我々は、この作業を支援するためにニューヨーク州立大学ストーニーブルック校からの寛大なスタートアップ資金を認めます。また、Togni試薬IIの合成のために私たちにTMSCF 3試薬を提供するための東ソーエフテック社に感謝します。

1.前駆体調製：メチル4-（N個の -hydroxyacetamido）安息香酸（1A）の合成<ol><li> メチル-4-ニトロベンゾエートの削減。 <ol><li>オーブン乾燥した250ミリリットル二にメチル-4-ニトロベンゾエート（27.6ミリモル、1.00当量）、炭素上の5％ロジウムの159 mgのロジウム（Rh / C、0.300モル％RH）、および磁気撹拌棒を5.00グラムを追加します。 （18時間150℃で乾燥した）首丸底フラスコ。 注：試薬は、周囲雰囲気下で秤量することができます。しかし、反応は窒素雰囲気下で行う必要があります。 </li><li>フラスコの1首は、窒素/真空マニホールドに接続し、セプタムで他の首をキャップ。窒素ガスでフラスコ内の空気を交換するために、3つの真空リフィルサイクル（ すなわち、フラスコから空気をポンピングし、窒素ガスで得られる真空を交換）を行います。 </li><li>気密シリンジを用いて反応フラスコに、138 mlの無水テトラヒドロフラン（THF、0.200 M）を加えます。クールで反応MIXTをかき混ぜます15分間0℃でURE。 </li><li>気密シリンジを用いて0℃で反応混合物にヒドラジン一水和物の1.47 mlの（1.52グラム、30.4ミリモル、1.20当量）を滴下して加えます。薄層クロマトグラフィー（TLC）を用いて反応をモニターします。ヘキサンを使用してください：酢酸エチル（EtOAc）で（4：1 V / V は 、R f = 0.23）を溶離液として、TLCを開発します。 </li><li>メチル4-ニトロ安息香酸が完全に消費されると、珪藻土の短いパッドを通して反応混合物をフィルタリングする（ すなわち、セライト、5g）を60 mlの中には、真空濾過を用いてブフナー漏斗をフリット。酢酸エチル（×3回20ml）でフィルターを洗ってください。さらに精製せずに直接使用され、粗4-（N -hydroxyamino）安息香酸を得たロータリーエバポレーターを用いて減圧下でろ液を濃縮します。 </li></ol></li><li> 4-（N個の -hydroxyamino）安息香酸のアセチル保護 <ol><li>炭酸水素ナトリウムの2.55グラム（のNaHCO 3、30.4ミリモル、1.20当量）を追加し、すべての粗前のステップから得られたメチル4-（N個の -hydroxyamino）安息香酸、およびオーブン乾燥し500ミリリットルの二口丸底フラスコに撹拌棒。 </li><li>隔壁を有するキャップ1首と窒素/真空マニホールドに別の首を接続します。窒素ガスでフラスコ内の空気を置換するために、3つの真空リフィルサイクルを実行します。 </li><li>気密シリンジを用いて反応フラスコに138 mlのを無水ジエチルエーテル（Et 2 O、0.200 M）を加えます。冷却し、15分間0℃で反応混合物を攪拌します。 </li><li>無水のEt 2 O（138ミリリットル、0.220 M）に塩化アセチルの溶液（2.17ミリリットル、2.39グラム、30.4ミリモル、1.20当量）を準備します。 10.0ミリリットル/時の速度でシリンジポンプを用いて0℃で反応混合物の溶液を加えます。 </li><li>添加の終わりには、珪藻土の短いパッドを通して反応混合物をフィルタリングする（ すなわち、セライト、5g）を60 mlの中には、真空濾過を用いてブフナー漏斗をフリット。酢酸エチル（×3回20ml）でフィルターを洗ってください。集中ロータリーエバポレーターを用いて減圧下でろ液。 </li><li>ヘキサンで溶出するフラッシュカラムクロマトグラフィー35と、粗生成物を精製：酢酸エチル（4：1〜1：1（V / V））（ 式中、R f = 0.13、ヘキサン：EtOAc（4：1（v / v）で）5.31を得明黄色の固体（25.4ミリモル、92％収率）として4-（Nの -hydroxyacetamido）安息香酸のグラム。 </li></ol></li></ol>安息香酸（2A） -メチル4-（（トリフルオロメトキシ）アセトアミド、N）の2合成<ol><li> 、4-（Nの -hydroxyacetamido）安息香酸（1A）（9.56ミリモル、1.00当量）、2.00gの、 の Cs 2 CO 3の311ミリグラム（0.956ミリモル、10.0モル％）、Togni試薬IIの3.63グラム（11.5ミリモルを加えます1.20当量）、及びグローブボックス（窒素雰囲気）内部のオーブン乾燥した250mLの丸底フラスコに磁気攪拌棒。 注：この反応はまた、グローブボックスの外にシュレンク法を用いて行うことができます。 注意：ピュアTogni試薬IIは、衝撃や摩擦に敏感な、オープン炎でありますSは、火花、および/または粉砕は回避されるべきです。ソフトで洗練されたツールは、操作のために使用されるべきです。加えて、反応混合物は、安全シールドの背後に攪拌されるべきである。36 </li><li>乾燥の95.6ミリリットルを添加し、反応フラスコに、クロロホルム（CHCl 3を、0.100 M）を脱気しました。 </li><li>隔壁を有するフラスコに蓋をし ​​、内部または16時間グローブボックスの外側のいずれかにN 2雰囲気下、23℃で反応混合物を撹拌しました。 </li><li>任意の固体残留物を除去するためのフィルタ漏斗を通して反応混合物をろ過します。ロータリーエバポレーターを用いて減圧下でろ液を濃縮します。 </li><li>ヘキサンで溶出するフラッシュカラムクロマトグラフィーで粗生成物を精製：ジクロロメタン（CH 2 Cl 2）（7：3~0：1（V / V））（ 式中、R f = 0.44（CH 2 Cl 2）を得ました メチル4- 2.51グラム（N - （トリフルオロメトキシ）アセトアミド）安息香酸（9.05ミリモル、95％収率）。 注：Togni試薬IIは、準備された協定であります文献の手順37にると、長期間にわたって、その品質を維持するために、-35℃のグローブボックスの冷凍庫に保存されています。この反応は、酸素に敏感です。全ての試薬を室温で大気雰囲気下で秤量することができるが、反応フラスコから全ての酸素を除去することは重要です。乾燥および凍結-ポンプ-解凍手順の3つのサイクルを行うことによって、その後、窒素雰囲気下にCaH 2から蒸留することにより調製されるのCHCl 3脱気。 </li></ol> OCF 3 -migration（3A） を介して、メチル4-アセトアミド-3-（トリフルオロメトキシ）安息香酸の合成3。 <ol><li> 50ミリリットル圧力容器に安息香酸（9.05ミリモル、1.0当量）、磁気撹拌棒、及びメノ2（1.00 M）の9.05ミリリットル- 2.51グラムのメチル4-（（トリフルオロメトキシ）アセトアミド、N）を追加します 。スクリューキャップ付き容器に蓋を。 </li><li> 20時間、安全シールドの背後に120℃で反応混合物を撹拌しました。 注意：不純ニトロメタン爆発的であるため、反応混合物は、安全シールドの背後に攪拌する必要があります。 </li><li> RTに反応混合物を冷却します。 </li><li> 100 mlの丸底フラスコに、反応混合物を移します。 </li><li>ロータリーエバポレーターを用いて減圧下で反応混合物を濃縮します。 </li><li>ヘキサンで溶出するフラッシュカラムクロマトグラフィーで粗生成物を精製：酢酸エチル（9：1〜7：3（v / v）で）（ 式中、R f = 0.51、ヘキサン：酢酸エチル（4：1（V / V））を得ました メチル4-アセトアミド-3-（トリフルオロメトキシ）安息香酸の2.13グラム（7.69ミリモル、85％）。 注：この反応は、周囲雰囲気下で行うことができます。窒素雰囲気を必要としません。水冷却器を備えた丸底フラスコに、代替の反応装置として使用することができます。 </li></ol>新製品の4キャラクタリゼーション<ol><li> 1 H、13 C NMR分光法及び高分解能質量分析により、すべての新規化合物を特徴付け、19 F NMR分光法を使用しフッ素原子を有する化合物を特徴づける。34 </li></ol>

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Rev. 96, 1717-1736 (1996).</li><li>Venturini, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct+trifluoro-methoxylation+of+aromatics+with+perfluoro-methyl-hypofluorite.">Direct trifluoro-methoxylation of aromatics with perfluoro-methyl-hypofluorite.</a> J. Fluorine Chem. 140, 43-48 (2012).</li><li>Hojczyk, K. N., Feng, P., Zhan, C., Ngai, M. -. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Trifluoromethoxylation+of+arenes:+synthesis+of+ortho-trifluoromethoxylated+aniline+derivatives+by+OCF3+migration.">Trifluoromethoxylation of arenes: synthesis of ortho-trifluoromethoxylated aniline derivatives by OCF3 migration.</a> Angew. Chem. Int. Ed. 53, 14559-14563 (2014).</li><li>Still, W. 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.

原因trifluoromethoxylatedアレーンの合成のための一般的かつユーザーフレンドリーな手続きの欠如、多くのOCFに3含有芳香族化合物は、非常に高価である。34我々の戦略は、広範な官能基の許容値を置換し、様々なtrifluoromethoxylatedアレーンへの容易なアクセスを提供します。これらの化合物は、新たな医薬品、農薬、および材料の発見と開発にするための貴重なビルディング・ブロ...

トリフルオロメトキシ（OCF 3）グループは、高い電気陰性のそのユニークな組み合わせ（χ= 3.7）3と優れた親油性（ΠX =に1935年2におけるトリフルオロメチルエーテルの最初の合成以来、生命や材料科学の研究に大きな影響を与えてきました1.04）、4トリフルオロメトキシ基が医学、農業、素材産業において幅広い用途が見出されている。有機分子へのOCF 3グループの5〜10ただし、容易な導入、特に芳香族化合物は、合成化学における大きな課題です。 過去数十年にわたり、この課題に対処するための努力はtrifluoromethoxylatedアレーンの合成のための変換の一握りの開発につながっ5-7,9-11トリクロロ化前駆体のこれらは、（i）塩素/フッ素交換; 1,12フルオロホルメートの-17（ⅱ）deoxyfluorination; 18 </SUP&gt;（III）の酸化fluorodesulfurization; 19-21（IV）アルコールの求電子トリフルオロメチル; 22〜25（v）の求核trifluoromethoxylation; 26-30、アリールホウ酸塩およびスタンナンの（VI）遷移金属媒介trifluoromethoxylation; 31とを（VII ）ラジカルtrifluoromethoxylation。32,33しかしながら、これらの手法の多くは貧しい基板範囲に苦しむまたは非常に毒性および/ ​​または熱的に不安定な試薬の使用を必要とするのいずれか。そのため、OCF 3含有化合物を合成するための一般的かつユーザーフレンドリーな方法がないために、OCF 3グループの可能性は完全に化学で利用されていません。 trifluoromethoxylation反応における我々の関心の一環として、34我々は 、メチル4-アセトアミド-3-（トリフルオロメトキシの合成のために本明細書中に二段階プロトコル（ すなわち、Oラジカルの -trifluoromethylationと熱誘起OCF 3 -migration）を記述4-（N個の -hydroxyacetamido）安息香酸（1Aから）安息香酸（3A））。戦略がto-動作-やすく、 オルト -trifluoromethoxylatedアニリン誘導体の広い範囲の合成にも適用可能です。

<table border="0" cellpadding="0" cellspacing="0" width="573">
	<tbody>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">5% Rhodium on carbon</td>
			<td style="width:71px;">Aspira Scientific</td>
			<td style="width:119px;">300835</td>
			<td style="width:167px;">5% wt% dry loading</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">hydrazine monohydrate</td>
			<td style="width:71px;">Sigma-Alderich</td>
			<td style="width:119px;">13696HMV</td>
			<td style="width:167px;">Reagent grade, 98%</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Acetyl chloride</td>
			<td style="width:71px;">Alfa Aesar</td>
			<td style="width:119px;">10176887</td>
			<td style="width:167px;">98%</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Sodium bicarbonate</td>
			<td style="width:71px;">Fisher Scientific</td>
			<td style="width:119px;">134826</td>
			<td style="width:167px;">Chemical pure</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Cesium carbonate</td>
			<td style="width:71px;">Alfa Aesar</td>
			<td style="width:119px;">12887</td>
			<td style="width:167px;">99.9%, metals basis</td>
		</tr>
		<tr height="148">
			<td height="148" style="height:148px;width:216px;">Togni Reagent II</td>
			<td style="width:71px;"></td>
			<td style="width:119px;"></td>
			<td style="width:167px;">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 height="64">
			<td height="64" style="height:64px;width:216px;">Tetrahydrofuran</td>
			<td style="width:71px;">BDH</td>
			<td style="width:119px;">BDH1149-4LG</td>
			<td style="width:167px;">Distilled from deep purple sodium benzophenone ketyl.</td>
		</tr>
		<tr height="64">
			<td height="64" style="height:64px;width:216px;">Diethyl Ether</td>
			<td style="width:71px;">Fisher Scientific</td>
			<td style="width:119px;">148221</td>
			<td style="width:167px;">Distilled from deep purple sodium benzophenone ketyl.</td>
		</tr>
		<tr height="47">
			<td height="47" style="height:47px;width:216px;">Chloroform</td>
			<td style="width:71px;">Fisher Scientific</td>
			<td style="width:119px;">141739</td>
			<td style="width:167px;">Dried over CaH2 and distilled</td>
		</tr>
		<tr height="47">
			<td height="47" style="height:47px;width:216px;">nitro methane</td>
			<td style="width:71px;">Alfa Aesar</td>
			<td style="width:119px;">J03z053</td>
			<td style="width:167px;">Dried over CaSO4 and distilled</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:216px;">Silica gel</td>
			<td style="width:71px;">SILICYCLE</td>
			<td style="width:119px;">60514</td>
			<td style="width:167px;">40-63 &#181;m (230-400 mesh)</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:216px;">Cilite</td>
			<td style="width:71px;">EMD</td>
			<td style="width:119px;">2012040674</td>
			<td style="width:167px;">Not acid washed</td>
		</tr>
	</tbody>
</table>

protocol for the synthesis of ortho-trifluoromethoxylated aniline derivatives

トリフルオロメトキシ（OCF 3）基を有する分子は、多くの場合、所望の薬理学的および生物学的特性を示します。しかし、trifluoromethoxylated芳香族化合物の容易な合成は、有機合成における手ごわい課題です。従来のアプローチは、しばしば悪い基質範囲に苦しむ、または毒性の高い、難ハンドルの使用を必要とし、および/または熱的に不安定な試薬。ここで、我々が使用してメチル4-アセトアミド-3-（トリフルオロメトキシ）安息香酸の合成のためのユーザーフレンドリーなプロトコルを報告1トリフルオロメチル-1,2- benziodoxol-3（1H） -オン（Togni試薬II）。 （ - （トリフルオロメトキシ）アセトアミドN）安息香酸を室温でクロロホルム中で炭酸セシウム（Cs 2 CO 3）の触媒量の存在下でTogni試薬IIと4-（Nの -hydroxyacetamido）安息香酸（1a）を処理して、メチル4-得（ 図2a）。この中間体は、最終生成物メチル4-アセトアミド-3-（トリフルオロに変換しました。120℃でのニトロメタン中thoxy）安息香酸（3A）。この手順は一般的であり、新たな医薬品、農薬および機能性材料の発見及び開発のためのような有用な合成ビルディングブロックとして役立つ可能性がオルト -trifluoromethoxylatedアニリン誘導体、広範囲の合成に適用することができます。

4-（Nの -hydroxyacetamido）安息香酸（1a）は 、即ち、触媒として5％のRh / Cを使用して、ヒドラジンとメチル4-ニトロベンゾエートを減らすことメチル4-（形成する（2ステップの手順を介して92％の単離収率で合成しました。 RTでクロロホルム中炭酸セシウム（Cs 2 CO 3の触媒量の存在下でTogni試薬IIを有する得られたヒドロキシルア...

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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives

の合成のためのプロトコル<em&gt;オルソ</em&gt; -trifluoromethoxylatedアニリン誘導体

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

Aromatic Compounds

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9.8K ビュー.  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.

ビデオ: 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.

生成Cyanocarbenesの適用のための超原子価ヨードニウムアルキニルトリフラートの合成

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

化学

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.

中間過酸化物を介した光化学および酸触媒CH機能化による抗ウイルステトラヒドロカルバゾール誘導体の合成（チップ）

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 ...

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important structural element found in many complex natural products and pharmaceuticals. Owing to the continual discovery of new guanidine-containing natural products and designed small molecules, rapid and efficient guanidinylation methods are of keen interest to synthetic and medicinal organic chemists. Because the nucleophilicity and basicity of guanidines can affect subsequent chemical transformations, traditional, indirect guanidinylation is typically pursued. Indirect methods commonly employ multiple protection steps involving a latent amine precursor, such as an azide, phthalimide, or carbamate. By circumventing these circuitous methods and employing a direct guanidinylation reaction early in the synthetic sequence, it was possible to forge the linear terminal guanidine containing backbone of clavatadine A to realize a short and streamlined synthesis of this potent factor XIa inhibitor. In practice, guanidine hydrochloride is elaborated with a carefully constructed protecting array that is optimized to survive the synthetic steps to come. In the preparation of clavatadine A, direct guanidinylation of a commercially available diamine eliminated two unnecessary steps from its synthesis. Coupled with the wide variety of known guanidine protecting groups, direct guanidinylation evinces a succinct and efficient practicality inherent to methods that find a home in a synthetic chemist&#39;s toolbox.

Here, we present a protocol for direct, early stage guanidinylation that enables rapid total synthesis of aminoguanidine-containing small organic molecules. An advanced synthetic intermediate used in the synthesis of a blood coagulation factor XIa inhibitor was prepared using this protocol.

複雑なアミノグアニジン含有天然物の合成のための直接、早期グアニジニルプロトコル

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important ...

HKUST-1 as a Heterogeneous Catalyst for the Synthesis of Vanillin

Vanillin (4-hydoxy-3-methoxybenzaldehyde) is the main component of the extract of vanilla bean. The natural vanilla scent is a mixture of approximately 200 different odorant compounds in addition to vanillin. The natural extraction of vanillin (from the orchid Vanilla planifolia, Vanilla tahitiensis and Vanilla pompon) represents only 1% of the worldwide production and since this process is expensive and very long, the rest of the production of vanillin is synthesized. Many biotechnological approaches can be used for the synthesis of vanillin from lignin, phenolic stilbenes, isoeugenol, eugenol, guaicol, etc., with the disadvantage of harming the environment since these processes use strong oxidizing agents and toxic solvents. Thus, eco-friendly alternatives on the production of vanillin are very desirable and thus, under current investigation. Porous coordination polymers (PCPs) are a new class of highly crystalline materials that recently have been used for catalysis. HKUST-1 (Cu3(BTC)2(H2O)3, BTC = 1,3,5-benzene-tricarboxylate) is a very well known PCP which has been extensively studied as a heterogeneous catalyst. Here, we report a synthetic strategy for the production of vanillin by the oxidation of trans-ferulic acid using HKUST-1 as a catalyst.

The conversion of trans-ferulic acid to vanillin was achieved by heterogeneous catalysis. HKUST-1 was employed in this synthesis and the essential step in the catalytic process was the generation of unsaturated metal sites. Thus, when the catalyst was activated under vacuum, full vanillin conversion (yield of 95%) was obtained.

HKUST-1バニリンの合成のための不均一触媒として、

Vanillin (4-hydoxy-3-methoxybenzaldehyde) is the main component of the extract of vanilla bean. The natural vanilla scent is a mixture of approximately ...

A Protocol for the Production of Gliadin-cyanoacrylate Nanoparticles for Hydrophilic Coating

This article presents a protocol for the production of protein-based nanoparticles that changes the hydrophobic surface to hydrophilic by a simple spray coating. These nanoparticles are produced by the polymerization reaction of alkyl cyanoacrylate on the surface of cereal protein (gliadin) molecules. Alkyl cyanoacrylate is a monomer that instantly polymerizes at RT when it is applied to the surface of materials. Its polymerization reaction is initiated by the trace amounts of weakly basic or nucleophilic species on the surface, including moisture. Once polymerized, the polymerized alkyl cyanoacrylates show a strong affinity with the object materials because nitrile groups are in the backbone of poly (alkyl cyanoacrylate). Proteins also work as initiator for this polymerization because they contain amine groups that can initiate the polymerization of cyanoacrylate. If aggregated protein is used as an initiator, protein aggregate is surrounded by the hydrophobic poly(alkyl cyanoacrylate) chains after the polymerization reaction of alkyl cyanoacrylate. By controlling the experimental condition, particles in the nanometer range are produced. The produced nanoparticles readily adsorb to the surface of most materials including glass, metals, plastics, wood, leather, and fabrics. When the surface of a material is sprayed with the produced nanoparticle suspension and rinsed with water, the micellar structure of nanoparticle changes its conformation, and the hydrophilic proteins are exposed to the air. As a result, the nanoparticle-coated surface changes to hydrophilic.

This article presents a protocol for the production of protein-based nanoparticles that changes the hydrophobic surface to hydrophilic. The produced nanoparticle is an assembly of gliadin-cyanoacrylate diblock copolymers. Spray coating with the produced nanoparticle changes the surface of target material to a hydrophilic surface.

親水性コーティングのためのグリアジンシアノアクリレートナノ粒子の製造のためのプロトコル

This article presents a protocol for the production of protein-based nanoparticles that changes the hydrophobic surface to hydrophilic by a simple spray ...

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the development of antibody drug conjugates (ADCs) and nanomedicine, fluorescent microscopy and systems chemistry. For many of these applications, specificity of the bioconjugation method used is of prime concern. The Michael addition of maleimides with cysteine(s) on the target proteins is highly selective and proceeds rapidly under mild conditions, making it one of the most popular methods for protein bioconjugation.
We demonstrate here the modification of the only surface-accessible cysteine residue on yeast cytochrome c with a ruthenium(II) bisterpyridine maleimide. The protein bioconjugation is verified by gel electrophoresis and purified by aqueous-based fast protein liquid chromatography in 27% yield of isolated protein material. Structural characterization with MALDI-TOF MS and UV-Vis is then used to verify that the bioconjugation is successful. The protocol shown here is easily applicable to other cysteine - maleimide coupling of proteins to other proteins, dyes, drugs or polymers.

Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry

This protocol details the important steps required for the bioconjugation of a cysteine containing protein to a maleimide, including reagent purification, reaction conditions, bioconjugate purification and bioconjugate characterization.

タンパク質のバイオコンジュゲートの合成<em&gt;経由で</em&gt;システイン - マレイミドケミストリー

The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the ...

Facile Synthesis of Worm-like Micelles by Visible Light Mediated Dispersion Polymerization Using Photoredox Catalyst

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins with the synthesis of a hydrophilic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) homopolymer using reversible addition-fragmentation chain-transfer (RAFT) polymerization. Under mild visible light irradiation (&#955; = 460 nm, 0.7 mW/cm2), this macro-chain transfer agent (macro-CTA) in the presence of a ruthenium based photoredox catalyst, Ru(bpy)3Cl2 can be chain extended with a second monomer to form a well-defined block copolymer in a process known as Photoinduced Electron Transfer RAFT (PET-RAFT). When PET-RAFT is used to chain extend POEGMA with benzyl methacrylate (BzMA) in ethanol (EtOH), polymeric nanoparticles with different morphologies are formed in situ according to a polymerization-induced self-assembly (PISA) mechanism. Self-assembly into nanoparticles presenting POEGMA chains at the corona and poly(benzyl methacrylate) (PBzMA) chains in the core occurs in situ due to the growing insolubility of the PBzMA block in ethanol. Interestingly, the formation of highly pure worm-like micelles can be readily monitored by observing the onset of a highly viscous gel in situ due to nanoparticle entanglements occurring during the polymerization. This process thereby allows for a more reproducible synthesis of worm-like micelles simply by monitoring the solution viscosity during the course of the polymerization. In addition, the light stimulus can be intermittently applied in an ON/OFF manner demonstrating temporal control over the nanoparticle morphology.

This article describes a process for producing polymeric self-assembled nanoparticles using visible light mediated dispersion polymerization. Using low energy visible light to control the polymerization allows for the reproducible formation of self-assembled worm-like micelles at high solids content.

Photoredox触媒を用いた可視光媒介分散重合によるワームのようなミセルの簡便な合成

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins ...

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

Solid-phase synthesis has been used to obtain canonical and modified polymers of nucleic acids, specifically of DNA or RNA, which has made it a popular methodology for applications in various fields and for different research purposes. The procedure described herein focuses on the synthesis, purification, and characterization of dodecamers of RNA 5&#39;-[CUA CGG AAU CAU]-3&#39; containing zero, one, or two modifications located at the C2&#39;-O-position. The probes are based on 2-thiophenylmethyl groups, incorporated into RNA nucleotides via standard organic synthesis and introduced into the corresponding oligonucleotides via their respective phosphoramidites. This report makes use of phosphoramidite chemistry via the four canonical nucleobases (Uridine (U), Cytosine (C), Guanosine (G), Adenosine (A)), as well as 2-thiophenylmethyl functionalized nucleotides modified at the 2&#39;-O-position; however, the methodology is amenable for a large variety of modifications that have been developed over the years. The oligonucleotides were synthesized on a controlled-pore glass (CPG) support followed by cleavage from the resin and deprotection under standard conditions, i.e., a mixture of ammonia and methylamine (AMA) followed by hydrogen fluoride/triethylamine/N-methylpyrrolidinone. The corresponding oligonucleotides were purified via polyacrylamide electrophoresis (20% denaturing) followed by elution, desalting, and isolation via reversed-phase chromatography (Sep-pak, C18-column). Quantification and structural parameters were assessed via ultraviolet-visible (UV-vis) and circular dichroism (CD) photometric analysis, respectively. This report aims to serve as a resource and guide for beginner and expert researchers interested in embarking in this field. It is expected to serve as a work-in-progress as new technologies and methodologies are developed. The description of the methodologies and techniques within this document correspond to a DNA/RNA synthesizer (refurbished and purchased in 2013) that uses phosphoramidite chemistry.

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

This article provides a detailed procedure on the solid-phase synthesis, purification, and characterization of dodecamers of RNA modified at the C2&#39;-O-position. UV-vis and circular dichroism photometric analyses are used to quantify and characterize structural aspects, i.e., single-strands or double-strands.

2 &#39;末端を含むRNAのオリゴマーの固相合成のためのプロトコール<em&gt; O</em&gt;チオフェンメチル修飾と環状二色性によるキャラクタリゼーション

Solid-phase synthesis has been used to obtain canonical and modified polymers of nucleic acids, specifically of DNA or RNA, which has made it a popular ...

Synthesis and Mass Spectrometry Analysis of Oligo-peptoids

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have been thought of as a type of molecular information storage. Mass spectrometry analysis has been considered the method of choice for sequencing peptoids. Peptoids can be synthesized via solid phase chemistry using a repeating two-step reaction cycle. Here we present a method to manually synthesize oligo-peptoids and to analyze the sequence of the peptoids using tandem mass spectrometry (MS/MS) techniques. The sample peptoid is a nonamer consisting of alternating N-(2-methyloxyethyl)glycine (Nme) and N-(2-phenylethyl)glycine (Npe), as well as an N-(2-aminoethyl)glycine (Nae) at the N-terminus. The sequence formula of the peptoid is Ac-Nae-(Npe-Nme)4-NH2, where Ac is the acetyl group. The synthesis takes place in a commercially available solid-phase reaction vessel. The rink amide resin is used as the solid support to yield the peptoid with an amide group at the C-terminus. The resulting peptoid product is subjected to sequence analysis using a triple-quadrupole mass spectrometer coupled to an electrospray ionization source. The MS/MS measurement produces a spectrum of fragment ions resulting from the dissociation of charged peptoid. The fragment ions are sorted out based on the values of their mass-to-charge ratio (m/z). The m/z values of the fragment ions are compared against the nominal masses of theoretically predicted fragment ions, according to the scheme of peptoid fragmentation. The analysis generates a fragmentation pattern of the charged peptoid. The fragmentation pattern is correlated to the monomer sequence of the neutral peptoid. In this regard, MS analysis reads out the sequence information of the peptoids.

A protocol is described for the manual synthesis of oligo-peptoids followed by sequence analysis by mass spectrometry.

合成とオリゴ ペプチドの質量分析

Peptoids are sequence-controlled peptide-mimicking oligomers consisting of N-alkylated glycine units. Among many potential applications, peptoids have ...

The MPLEx Protocol for Multi-omic Analyses of Soil Samples

Mass spectrometry (MS)-based integrated metaproteomic, metabolomic, and lipidomic (multi-omic) studies are transforming our ability to understand and characterize microbial communities in environmental and biological systems. These measurements are even enabling enhanced analyses of complex soil microbial communities, which are the most complex microbial systems known to date. Multi-omic analyses, however, do have sample preparation challenges, since separate extractions are typically needed for each omic study, thereby greatly amplifying the preparation time and amount of sample required. To address this limitation, a 3-in-1 method for the simultaneous extraction of metabolites, proteins, and lipids (MPLEx) from the same soil sample was created by adapting a solvent-based approach. This MPLEx protocol has proven to be both simple and robust for many sample types, even when utilized for limited quantities of complex soil samples. The MPLEx method also greatly enabled the rapid multi-omic measurements needed to gain a better understanding of the members of each microbial community, while evaluating the changes taking place upon biological and environmental perturbations.

A protocol is presented for simultaneously extracting metabolites, proteins, and lipids from a single soil sample, allowing reduced sample preparation times and enabling multi-omic mass spectrometry analyses of samples with limited quantities.

マルチ弔土壌試料の分析のための MPLEx プロトコル

Mass spectrometry (MS)-based integrated metaproteomic, metabolomic, and lipidomic (multi-omic) studies are transforming our ability to understand and ...

の合成のためのプロトコル

要約

さらに動画を探す

この動画の章

生成Cyanocarbenesの適用のための超原子価ヨードニウムアルキニルトリフラートの合成

中間過酸化物を介した光化学および酸触媒CH機能化による抗ウイルステトラヒドロカルバゾール誘導体の合成（チップ）

複雑なアミノグアニジン含有天然物の合成のための直接、早期グアニジニルプロトコル

HKUST-1バニリンの合成のための不均一触媒として、

親水性コーティングのためのグリアジンシアノアクリレートナノ粒子の製造のためのプロトコル

タンパク質のバイオコンジュゲートの合成

Photoredox触媒を用いた可視光媒介分散重合によるワームのようなミセルの簡便な合成

2 '末端を含むRNAのオリゴマーの固相合成のためのプロトコール

合成とオリゴペプチドの質量分析

マルチ弔土壌試料の分析のための MPLEx プロトコル

の合成のためのプロトコル

要約

さらに動画を探す

この動画の章

生成Cyanocarbenesの適用のための超原子価ヨードニウムアルキニルトリフラートの合成

中間過酸化物を介した光化学および酸触媒CH機能化による抗ウイルステトラヒドロカルバゾール誘導体の合成（チップ）

複雑なアミノグアニジン含有天然物の合成のための直接、早期グアニジニルプロトコル

HKUST-1バニリンの合成のための不均一触媒として、

親水性コーティングのためのグリアジンシアノアクリレートナノ粒子の製造のためのプロトコル

タンパク質のバイオコンジュゲートの合成

Photoredox触媒を用いた可視光媒介分散重合によるワームのようなミセルの簡便な合成

2 '末端を含むRNAのオリゴマーの固相合成のためのプロトコール

合成とオリゴ ペプチドの質量分析

マルチ弔土壌試料の分析のための MPLEx プロトコル

合成とオリゴペプチドの質量分析