr><td>Magnesium Sulfate</td><td>Fisher</td><td>M65-500</td><td></td></tr><tr><td>ZEOPrep 60ECO Silica Gel</td><td>ZEOChem</td><td></td><td></td></tr><tr><td>Hexanes</td><td>Fisher</td><td>3200250.650.443</td><td></td></tr><tr><td>Chromatography Column</td><td></td><td></td><td></td></tr><tr><td>pH Test Strips</td><td></td><td></td><td></td></tr><tr><td>Rotary Evaporator</td><td></td><td></td><td></td></tr><tr><td>250 mL Separatory Funnel</td><td></td><td></td><td></td></tr><tr><td>250 mL Round Bottom Flask</td><td></td><td></td><td></td></tr><tr><td>Stir Bar</td><td></td><td></td><td></td></tr><tr><td>Stir Plate</td><td></td><td></td><td></td></tr></tbody></table>

hydrolysis of a ni-schiff-base complex using conditions suitable for retention of acid-labile protecting groups

Doğal olmayan amino asitler, doğada yaygın şekilde görülmeyen yan zincir işlevsellikleri ihtiva eden bir amino asit, giderek sentetik peptid dizileri bulunur. Bazı doğal olmayan amino asitlerin sentezi genellikle nikel katyon ile stabilize edilmiş bir Schiff-baz içeren bir ön-madde kullanımını içerir. Doğal olmayan yan zincirler, bu Schiff-baz kompleksi içinde bulunan bir amino asit omurgası üzerinde monte edilebilir. Elde edilen doğal olmayan amino asit, daha sonra, tipik olarak kuvvetli asitli çözelti içinde geri akış kullanılarak, Schiff-baz bu kompleks ile hidrolizi ile izole edilebilir. doğal olmayan amino asitler mikrodalga destekli bir katı-faz peptid sentezi kullanılmak için bu yüksek derecede asidik koşullar asit kararsız yan zincir koruma grupları, gerekli kaldırabilir. Bu çalışmada, etkin bir hidroliz ve bir Ni-Schiff baz kompleksine izole edilen bir amino asidin daha sonra Fmoc koruma sunmaktadır. Bu çalışmada sunulan Hidroliz koşulları asit-labil s tutma için uygun olanide-zincir koruma gruplarını ve doğal olmayan amino asit çeşitli substratlar için adapte edilebilir.

Bu sert pH koşullarında gerek kalmadan Schiff-baz etkin bir sulu hidroliz izin verebilir Ni PBP-Gly kompleksinden Ni + 2 &#39;nin bu kaldırılmasını hipotezini kurduk. EDTA, ucuz ve iyi incelenmiş şelatlayıcı madde olduğu için, 10 biz Ni PBP-Gly bir çözeltiye EDTA ilavesi ve böylece kompleksin hidrolizi teşvik Ni + 2 iyonlarının çelasyonunu kolaylaştırmak varsaydık. <p class="jove_content" fo:keep-together.within-page...

Watch this Scientific Journal Video about Hydrolysis of a Ni-Schiff-Base Complex Using Conditions Suitable for Retention of Acid-labile Protecting Groups at JoVE.com

Hydrolysis of a Ni-Schiff-Base Complex Using Conditions Suitable for Retention of Acid-labile Protecting Groups

Burada, etkili bir hidroliz ve bir Ni-Schiff-baz kompleksi izole edilen bir amino asidin daha sonra Fmoc koruma sunmaktadır. asit-labil yan zincir koruma gruplarının tutma gerekli olduğunda burada sunulan Hidroliz koşulları kullanılmak üzere uygundur. Bu teknik, doğal olmayan amino asit çeşitli substratlar için adapte edilebilir.

Koruma Grupları aside dayanıksız Saklanmasına için uygun bir Ni-Schiff-Base hidrolizi Kompleksi kullanma Koşullar

Unnatural amino acids, amino acids containing side-chain functionalities not commonly seen in nature, are increasingly found in synthetic peptide ...

hydrolysis-ni-schiff-base-complex-using-conditions-suitable-for

Research

JoVE Journal

Biochemistry

9.6K Görüntüleme.  Slippery Rock University.  Burada, etkili bir hidroliz ve bir Ni-Schiff-baz kompleksi izole edilen bir amino asidin daha sonra Fmoc koruma sunmaktadır. asit-labil yan zincir koruma gruplarının tutma gerekli olduğunda burada sunulan Hidroliz koşulları kullanılmak üzere uygundur. Bu teknik, doğal olmayan amino asit çeşitli substratlar için adapte edilebilir. 

Video: Hydrolysis of a Ni-Schiff-Base Complex Using Conditions Suitable for Retention of Acid-labile Protecting Groups

A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles

Nanomedicine is an emerging form of therapy that harnesses the unique properties of particles that are nanometers in scale for biomedical application. Improving drug delivery to maximize therapeutic outcomes and to reduce drug-associated side effects are some of the cornerstones of present-day nanomedicine. Nanoparticles in particular have found a wide application in cancer treatment. Nanoparticles that offer a high degree of flexibility in design, application, and production based on the tumor microenvironment are projected to be more effective with rapid translation into clinical practice. The polymeric micellar nano-carrier is a popular choice for drug delivery applications.
In this article, we describe a simple and effective protocol for synthesizing drug-loaded, disulfide cross-linked micelles based on the self-assembly of a well-defined amphiphilic linear-dendritic copolymer (telodendrimer, TD). TD is composed of polyethylene glycol (PEG) as the hydrophilic segment and a thiolated cholic acid cluster as the core-forming hydrophobic moiety attached stepwise to an amine-terminated PEG using solution-based peptide chemistry. Chemotherapy drugs, such as paclitaxel (PTX), can be loaded using a standard solvent evaporation method. The O2-mediated oxidation was previously utilized to form intra-micellar disulfide cross-links from free thiol groups on the TDs. However, the reaction was slow and not feasible for large-scale production. Recently, an H2O2-mediated oxidation method was explored as a more feasible and efficient approach, and it was 96 times faster than the previously reported method. Using this approach, 50 g of PTX-loaded, disulfide cross-linked nanoparticles have been successfully produced with narrow particle size distribution and high drug loading efficiency. The stability of the resulting micelle solution is analyzed using disrupting conditions such as co-incubation with a detergent, sodium dodecyl sulfate, with or without a reducing agent. The drug-loaded, disulfide cross-linked micelles demonstrated less hemolytic activity when compared to their non-cross-linked counterparts.

To deliver cancer drugs to tumor sites with high specificity and reduced side effects, new methods based on nanoparticles are required. Here, we describe disulfide cross-linked micelles that can be easily prepared by hydrogen peroxide-mediated oxidation and are able to dissociate efficiently under a reducing tumor environment to release payloads.

Döner disülfür Çapraz bağlı misellerin Üretimi için basit ve etkin Yaklaşım

Nanomedicine is an emerging form of therapy that harnesses the unique properties of particles that are nanometers in scale for biomedical application. ...

Biyokimya

Separation of Aldehydes and Reactive Ketones from Mixtures Using a Bisulfite Extraction Protocol

The purification of organic compounds is an essential component of routine synthetic operations. The ability to remove contaminants into an aqueous layer by generating a charged structure provides an opportunity to use extraction as a simple purification technique. By combining the use of a miscible organic solvent with saturated sodium bisulfite, aldehydes and reactive ketones can be successfully transformed into charged bisulfite adducts that can then be separated from other organic components of a mixture by the introduction of an immiscible organic layer. Here, we describe a simple protocol for the removal of aldehydes, including sterically-hindered neopentyl aldehydes and some ketones, from chemical mixtures. Ketones can be separated if they are sterically unhindered cyclic or methyl ketones. For aliphatic aldehydes and ketones, dimethylformamide is used as the miscible solvent to improve removal rates. The bisulfite addition reaction can be reversed by basification of the aqueous layer, allowing for the re-isolation of the reactive carbonyl component of a mixture.

Here, we present a protocol to remove aldehydes and reactive ketones from mixtures by a liquid-liquid extraction protocol directly with saturated sodium bisulfite in a miscible solvent. This combined protocol is rapid and facile to perform. The aldehyde or ketone can be re-isolated by the basification of the aqueous layer.

Aldehitler ve ketonlar reaktif ayrılması Bisülfit ayıklama protokolü kullanılarak karışımları

The purification of organic compounds is an essential component of routine synthetic operations. The ability to remove contaminants into an aqueous layer ...

Kimya

Imine Metathesis by Silica-Supported Catalysts Using the Methodology of Surface Organometallic Chemistry

With this protocol, a well-defined singlesite silica-supported heterogeneous catalyst [(&#8801;Si-O-)Hf(=NMe)(&#951;1-NMe2)] is designed and prepared according to the methodology developed by surface organometallic chemistry (SOMC). In this framework, catalytic cycles can be determined by isolating crucial intermediates. All air-sensitive materials are handled under inert atmosphere (using gloveboxes or a Schlenk line) or high vacuum lines (HVLs, &#60;10-5 mbar). The preparation of SiO2-700 (silica dehydroxylated at 700 &#176;C) and subsequent applications (the grafting of complexes and catalytic runs) requires the use of HVLs and double-Schlenk techniques. Several well-known characterization methods are used, such as Fourier-transform infrared spectroscopy (FTIR), elemental microanalysis, solid-state nuclear magnetic resonance spectroscopy (SSNMR), and state-of-the-art dynamic nuclear polarization surface enhanced NMR spectroscopy (DNP-SENS). FTIR and elemental microanalysis permit scientists to establish the grafting and its stoichiometry. 1H and 13C SSNMR allows the structural determination of the hydrocarbon ligands coordination sphere. DNP SENS is an emerging powerful technique in solid characterization for the detection of poorly sensitive nuclei (15N, in our case). SiO2-700 is treated with about one equivalent of the metal precursor compared to the amount of surface silanol (0.30 mmol&#183;g-1) in pentane at room temperature. Then, volatiles are removed, and the powder samples are dried under dynamic high vacuum to afford the desired materials [(&#8801;Si-O-)Hf(&#951;2&#960;-MeNCH2)(&#951;1-NMe2)(&#951;1-HNMe2)]. After a thermal treatment under high vacuum, the grafted complex is converted into metal imido silica complex [(&#8801;Si-O-)Hf(=NMe)(&#951;1-NMe2)]. [(&#8801;Si-O-)Hf(=NMe)(&#951;1-NMe2)] effectively promotes the metathesis of imines, using the combination of two imine substrates, N-(4-phenylbenzylidene)benzylamine, or N-(4-fluorobenzylidene)-4-fluoroaniline, with N-benzylidenetert-butylamine as substrates. A significantly lower conversion is observed with the blank runs; thus, the presence of the imido group in [(&#8801;Si-O-)Hf(=NMe)(&#951;1-NMe2)] is correlated to the catalytic performance.

A new group IV metal catalyst for imine metathesis is prepared by grafting amine metal complex onto dehydroxylated silica. Surface metal fragments are characterized using FT-IR, elemental microanalysis, and solid-state NMR spectroscopy. Further dynamic nuclear polarization surface enhanced NMR spectroscopy experiments complement the determination of the coordination sphere.

Yüzey Organometalik Kimya metodolojisini kullanan Silika Destekli Katalizörler tarafından Imine Metatez

With this protocol, a well-defined singlesite silica-supported heterogeneous catalyst [(&#8801;Si-O-)Hf(=NMe)(&#951;1-NMe2)] is designed and prepared ...

Preparation of SNS Cobalt(II) Pincer Model Complexes of Liver Alcohol Dehydrogenase

Chemical model complexes are prepared to represent the active site of an enzyme. In this protocol, a family of tridentate pincer ligand precursors (each possessing two sulfur and one nitrogen donor atom functionalities (SNS) and based on bis-imidazole or bis-triazole compounds) are metallated with CoCl2&#183;6H2O to afford tridentate SNS pincer cobalt(II) complexes. Preparation of the cobalt(II) model complexes for liver alcohol dehydrogenase is facile. Based on a quick color change upon adding the CoCl2&#183;6H2O to acetonitrile solution that contains the ligand precursor, the complex forms rapidly. Formation of the metal complex is complete after allowing the solution to reflux overnight. These cobalt(II) complexes serve as models for the zinc active site in liver alcohol dehydrogenase (LADH). The complexes are characterized using single crystal X-ray diffraction, electrospray mass spectrometry, ultra-violet visible spectroscopy, and elemental analysis. To accurately determine the structure of the complex, its single crystal structure must be determined. Single crystals of the complexes that are suitable for X-ray diffraction are then grown via slow vapor diffusion of diethyl ether into an acetonitrile solution that contains the cobalt(II) complex. For high quality crystals, recrystallization typically takes place over a 1 week period, or longer. The method can be applied to the preparation of other model coordination complexes and can be used in undergraduate teaching laboratories. Finally, it is believed that others may find this recrystallization method to obtain single crystals beneficial to their research.

Preparation of SNS CobaltII Pincer Model Complexes of Liver Alcohol Dehydrogenase

The preparation of SNS pincer cobalt(II) model complexes of liver alcohol dehydrogenase is presented here. The complexes can be prepared by reacting the ligand precursor with CoCl2&#183;6H2O and can then be recrystallized by allowing diethyl ether to slowly diffuse into an acetonitrile solution that contains the cobalt complex.

Karaciğer Alkol Dehidrogenaz SNS Kobalt(II) Kıskaç Model Kompleksleri Hazırlanması

Chemical model complexes are prepared to represent the active site of an enzyme. In this protocol, a family of tridentate pincer ligand precursors (each ...

Protection of Alcohols

This lesson delves into the concept of protection and deprotection of a functional group fundamental to synthetic organic chemistry. These phenomena are explained in the context of aliphatic and aromatic alcohols.
<h4>Protection</h4>
It defines a protecting group as the masking agent to make the more reactive species inert to a given set of conditions. This concept is depicted via the illustration of liquid flow through different outlets in an assembly of pipes. The analogy helps to understand the role of a protecting group in reaction selectivity, as in the case of the organolithium alkylation of a halide in the presence of a competing acidic alcohol group. The example shows how protection of the alcohol group helps to achieve the alkylation of the halide. Popular protecting groups for alcohols include the trialkylsilyl family for nucleophiles or carbon and nitrogen bases and the tetrahydropyranyl (THP) group for strong bases. In the former example, the halide of the trialkylsilyl derivative reacts with the alcohol in the presence of a nucleophilic catalyst to generate a trialkylsilyl ether.
<h4>Deprotection</h4>
Every protection is followed by deprotection after the intended reaction. The deprotection restores the system to its native state. In protection with trialkylsilyl groups, deprotection is achieved using fluoride salts like tetra-n-butylammonium fluoride (TBAF) that are soluble in organic solvents. Here, the re-protonation of the oxygen regenerates the native alcohol. In the case of protection with THP, deprotection is achieved using acid hydrolysis.
<h4>Principle of design</h4>
The lesson also elucidates the principles behind the design of a protecting group using an illustration of a house under varying external weather conditions. It demonstrates the selectivity offered by a protecting group in a specific environment. For instance, THP protects alcohol from strong bases. The acetal formed in this case is stable towards bases but susceptible to acid hydrolysis.
Apart from the reaction conditions, the reactivity of the molecule to be protected also plays a key role in designing a suitable protecting group. For example, methyl ethers&#8217; ability to protect phenols is found inappropriate for aliphatic alcohols. Here, the stability of the corresponding leaving groups during deprotection plays a key role. For example, the alkoxides, unlike phenoxides, are poor leaving groups for deprotection with hydrogen bromide.
The following table summarizes the various protection/deprotection groups for different types of alcohols and related conditions:
<table style="margin-left: auto; margin-right: auto;">
	<tbody style="border: 1px solid black;">
		<tr>
			<td style="color: black; border: 1px solid black; text-align: center;">Protecting group</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Structure</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Protects</td>
			<td style="color: black; border: 1px solid black; text-align: center;">From</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Protection</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Deprotection</td>
		</tr>
		<tr>
			<td style="color: black; border: 1px solid black; text-align: center;">Trialkylsilyl (R3Si&#8211;), 
			e.g., TBDMS</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Me3Si&#8211;OR 
			(Me3C)Me2Si&#8211;OR</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Alcohols 
			(OH in general)</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Nucleophiles, 
			C or N bases</td>
			<td style="color: black; border: 1px solid black; text-align: center;">R3SiCl, 
			base</td>
			<td style="color: black; border: 1px solid black; text-align: center;">H+, H2O, 
			or F&#8722;</td>
		</tr>
		<tr>
			<td style="color: black; border: 1px solid black; text-align: center;">Tetrahydropyranyl 
			(THP)</td>
			<td style="color: black; border: 1px solid black; text-align: center;"><img alt="Figure1" src="/files/ftp_upload/11927/Figure_1-11927.svg" style="text-align: center; height: 50px;" /></td>
			<td style="color: black; border: 1px solid black; text-align: center;">Alcohols 
			(OH in general)</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Strong bases</td>
			<td style="color: black; border: 1px solid black; text-align: center;">3,4-Dihydropyran, 
			H+</td>
			<td style="color: black; border: 1px solid black; text-align: center;">H+, H2O</td>
		</tr>
		<tr>
			<td style="color: black; border: 1px solid black; text-align: center;">Benzyl ether 
			(OBn)</td>
			<td style="color: black; border: 1px solid black; text-align: center;"><img alt="Figure2" src="/files/ftp_upload/11927/Figure_2-11927.svg" style="text-align: center; height: 50px;" /></td>
			<td style="color: black; border: 1px solid black; text-align: center;">Alcohols 
			(OH in general)</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Almost everything</td>
			<td style="color: black; border: 1px solid black; text-align: center;">NaH, BnBr</td>
			<td style="color: black; border: 1px solid black; text-align: center;">H2, Pd/C, 
			or HBr</td>
		</tr>
		<tr>
			<td style="color: black; border: 1px solid black; text-align: center;">Methyl ether 
			(ArOMe)</td>
			<td style="color: black; border: 1px solid black; text-align: center;"><img alt="Figure3" src="/files/ftp_upload/11927/Figure_3-11927.svg" style="text-align: center; height: 50px;" /></td>
			<td style="color: black; border: 1px solid black; text-align: center;">Phenols 
			(ArOH)</td>
			<td style="color: black; border: 1px solid black; text-align: center;">Bases</td>
			<td style="color: black; border: 1px solid black; text-align: center;">NaH, MeI, or 
			(MeO)2SO2</td>
			<td style="color: black; border: 1px solid black; text-align: center;">BBr3, HBr, HI, 
			Me3SiI</td>
		</tr>
	</tbody>
</table>

Protection and Deprotection of Alcohols and Phenols

Alkollerin Korunması

This lesson delves into the concept of protection and deprotection of a functional group fundamental to synthetic organic chemistry. These phenomena are ...

Education

JoVE Core

Organik Kimya

Unit 1

Alkoller ve Fenoller

KEY TERMS AND CONCEPTS

Preparation of Carboxylic Acids: Hydrolysis of Nitriles

Nitriles (R&#8211;CN) can be converted into carboxylic acids (R&#8211;COOH) upon treatment with aqueous acids, i.e., upon hydrolysis of nitriles. Under base-catalyzed conditions, carboxylate anions (R&#8211;COO&#8722;) are formed.
<img alt="Figure1" src="/files/ftp_upload/13085/13085_PT_Figure_1.svg" style="text-align: center; height: 56px;" />
The reaction facilitates a two-step conversion of haloalkanes to carboxylic acids. Here, haloalkanes are first converted to nitriles using sodium cyanide via an SN2 reaction. The resultant nitrile is then hydrolyzed to yield carboxylic acids bearing one more carbon than the haloalkane used. The reaction uses dimethyl sulfoxide, alcohols, or water as solvents. As the process involves the SN2 mechanism, tertiary alkyl halides are seldom used.
<img alt="Figure2" src="/files/ftp_upload/13085/13085_PT_Figure_2.svg" style="text-align: center; height: 46px;" />

Karboksilik asitlerin hazırlanması: nitrillerin hidrolizi

Nitriles (R&#8211;CN) can be converted into carboxylic acids (R&#8211;COOH) upon treatment with aqueous acids, i.e., upon hydrolysis of nitriles. Under ...

Karboksilik Asitler

Acid Halides to Carboxylic Acids: Hydrolysis

Hydrolysis of acid halides is a nucleophilic acyl substitution reaction in which acid halides react with water to give carboxylic acids. The reaction occurs readily and does not require acid or a base catalyst.
As shown below, the mechanism involves a nucleophilic attack by water at the carbonyl carbon to form a tetrahedral intermediate. This is followed by the reformation of the carbon&#8211;oxygen &#960; bond along with the departure of a halide ion. A final proton transfer step yields carboxylic acid as the substitution product.&#160;
<img alt="Figure1" src="/files/ftp_upload/12361/12361_PT_Figure_1_.svg" style="text-align: center; height: 200px;" />
The reaction produces a very strong acid, HCl, as a by-product. Therefore, a base such as pyridine is used in the reaction, which reacts with HCl to form pyridinium chloride. This process neutralizes the acid and prevents undesired side reactions.

Asit Halojenürlerden Karboksilik Asitlere: Hidroliz

Hydrolysis of acid halides is a nucleophilic acyl substitution reaction in which acid halides react with water to give carboxylic acids. The reaction ...

Karboksilit Asit Türevleri

Protecting Groups for Aldehydes and Ketones: Introduction

Protecting groups are compounds that can bind to a specific functional group in the presence of other functional groups to protect them from undesired chemical reactions. These compounds can selectively bind to particular functional groups and advance chemoselective reactions in polyfunctional systems (Figure 1). After the functional group has served its purpose, it is removed by reacting it with specific compounds.
<img alt="Figure1" src="/files/ftp_upload/12844/12844_PT_Figure_1.svg" style="text-align: center; height: 60px;" />
The aldehydes and ketones can be selectively protected in the presence of other carbonyl groups such as esters or acids based upon their reactivity. This is important for the manipulation of one functional group over the other.
For instance, when carrying out a reduction reaction in the presence of an ester and a ketone, the ketone will always be preferentially reduced to alcohol. In order to achieve the selective reduction of an ester to an alcohol while keeping the ketone unaffected, the ketone group needs to be protected (Figure 2, first step). After the ketone is protected, the ester is reduced to an alcohol using LiAlH4 (Figure 2, second step). Finally, the ketone is regenerated by removing the protecting group (Figure 2, third step).
<img alt="Figure2" src="/files/ftp_upload/12844/12844_PT_Figure_2.svg" style="text-align: center; height: 215px;" />
Acetals and thioacetals are the most commonly used protecting groups for aldehydes and ketones and can be easily removed. In addition, they are resistant to chemical species such as nucleophiles, or reducing and oxidizing agents.

Aldehitler ve Ketonlar için Koruma Grupları: Giriş

Protecting groups are compounds that can bind to a specific functional group in the presence of other functional groups to protect them from undesired ...

Aldehitler ve Ketonlar

Acetals and Thioacetals as Protecting Groups for Aldehydes and Ketones

Acetals are formed by reacting two equivalents of alcohol with carbonyl compounds like aldehydes or ketones. Acetals are unaffected by bases, nucleophiles, oxidizing agents, and reducing agents. They serve as protecting groups for aldehydes and ketones. Acetals can be easily formed and also easily removed via mild acid hydrolysis.
In the presence of multiple functional groups, when selective reduction of one group over the other is desired, groups like aldehydes and ketones that form acetals readily can be protected from undergoing undesirable reactions. For instance, if a compound contains a ketone and an ester group, the ketone can be protected by converting it into acetal. On the other hand, the ester does not form acetal; hence it can be subjected to the desired reaction, and in&#160;the end, the ketone can be deprotected.
<img alt="Figure1" src="/files/ftp_upload/12333/12333_Figure_1.svg" style="opacity: 0.9; text-align: center; height: 200px;" />
The sulfur-containing analogs of acetals are called thioacetals that&#160;can act as an efficient protecting group for aldehydes and ketones. The thioacetals are stable in acidic conditions. Due to this, they cannot be deprotected by acid hydrolysis. Instead, mercuric chloride in aqueous acetonitrile is used for its deprotection.
<img alt="Figure2" src="/files/ftp_upload/12333/12333_Figure_2.svg" style="text-align: center; height: 55px;" />
Apart from acting as protecting groups, thioacetals also play a major role in organic synthesis, especially in reduction reactions. Thioacetals can undergo desulfurization in the presence of Raney nickel and hydrogen to form hydrocarbons.
<img alt="Figure3" src="/files/ftp_upload/12333/12333_Figure_3.svg" style="text-align: center; height: 55px;" />

Aldehitler ve ketonlar için koruyucu gruplar olarak asetaller ve tiyoasetaller

Acetals are formed by reacting two equivalents of alcohol with carbonyl compounds like aldehydes or ketones. Acetals are unaffected by bases, ...

Amides to Carboxylic Acids: Hydrolysis

Amides can undergo either acid-catalyzed hydrolysis or base-promoted hydrolysis through a typical nucleophilic acyl substitution. Each hydrolysis requires severe conditions.
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more electrophilic. Next, water acts as a nucleophile and attacks the carbonyl carbon to form a tetrahedral intermediate. Further, deprotonation of the tetrahedral intermediate gives a neutral tetrahedral addition intermediate. Subsequent protonation of the amino nitrogen converts the amino group into a better leaving group. In the next step, the carbonyl group is re-formed with the departure of ammonia as a leaving group. A final deprotonation step yields a carboxylic acid.
<img alt="Figure1" src="/files/ftp_upload/12372/12372_PT_Figure_1_.svg" style="text-align: center; height: 225px;" />
The formation of ammonium ion drives the equilibrium favoring the product formation.
Base-promoted hydrolysis: 
Base-promoted hydrolysis is another nucleophilic acyl substitution reaction, where hydroxide acts as a nucleophile. Amides undergo hydrolysis when heated under basic aqueous solutions to produce carboxylic acid.
The base-promoted mechanism involves a nucleophilic attack by the hydroxide ion at the amide carbonyl carbon to form a tetrahedral intermediate. In the second step, the carbonyl group is reconstructed with the departure of an amide ion as a leaving group. Next, deprotonation yields a carboxylate ion and ammonia. This step drives the reaction to completion, which pushes the equilibrium towards the product. A final step involves acidification of the carboxylate ion to give free acid.
<img alt="Figure2" src="/files/ftp_upload/12372/12372_PT_Figure_2.svg" style="text-align: center; height: 200px;" />

Amidlerden Karboksilik Asitlere: Hidroliz

Amides can undergo either acid-catalyzed hydrolysis or base-promoted hydrolysis through a typical nucleophilic acyl substitution. Each hydrolysis requires ...