Biz bu çalışmaları desteklemek amacıyla Stony Brook New York Eyalet Üniversitesi&#39;nden cömert start-up fonları kabul. Biz de Togni reaktifi II sentezi için bize TMSCF 3 reaktifi sağlamak için TOSOH F-Tech, Inc. teşekkür ederim.

1. Ön ürün hazırlanması: Metil 4- (N -hydroxyacetamido) benzoat (1a) sentezi <ol><li> Metil 4-nitrobenzoat azaltılması. <ol><li> Bir fırında kurutulmuş 250 ml&#39;lik iki halinde metil 4-nitrobenzoat (27.6 mmol, 1.00 eşdeğer), karbon üzerinde% 5 Rodyum 159 mg (Rh / C, 0,300 mol,% Rh) ve bir manyetik karıştırma çubuğu-5,00 g ekleme (18 saat 150 ° C &#39;de kurutulmuş) boyunlu yuvarlak dipli bir reaksiyon kabı. Not: Reaktifler çevre atmosferi altında tartıldı edilebilir. Bununla birlikte, reaksiyon, azot atmosferi altında gerçekleştirilebilir gerekmektedir. </li><li> Bir azot / vakum manifolduna şişenin bir boynuna bağlanmak ve bir septum ile diğer boyun kap. Üç vakum dolum döngüleri gerçekleştirin (örneğin, şişenin havasını pompalama ve azot gazı ile sonuçlanan vakum değiştirme) azot gazı ile şişe içinde havayı değiştirmek için. </li><li> Hava geçirmez şırınga kullanılarak reaksiyon balonuna 138 mi susuz tetrahidrofuran (THF, 0.200 M) ekleyin. Serin ve reaksiyon Mixt karıştırın15 dakika boyunca 0 ° C&#39;de ure. </li><li> Hava geçirmez bir şırınga ile, 0 ° C&#39;de, reaksiyon karışımına hidrazin monohidrat 1,47 ml (1,52 g, 30,4 mmol, 1.20 eşdeğer) damla damla ekleyin. Bir ince tabaka kromatografisi (TLC) ile reaksiyonu izleyin. Heksanlar kullanarak: etil asetat (EtOAc) (4: 1 v / v, Rf = 0.23) yıkama sıvısı olarak tlc geliştirmektir. </li><li> Metil 4-nitrobenzoat tamamen tüketildiğinde, vakumla süzme kullanılarak Buchner hunisi hammadde karışımı 60 ml silisli toprak pedinden (yani, Celite, 5 g) ile reaksiyon karışımı filtre edilir. EtOAc ile filtre (20 ml x 3 defa) yıkanır. Daha fazla saflaştırılmadan direkt olarak kullanılan ham metil 4- (N -hydroxyamino) benzoat vermek üzere bir döner buharlaştırıcı kullanılarak vakum altında Filtrat konsantre edilir. </li></ol></li><li> Metil 4- (N -hydroxyamino) benzoat asetil koruma <ol><li> Sodyum bikarbonat, 2.55 g ekleme (NaHCO3, 30.4 mmol, 1.20 eşdeğer), tüm hamönceki aşamada elde edilen metil 4- (N -hydroxyamino) benzoat, ve fırında kurutulmuş 500 ml&#39;lik iki boyunlu yuvarlak tabanlı bir şişeye bir karıştırma çubuğu. </li><li> Bir septum ile tek boyun kap ve bir azot / vakum manifolduna başka boyun bağlayın. Azot gazı ile şişe içinde havayı değiştirmek için üç vakum dolum döngüleri gerçekleştirin. </li><li> Hava geçirmez bir şırınga kullanılarak reaksiyon balonuna 138 ml susuz dietil eter (Et 2, O, 0,200 M) ekleyin. Serin ve 15 dakika boyunca 0 ° C&#39;de, reaksiyon karışımı karıştırılmıştır. </li><li> Susuz Et 2 O (138 mi, 0,220 M) (2.17 mL, 2.39 g, 30.4 mmol, 1.20 eşdeğer) asetil klorit ihtiva eden bir çözelti hazırlayın. 10,0 ml / st bir oranda bir şırınga pompası kullanılarak, 0 ° C de, reaksiyon karışımına solüsyonu ekleyin. </li><li> İlave etme işleminin sonunda, bir silisli toprak pedinden geçirilerek karışımı filtre Reaksiyon (yani, Celite, 5 g), 60 ml vakumla süzme kullanılarak Buchner hunisi hammadde karışımı. EtOAc ile filtre (20 ml x 3 defa) yıkanır. KonsantreBir döner buharlaştırıcı kullanılarak vakum altında filtre ürünü. </li><li> Heksan ile flaş kolon kromatografisiyle 35 tasfiye ile ham ürün arıtın: EtOAc (4: 1 ila 1: 1 (v / v)) (Rf = 0.13, heksanlar: EtOAc (4: 1 (v / v)) 5.31 elde Açık sarı bir katı (25.4 mmol,% 92 verim) halinde metil 4- (N -hydroxyacetamido) benzoat örn. </li></ol></li></ol> Benzoat (2a) - Metil 4- ((triflorometoksi) asetamido N) Sentezi 2. <ol><li> , Metil 4- (N -hydroxyacetamido) benzoat (1a) (9.56 mmol, 1.00 eşdeğer) 2.00 g, Cs 2 CO 3 311 mg (0,956 mmol, 10.0 mol%), Togni II reajanı 3.63 g (11.5 mmol ekleme 1,20 eşdeğer) ve torpido gözü (nitrojen atmosferi içinde bir fırında kurutulmuş 250 ml&#39;lik yuvarlak dipli bir şişeye bir manyetik karıştırma çubuğu). NOT: Bu reaksiyon, eldiven kutusu dışında Schlenk teknikleri kullanılarak gerçekleştirilebilir. Dikkat: Saf Togni reaktif II darbe ve sürtünme duyarlı, açık alevs, kıvılcım ve / veya taşlama kaçınılmalıdır. Yumuşak ve perdahlı araçlar manipülasyon için kullanılmalıdır. Buna ek olarak, reaksiyon karışımı, bir emniyet koruma kalkanının ardında karıştırılır. 36 </li><li> Reaksiyon şişesine, kurutuldu ve gazı alınmış kloroform 95,6 ml (CHCI3, 0,100 M) ekleyin. </li><li> Septum ile şişesi Cap içeri veya 16 saat süre ile eldiven kutusu dışında da, N2 atmosferi altında, 23 ° C&#39;de, reaksiyon karışımı karıştırılmıştır. </li><li> Herhangi bir katı artık maddeyi çıkarmak için bir filtre hunisi içinden, reaksiyon karışımı filtre. Bir döner buharlaştırıcı kullanılarak vakum altında Filtrat konsantre edilir. </li><li> Diklorometan (CH2C! 2) flaş kolon kromatografisi heksanlar ile yıkanarak ham ürün arıtın (7: 3-0: 1 (v / v)) (Rf = 0.44 (CH2C! 2) elde etmek için (- (Triflorometoksi) asetamido K) benzoat (9.05 mmol,% 95 verim) metil 4- 2,51 g. NOT: Togni reaktif II hazırlanan anlaşma olduğunuliteratür prosedürlerine 37 ve -35 ° C&#39;de torpido gözü dondurucuda saklanan ing uzun bir süre boyunca kalitesini korumak için. Bu reaksiyon, oksijen duyarlıdır. Tüm reaktifler, oda sıcaklığında, ortam atmosferi altında tartıldı de, reaksiyon kabından oksijenin uzaklaştırılması önemlidir. Kurutulmuş ve dondurularak-Pompalama-Eritme prosedürü üç döngü yapmayı takiben nitrojen atmosferi altında CaH 2 onu damıtılması ile hazırlanır CHCI3 gazı alındı. </li></ol> 3. Metil sentezi 4-Asetamido-3- (triflorometoksi) benzoat OCF3 -migration (3a) ile <ol><li> 50 ml&#39;lik bir basınç aracı içine ve benzoat (9.05 mmol, 1.0 eşdeğer), bir manyetik karıştırma çubuğu-ve Meno 2 (1.00 M) 9,05 ml - 2.51 g metil 4- ((triflorometoksi) asetamido N) eklenir. Bir vidalı başlık ile kap Cap. </li><li> 20 saat emniyet korumalı arkasına 120 ° C&#39;de, reaksiyon karışımı karıştırılır. Dikkat: Saf olmayan nitrometanPatlayıcı, yani, reaksiyon karışımı, güvenlik koruma kalkanının ardında karıştırılmalıdır. </li><li> Oda sıcaklığında tepkisel karışımın soğutun. </li><li> Bir 100 ml&#39;lik yuvarlak dipli bir şişeye, reaksiyon karışımı aktarın. </li><li> Bir döner buharlaştırıcı kullanılarak vakum altında reaksiyon karışımının konsantre edin. </li><li> Flaş kolon kromatografisi heksan ile yıkanarak ham ürün arıtın: EtOAc (9: 1 ila 7: 3 (v / v)) (Rf = 0.51 heksan: EtOAc (4: 1 (v / v)) elde Metil 4-asetamido-3- (triflorometoksi) benzoat 2.13 g (7.69 mmol,% 85). NOT: Bu reaksiyon, ortam atmosfer altında gerçekleştirilebilir. Azot atmosferi gerekli değildir. Bir su yoğunlaştıncısı ile donatılmış yuvarlak dipli bir reaksiyon kabı alternatif bir reaksiyon aygıtı olarak kullanılabilir. </li></ol> Yeni Ürünler 4. Karakterizasyonu <ol><li> 1 H, 13C-NMR spektroskopisi ve yüksek rezolüsyonlu kütle spektroskopisi yoluyla bu yeni bileşiklerin karakterize ve 19F NMR spektroskopisi kullanımıflor atomu ihtiva eden bileşikleri tanımlamak için. 34 </li></ol>

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C., Kahn, M., Mitra, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rapid+chromatographic+technique+for+preparative+separations+with+moderate+Resolution.">Rapid chromatographic technique for preparative separations with moderate Resolution.</a> J. Org. Chem. 43, 2923-2925 (1978).</li><li>Fiederling, N., Haller, J., Schramm, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Notification+about+the+Explosive+Properties+of+Togni's+Reagent+II+and+One+of+Its+Precursors.">Notification about the Explosive Properties of Togni's Reagent II and One of Its Precursors.</a> Org. Process Res. Dev. 17, 318-319 (2013).</li><li>Matousek, V., Pietrasiak, E., Schwenk, R., Togni, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=One-pot+synthesis+of+hypervalent+iodine+reagents+for+electrophilic+trifluoromethylation.">One-pot synthesis of hypervalent iodine reagents for electrophilic trifluoromethylation.</a> J. Org. Chem. 78, 6763-6768 (2013).</li></ol>

The authors declare no competing financial interests.

Nedeniyle trifluoromethoxylated arenlerin sentezi için genel ve kullanıcı dostu bir prosedürün olmaması, pek çok OCF 3-ihtiva eden aromatik bileşikler, son derece pahalıdır. 34 Stratejimiz geniş bir fonksiyonel grup toleransı değiştirir ve çeşitli trifluoromethoxylated arenler için kolay bir erişim sağlar. Bu bileşikler, yeni farmasotikler, ziraat kimyasalları, ve malzemelerin keşfi ve geliştirilmesi için değerli yapı taşları hizmet edebilir. ...

Triflorometoksi (OCF3) grubu yüksek olması nedeniyle elektronegatiflik eşsiz kombinasyonu 1935 2 triflorometil eter ilk sentez beri hayatı ve malzeme bilimi araştırma üzerinde derin bir etkisi yapmıştır (χ = 3.7) 3 ve mükemmel lipofilisite (Π x = 1.04), 4 triflorometoksi grubu tıp, tarım ve malzemeleri sektöründe geniş uygulama bulmuştur. 5-10 Bununla birlikte, organik moleküllerin, özellikle aromatik bileşikler, içine OCF3 grubunun uyduruk giriş sentetik kimyada önemli bir sorun olmaya devam etmektedir. Son birkaç yıldır, bu engeli aşmak için çabalar trifluoromethoxylated arenlerin sentezi için dönüşümlerin bir avuç gelişmesine yol açmıştır 5-7,9-11 triklorine öncüleri üzerindeki Bunlar (i) klor / flor değişimi;. 1,12 fluoroformates -17 (ii) deoxyfluorination; 18 </sup&gt; (iii) oksidatif fluorodesulfurization; 19-21 (iv) alkollerin elektrofilik trifluorometilasyon, 22-25 (v) nükleofilik trifluoromethoxylation, 26-30, aril boratlar ve stannanlarla (vi) geçiş metali aracılı trifluoromethoxylation, 31 ve (vii ) radikali trifluoromethoxylation. 32,33 Bununla birlikte, bu yaklaşımların pek çoğu, ya düşük alt-tabaka kapsamından muzdarip ya da son derece zehirli ve / veya termal olarak kararsız reaktiflerin kullanılmasını gerektirir. Dolayısıyla, OCF3-ihtiva eden bileşiklerin sentezi için genel ve kullanıcı dostu bir yöntem olmaması nedeniyle, OCF3 grubunun potansiyeli tam olarak kimya istismar edilmemiştir. Trifluoromethoxylation reaksiyonlarında eden ilgi bir parçası olarak, 34 Biz metil 4-asetamido-3- (trifluorometoksi sentezi için bu tarifnamede, bir, iki aşamalı bir protokol (örneğin, radikalidir -trifluoromethylation ve ısının neden olduğu OCF3 -migration) tarifmetil 4- (N -hydroxyacetamido) benzoat (1a) benzoat (3a)). Strateji orto -trifluoromethoxylated anilin türevlerinin geniş bir sentezi için-yapmaktadır kolay ve uygulanabilir.

<table><tbody><tr><td>5% Rhodium on carbon</td><td>Aspira Scientific</td><td>300835</td><td>5% wt% dry loading</td></tr><tr><td>Hydrazine monohydrate</td><td>Sigma-Alderich</td><td>13696HMV</td><td>Reagent grade, 98%</td></tr><tr><td>Acetyl chloride</td><td>Alfa Aesar</td><td>10176887</td><td>98%</td></tr><tr><td>Sodium bicarbonate</td><td>Fisher Scientific</td><td>134826</td><td>Chemical pure</td></tr><tr><td>Cesium carbonate</td><td>Alfa Aesar</td><td>12887</td><td>99.9%, metals basis</td></tr><tr><td>Togni Reagent II</td><td></td><td></td><td>Prepared according to the literature procedure (ref 37). Caution: Pure Togni reagent II is impact and friction sensitive, treat it with great care (see ref. 36).</td></tr><tr><td>Tetrahydrofuran</td><td>BDH</td><td>BDH1149-4LG</td><td>Distilled from deep purple sodium benzophenone ketyl.</td></tr><tr><td>Diethyl Ether</td><td>Fisher Scientific</td><td>148221</td><td>Distilled from deep purple sodium benzophenone ketyl.</td></tr><tr><td>Chloroform</td><td>Fisher Scientific</td><td>141739</td><td>Dried over CaH&lt;sub&gt;2&lt;/sub&gt; and distilled</td></tr><tr><td>Nitromethane</td><td>Alfa Aesar</td><td>J03z053</td><td>Dried over CaSO&lt;sub&gt;4&lt;/sub&gt; and distilled</td></tr><tr><td>Silica gel</td><td>SILICYCLE</td><td>60514</td><td>40-63 &amp;micro;m (230-400 mesh)</td></tr><tr><td>Celite</td><td>EMD</td><td>2012040674</td><td>Not acid washed</td></tr></tbody></table>

protocol for the synthesis of ortho-trifluoromethoxylated aniline derivatives

Triflorometoksi (OCF3) grubu taşıyan moleküller genellikle farmakolojik ve biyolojik özellikleri, istenen göstermektedir. Ancak, trifluoromethoxylated aromatik bileşiklerin sentezi uyduruk organik sentez içinde zorlu bir sorun olmaya devam etmektedir. Konvansiyonel yaklaşımlar genellikle kötü substrat kapsam muzdarip ya da yüksek derecede toksik, zor kolu kullanımını gerektiren ve / veya termal olarak kararsız reaktifler. Burada, kullanılarak metil 4-asetamido-3- (triflorometoksi) benzoat sentezi için kullanıcı dostu bir protokol rapor 1-triflorometil-1,2-benziodoksol-3 (1H) -on (Togni reaktifi II). Sezyum karbonat katalitik bir miktarının varlığında Togni II reajanı ile metil 4- (N -hydroxyacetamido) benzoat (1a) tedavisi (Cs 2 CO 3) oda sıcaklığında kloroform içinde metil 4- elde (N - (triflorometoksi) asetamido) benzoat (2a). Bu ara madde daha sonra son ürün metil 4-asetamido-3- (triflorometil ile dönüştürüldü120 ° C&#39;de, nitrometan toksı) benzoat (3a). Bu prosedür, genel olarak ve yeni ilaç, ziraat kimyasalları ve fonksiyonel maddelerin keşfi ve geliştirilmesi için yararlı sentetik yapı blokları hizmet verebilir orto -trifluoromethoxylated anilin türevlerinin geniş bir spektrumunun sentezine de uygulanabilir.

Metil 4- (N -hydroxyacetamido) benzoat (1a), yani, bir katalizör olarak% 5 Rh / C kullanılarak hidrazin ile metil 4-nitrobenzoat indirgeme metil 4- (oluşturulması için (iki aşamalı bir prosedür ile% 92 izole edilmiş verimle sentezlendi N -hydroxyamino) benzoat elde edilen hidroksilamin asetil koruma ile). sezyum karbonat katalitik bir miktarının varlığında Togni II reajanı ile 1a O- trifluorometilasyon (...

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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Sentezi İçin Protokol<em&gt; Ortho</em&gt; -trifluoromethoxylated Anilin türevleri

An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of ...

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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

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9.9K Görüntüleme.  State University of New York at Stony Brook. An operationally simple procedure for the synthesis of ortho-trifluoromethoxylated aniline derivatives via a two-step sequence of O-trifluoromethylation of N-aryl-N-hydroxyacetamide followed by thermally induced intramolecular OCF3-migration is reported.

Video: Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

Synthesis of Hypervalent Iodonium Alkynyl Triflates for the Application of Generating Cyanocarbenes

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent reactions with azides to form cyanocarbene intermediates. The synthesis of hypervalent iodonium alkynyl triflates can be facile, but difficulties stem from their isolation and reactivity. In particular, the necessity to use filtration under inert atmosphere at -45 &deg;C for some HIATs requires special care and equipment. Once isolated, the compounds can be stored and used in reactions with azides to form cyanocarbene intermediates. 
The evidence for cyanocarbene generation is shown by visible extrusion of dinitrogen as well as the characterization of products that occur from O-H insertion, sulfoxide complexation, and cyclopropanation. A side reaction of the cyanocarbene formation is the generation of a vinylidene-carbene and the conditions to control this process are discussed. There is also potential to form a hypervalent iodonium alkenyl triflate and the means of isolation and control of its generation are provided. The O-H insertion reaction involves using a HIAT, sodium azide or tetrabutylammonium azide, and methanol as solvent/substrate. The sulfoxide complexation reaction uses a HIAT, sodium azide or tetrabutylammonium azide, and dimethyl sulfoxide as solvent. The cyclopropanations can be performed with or without the use of solvent. The azide source must be tetrabutylammonium azide and the substrate shown is styrene.

Herein is described the synthesis, isolation, and reactions of hypervalent iodonium alkynyl triflates (HIATs) with azides to generate cyanocarbenes. The procedures will involve air-sensitive and cryogen techniques, including cold filtration under an inert atmosphere. Handling and safety of the synthesized compounds will also be discussed.

Yaratma Cyanocarbenes Uygulanması için hipervalent iyodonyum Alkınıl triflatların Sentezi

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent ...

Kimya

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors

The guanidine group is one of the most important pharmacophoric groups in medicinal chemistry. The only amino acid carrying a guanidine group is arginine. In this article, an easy method for the modification of the guanidine group in peptidic ligands is provided, with an example of RGD-binding integrin ligands. It was recently demonstrated that the distinct modification of the guanidine group in these ligands allows for the selective modulation of the subtype (e.g., between the subtypes &#945;v and &#945;5). Moreover, a formerly unknown strategy for the functionalization via the guanidine group was demonstrated, and the synthetic approach is reviewed in this document. The modifications described here involve terminally (N&#969;) alkylated and acetylated guanidine groups. For the synthesis, tailor-made precursor molecules are synthesized, which are then subjected to a reaction with an orthogonally deprotected amine to transfer the pre-modified guanidine group. For the synthesis of alkylated guanidines, precursors based on N,N&#8242;-Di-Boc-1H-pyrazole-1-carboxamidine are used to synthesize acylated compounds, the precursor of choice being a correspondingly acylated derivative of N-Boc-S-methylisothiourea, which can be obtained in one- and two-step reactions.

A protocol for the synthesis of alkyl-modified guanidines based on the use of the corresponding precursors is presented.

Kişiye özel Prekürsorler tarafından Modifikasyon ve Guanidin Grubu işlevselleştirilmesi

The guanidine group is one of the most important pharmacophoric groups in medicinal chemistry. The only amino acid carrying a guanidine group is arginine. ...

Biyokimya

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)

The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order to streamline synthesis by saving steps, time and material compared to conventional methods that require the introduction and removal of activating or directing groups. Therefore, the functionalization of C-H bonds is also attractive for green chemistry. Under oxidative conditions, two C-H bonds or one C-H and one heteroatom-H bond can be transformed to C-C and C-heteroatom bonds, respectively. Often these oxidative coupling reactions require synthetic oxidants, expensive catalysts or high temperatures. Here, we describe a two-step procedure to functionalize indole derivatives, more specifically tetrahydrocarbazoles, by C-H amination using only elemental oxygen as oxidant. The reaction uses the principle of C-H functionalization via Intermediate PeroxideS (CHIPS). In the first step, a hydroperoxide is generated oxidatively using visible light, a photosensitizer and elemental oxygen. In the second step, the N-nucleophile, an aniline, is introduced by Br&#248;nsted-acid catalyzed activation of the hydroperoxide leaving group. The products of the first and second step often precipitate and can be conveniently filtered off. The synthesis of a biologically active compound is shown.

Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides CHIPS

A two-step procedure for the synthesis of pharmaceutically active indole-derivatives by C-H functionalization with anilines is described, using photo- and Br&#248;nsted acid catalysis.

Intermediate Peroksitlerin yoluyla fotokimyasal ve Asit-katalize CH fonksiyonlandırmalar tarafından Antiviral tetrahidrokarbazole Türevlerinin Sentezi (CİPS)

The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order ...

Synthesis of Indoxyl-glycosides for Detection of Glycosidase Activities

Indoxyl glycosides proved to be valuable and versatile tools for monitoring glycosidase activities. Indoxyls are released by enzymatic hydrolysis and are rapidly oxidized, for example by atmospheric oxygen, to indigo type dyes. This reaction enables fast and easy screening in vivo without isolation or purification of enzymes, as well as rapid tests on agar plates or in solution (e.g., blue-white screening, micro-wells) and is used in biochemistry, histochemistry, bacteriology and molecular biology. Unfortunately the synthesis of such substrates proved to be difficult, due to various side reactions and the low reactivity of the indoxyl hydroxyl function. Especially for glucose type structures low yields were observed. Our novel approach employs indoxylic acid ester as key intermediates. Indoxylic acid esters with varied substitution patterns were prepared on scalable pathways. Phase transfer glycosylations with those acceptors and peracetylated glycosyl halides can be performed under common conditions in high yields. Ester cleavage and subsequent mild silver mediated glycosylation yields the peracetylated indoxyl glycosides in high yields. Finally deprotection is performed according to Zempl&#233;n.

Indoxyl glycosides are well-established and widely used tools for enzyme screening and enzyme activity monitoring. Especially for glucose type structures previous syntheses proved to be challenging and low yielding. Our novel approach employs indoxylic acid esters as precious intermediates to yield a considerable number of indoxyl glycosides in good yields.

Glikosidaz Faaliyetlerinin Belirlenmesi için indoksil-glikozitler sentezi

Indoxyl glycosides proved to be valuable and versatile tools for monitoring glycosidase activities. Indoxyls are released by enzymatic hydrolysis and are ...

Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile N-(2-alkoxyvinyl)sulfonamides, which react under a variety of conditions to afford useful N- and O-containing compounds. Acid-catalyzed addition of alcohols or thiols to N-(2-alkoxyvinyl)sulfonamide-containing phthalans provides access to ketals and thioketals, respectively. Selective reduction of the vinyl group in N-(2-alkoxyvinyl)sulfonamide-containing phthalans via hydrogenation yields the corresponding phthalan in good yield, whereas reduction with sodium bis(2-methoxyethoxy)aluminumhydride generates a ring-opened phenethylamine analogue. Because the N-(2-alkoxyvinyl)sulfonamide functional group is synthetically versatile, but often hydrolytically unstable, this protocol emphasizes key techniques in preparing, handling, and reacting these pivotal substrates in several useful transformations.

Preparation of N-2-alkoxyvinylsulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Representative experimental procedures for the synthesis of N-(2-alkoxyvinyl)sulfonamides and subsequent conversion to phthalan and phenethylamine derivatives are presented in detail.

Nhazırlanması-(2-alkoxyvinyl) N- tosyl-1,2,3-triazoles ve yerine Phthalans ve fenitilaminler sonraki dönüşüm sülfonamidler

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile ...

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and 1-methyl-4-(1,2,2-triiodovinyl)benzene as representative examples for the practical chemoselective preparation of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes from the chemoselective iodination of terminal alkynes mediated by hypervalent-iodine reagents. The chemoselectivity was confirmed by using p-tolylethyne as a model substrate to screen a variety of iodine sources and/or the hypervalent-iodine reagents. A combination of tetrabutylammonium iodide (TBAI) and (diacetoxyiodo)benzene (PIDA) selectively generates 1-iodoalkynes, while a combination of KI and PIDA generates 1,2-diiodoalkenes. A one-pot synthesis based on both TBAI-PIDA and KI-PIDA yields the corresponding 1,1,2-triiodoalkenes. These protocols were subsequently applied to the synthesis of synthetically important aromatic and aliphatic 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes, which were obtained in good yield with excellent chemoselectivity.

Herein, detailed protocols for the oxidative iodination of terminal alkynes using hypervalent-iodine reagents are presented, which chemoselectively afford 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes.

1-Iodoalkynes, 1,2-Diiodoalkenes ve 1,1,2-Triiodoalkenes Terminal Alkynes oksidatif iyodinasyon üzerinde dayalı Chemoselective hazırlanması

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and ...

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates

Maleimide-bearing bifunctional probes have been employed for decades for the site-selective modification of thiols in biomolecules, especially antibodies. Yet maleimide-based conjugates display limited stability in vivo because the succinimidyl thioether linkage can undergo a retro-Michael reaction. This, of course, can lead to the release of the radioactive payload or its exchange with thiol-bearing biomolecules in circulation. Both of these processes can produce elevated activity concentrations in healthy organs as well as decreased activity concentrations in target tissues, resulting in reduced imaging contrast and lower therapeutic ratios. In 2018, we reported the creation of a modular, stable, and easily accessible phenyloxadiazolyl methyl sulfone reagent &#8212; dubbed &#8216;PODS&#8217; &#8212; as a platform for thiol-based bioconjugations. We have clearly demonstrated that PODS-based site-selective bioconjugations reproducibly and robustly create homogenous, well-defined, highly immunoreactive, and highly stable radioimmunoconjugates. Furthermore, preclinical experiments in murine models of colorectal cancer have shown that these site-selectively labeled radioimmunoconjugates exhibit far superior in vivo performance compared to radiolabeled antibodies synthesized via maleimide-based conjugations. In this protocol, we will describe the four-step synthesis of PODS, the creation of a bifunctional PODS-bearing variant of the ubiquitous chelator DOTA (PODS-DOTA), and the conjugation of PODS-DOTA to the HER2-targeting antibody trastuzumab.

In this protocol, we will describe the synthesis of PODS, a phenyoxadiazolyl methyl sulfone-based reagent for the site-selective attachment of cargos to the thiols of biomolecules, particularly antibodies. In addition, we will describe the synthesis and characterization of a PODS-bearing bifunctional chelator and its conjugation to a model antibody.

Sentez ve Site seçici olarak oluşturulması için Thiol reaktif reaktif Bioconjugation Immunoconjugates modifiye

Maleimide-bearing bifunctional probes have been employed for decades for the site-selective modification of thiols in biomolecules, especially antibodies. ...

Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyl(tropone)iron

aza-Michael adducts of tricarbonyl(tropone)iron are synthesized by two different methods. Primary aliphatic amines and cyclic secondary amines participate in a direct aza-Michael reaction with tricarbonyl(tropone)iron under solvent-free conditions. Less nucleophilic aniline derivatives and more hindered secondary amines add efficiently to the cationic tropone complex formed by protonation of tricarbonyl(tropone)iron. While the protocol utilizing the cationic complex is less efficient overall for accessing the aza-Michael adducts than the direct, solvent-free addition to the neutral complex, it allows the use of a broader range of amine nucleophiles. Following protection of the amine of the aza-Michael adduct as a tert-butyl carbamate, the diene is decomplexed from the iron tricarbonyl fragment upon treatment with cerium(IV) ammonium nitrate to provide derivatives of 6-aminocyclohepta-2,4-dien-1-one. These products can serve as precursors to diverse compounds containing a seven-membered carbocyclic ring. Because the demetallation requires protection of the amine as a carbamate, the aza-Michael adducts of secondary amines cannot be decomplexed using the protocol described here.

Preparation of 6-aminocyclohepta-2,4-dien-1-one Derivatives via Tricarbonyltroponeiron

Representative experimental procedures for the addition of amine nucleophiles to tricarbonyl(tropone)iron and subsequent demetallation of the resulting complexes are presented in detail.

Trikarbonil(tropon) demir ilerbulu 6-aminosiklohepta-2,4-dien-1-bir Türevlerinin hazırlanması

aza-Michael adducts of tricarbonyl(tropone)iron are synthesized by two different methods. Primary aliphatic amines and cyclic secondary amines participate ...

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

We introduced a regioselective and atom-economical procedure for the synthesis of 3-substituted indoles by annulation of nitrosoarenes with ethynyl ketones. The reactions were carried out achieving indoles without any catalyst and with excellent regioselectivity. No traces of 2-aroylindole products were detected. Working with 4-nitronitrosobenzene as starting material, the 3-aroyl-N-hydroxy-5-nitroindole products precipitated from the reaction mixtures and were isolated by filtration without any further purification technique. Differently from the corresponding N-hydroxy-3-aryl indoles that, spontaneously in solution, give dehydrodimerization products, the N-hydroxy-3-aroyl indoles are stable and no dimerization compounds were observed.

A Direct, Regioselective and Atom-Economical Synthesis of 3-Aroyl-N-hydroxy-5-nitroindoles by Cycloaddition of 4-Nitronitrosobenzene with Alkynones

3-Aroyl-N-hydroxy-5-nitroindoles were synthesized by cycloaddition of 4-nitronitrosobenzene with a conjugated terminal alkynone in a one-step thermal procedure. Preparation of the nitrosoarene and of the alkynones were adequately reported and respectively through oxidation procedures on the corresponding aniline and on the alkynol.

Alkiyonları ile 4-Nitronitrosobenzene Sikloaddition tarafından 3-Aroyl- N-hidroksi-5-nitroinollerin Direkt, Regiosel ve Atom-Ekonomik Sentezi

We introduced a regioselective and atom-economical procedure for the synthesis of 3-substituted indoles by annulation of nitrosoarenes with ethynyl ...

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach

Methine-bridged conjugated bicyclic aromatic compounds are common constituents of a range of biologically relevant molecules such as porphyrins, dipyrrinones, and pharmaceuticals. Additionally, restricted rotation of these systems often results in highly to moderately fluorescent systems as observed in 3H,5H-dipyrrolo[1,2-c:2',1'-f]pyrimidin-3-ones, xanthoglows, pyrroloindolizinedione analogs, BODIPY analogs, and the phenolic and imidazolinone ring systems of Green Fluorescent Protein (GFP). This manuscript describes an inexpensive and operationally simple method of performing a Claisen-Schmidt condensation to generate a series of fluorescent pH dependent pyrazole/imidazole/isoindolone dipyrrinone analogs. While the methodology illustrates the synthesis of dipyrrinone analogs, it can be translated to produce a wide range of conjugated bicyclic aromatic compounds. The Claisen-Schmidt condensation reaction utilized in this method is limited in scope to nucleophiles and electrophiles that are enolizable under basic conditions (nucleophile component) and non-enolizable aldehydes (electrophile component). Additionally, both the nucleophilic and electrophilic reactants must contain functional groups that will not inadvertently react with hydroxide. Despite these limitations, this methodology offers access to completely novel systems that can be employed as biological or molecular probes.

The Claisen-Schmidt condensation reaction is an important methodology for the generation of methine-bridged conjugated bicyclic aromatic compounds. Through utilizing a base-mediated variant of the aldol reaction, a range of fluorescent and/or biologically relevant molecules can be accessed through a generally inexpensive and operationally simple synthetic approach.

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