一项由爱丽大学提供的创业补助金和一份独立研究补助金 (1914/15) 给 AMS 的致谢。

1. Enolonium 种的制备
注意: 在执行该协议之前, 请查阅所有试剂和溶剂的 MSDS。
注: 所有新试剂均使用从商业来源收到。如果已经储存了三氟化硼乙醚, 在使用前先蒸馏。
<ol><li>在一个干燥的圆底烧瓶, 装有隔膜和磁铁搅拌, 添加科泽的试剂 (1.5 equiv), 并冲洗瓶与氮气或氩气。</li>
	<li>添加干二氯甲烷, 使悬浮0.234 摩尔/L 正式浓度。</li>
	<li>使用干冰/丙酮浴或冷指仪器/丙酮浴冷却悬浮到-78 °c。</li>
	<li>加整齐的 BF3氨基酸2 (1.5 equiv) 慢慢地。</li>
	<li>将异质混合物加热到室温, 直至形成黄溶液。通常情况下, 这发生在5分钟以内。</li>
	<li>冷却溶液到-78 摄氏度。</li>
	<li>对冷却溶液, 加入三甲基硅 enolether (1 equiv, 0.313 摩尔/升) 在干二氯甲烷滴状超过2-10 分钟 (取决于鳞片)。硅烯醇式醚的加入完成后, enolonium 种的形成是完整的。 注: enolonium 物种的溶液可在-78 摄氏度左右, 至少30分钟, 产量不变。enolonium 的物种在这段时间是稳定的, 如报告的核磁共振研究6所示。</li>
</ol>2. Enolonium 种的功能化
<ol><li>氯化阴离子
	<ol>
<li>对 enolonium 种的制备溶液, 在干二氯甲烷中加入苄基甲基 decylammonium 氯 (2.0 equiv, 1.25 摩尔/升), 以降明智的方式。按速率添加此解决方案, 使温度保持在摄氏-55 摄氏度以下。在 0.5-2 毫摩尔规模, 增加超过5分钟是令人满意的。</li>
		<li>将反应混合物保持在-78 摄氏度, 5 分钟。</li>
		<li>除去冷却液, 使反应混合物达到室温。</li>
		<li>将反应在室温下保持20分钟。</li>
		<li>将水添加到反应混合物中 (用于制备 enolonium 种的二氯甲烷体积的一半)。</li>
		<li>二氯甲烷三次萃取。通常, 使用2-3 倍的反应量在每次提取在 0.5-2 毫摩尔小规模。</li>
		<li>用盐水冲洗两次组合的有机层。通常, 使用相同的盐水量作为联合反应量。</li>
		<li>用无水硫酸钠干燥30分钟。</li>
		<li>过滤掉硫酸硫酸钠 (例如, 通过硅藻土插头)。</li>
		<li>在减压和40摄氏度的旋转蒸发器上去除溶剂。</li>
		<li>用己烷和醋酸乙酯 eluents 在硅胶上的柱层析法提纯原油, 在溶剂去除后, 叠氮基酮的纯对应。 注: 在0.5 毫摩尔到2毫摩尔的三甲基硅烯醇负离子的鳞片上, 在2厘米直径的玻璃柱上进行柱层析, 使用标准硅胶60在高度 (长度) 15 厘米。该卷将需要不同的规模。</li>
	</ol></li>
	<li>Azidation-叠氮化物 注意: 叠氮化合物一般都是爆炸性的, 应注意处理和准备产品。叠氮化物是有毒的。使用前请咨询 MSDS。<ol>
<li>在-78 摄氏度的 enolonium 物种的制备溶液中, 添加整齐的 azidotrimethylsilane (2.5 equiv) 以滴状的方式。以速率添加此解决方案, 以使温度保持在-55 摄氏度以下。在 0.5-2 毫摩尔规模, 增加超过2-3 分钟是令人满意的。</li>
		<li>搅拌反应混合物15分钟, 在-78 摄氏度。</li>
		<li>加热反应混合物到-55 °c 并且离开在这个温度为2到 3 h。</li>
		<li>将水添加到反应混合物中 (用于制备 enolonium 种的二氯甲烷体积的一半)。</li>
		<li>二氯甲烷三次萃取。通常, 使用2-3 倍的反应量在每次提取在 0.5-2 毫摩尔小规模。</li>
		<li>用盐水冲洗两次组合的有机层。通常, 使用相同的盐水量作为联合反应量。</li>
		<li>用无水硫酸钠干燥萃取物30分钟。</li>
		<li>过滤掉硫酸钠。</li>
		<li>在减压和40摄氏度的旋转蒸发器上去除溶剂。</li>
		<li>用己烷和醋酸乙酯 eluents 在硅胶上的柱层析法提纯原油, 在溶剂去除后, 叠氮基酮的纯对应。</li>
	</ol></li>
	<li>反应与唑类药物
	<ol>
<li>在-78 摄氏度的 enolonium 物种的制备溶液中, 加入唑 (4 至 5 equiv, 1 摩尔/升), 以滴状方式溶解在5毫升的二氯甲烷中。在 0.5-2 毫摩尔规模, 增加超过5分钟是令人满意的。 注: 在不溶性唑类药物如 tetrazoles 的情况下, 使用乙腈浓度为0.5 摩尔/升而不是二氯甲烷。以速率添加此解决方案, 以使温度保持在-55 摄氏度以下。</li>
		<li>搅拌反应混合物15分钟, 在-78 摄氏度。</li>
		<li>加热反应混合物到-55 °c 并且离开在这个温度为4到 8 h。</li>
		<li>将水添加到反应混合物中 (用于制备 enolonium 种的有机溶剂的一半)。</li>
		<li>二氯甲烷三次萃取。通常, 使用2-3 倍的反应量在每次提取在 0.5-2 毫摩尔小规模。</li>
		<li>用盐水冲洗两次组合的有机层。通常, 使用相同的盐水量作为联合反应量。</li>
		<li>用无水硫酸钠干燥萃取物30分钟。</li>
		<li>过滤掉硫酸钠。</li>
		<li>在减压和40摄氏度的旋转蒸发器上去除溶剂。</li>
		<li>用己烷和醋酸乙酯 eluents 在硅胶上的柱层析法提纯原油, 在溶剂去除后, 唑酮的纯对应。</li>
	</ol></li>
	<li>烯丙基、crotylation、cinnamylation 和 prenylation 使用烯丙基烷
	<ol>
<li>添加整齐的烯丙基,-, crotyl, 肉桂, 或梨醇 trimethylsilane (2 equiv) 缓慢在-78 摄氏度。以速率添加此解决方案, 以使温度保持在-55 摄氏度以下。在 0.5-2 毫摩尔规模, 增加超过2-3 分钟是令人满意的。</li>
		<li>搅拌反应混合物10分钟, 在-78 摄氏度。</li>
		<li>通过去除冷却浴, 让反应混合物慢慢地温暖到室温。将反应在室温下保持20分钟。</li>
		<li>将水添加到反应混合物中 (用于制备 enolonium 种的二氯甲烷体积的一半)。</li>
		<li>二氯甲烷三次萃取。通常, 使用2-3 倍的反应量在每次提取在 0.5-2 毫摩尔小规模。</li>
		<li>用盐水冲洗两次组合的有机层。通常, 使用相同的盐水量作为联合反应量。</li>
		<li>用无水硫酸钠干燥萃取物30分钟。</li>
		<li>过滤掉硫酸钠。</li>
		<li>在减压和40摄氏度的旋转蒸发器上去除溶剂。</li>
		<li>用己烷和醋酸乙酯 eluents 在硅胶上的柱层析法提纯粗品, 在溶剂去除后, 得到纯对应的α烯丙基产物。</li>
	</ol></li>
	<li>Arylation 注: 对于 arylation, 在 enolonium 物种的制备过程中, 使用3当量的 BF3氨基酸2 , 以避免 enolonium 物种 tosylation 为主要的副反应。一般而言, 只有1.6 当量的芳香基板是需要的。然而, 如果芳香基板是 pyrane, 噻吩, 或吡咯, 最好的结果是通过5当量的芳香基体。<ol>
<li>对制备的 enolonium 物种的解决方案, 在干二氯甲烷 (1.6 equiv, 0.5 摩尔/升) 中添加芳香基的溶液, 以滴状方式。以速率添加此解决方案, 以使温度保持在-55 摄氏度以下。在 0.5-2 毫摩尔规模, 增加超过5-10 分钟是令人满意的。</li>
		<li>在芳香基体的加法完成之后, 增加混合物的温度到-55 °c 并且离开混合物在这个温度为20分钟。</li>
		<li>将水添加到反应混合物中 (用于制备 enolonium 种的二氯甲烷体积的一半)。</li>
		<li>二氯甲烷三次萃取。通常, 使用2-3 倍的反应量在每次提取在 0.5-2 毫摩尔小规模。</li>
		<li>用盐水冲洗两次组合的有机层。通常, 使用相同的盐水量作为联合反应量。</li>
		<li>用无水硫酸钠干燥萃取物30分钟。</li>
		<li>过滤掉硫酸钠。</li>
		<li>在减压和40摄氏度的旋转蒸发器上去除溶剂。</li>
		<li>用己烷和醋酸乙酯 eluents 在硅胶上的柱层析法提纯原油, 在溶剂去除后, arylated 酮的纯对应。</li>
	</ol></li>
</ol>

<ol>
	<li>Mizar, P., Wirth, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Flexible+stereoselective+functionalizations+of+ketones+through+umpolung+with+hypervalent+iodine+reagents.">Flexible stereoselective functionalizations of ketones through umpolung with hypervalent iodine reagents.</a> Angewandte Chemie International Edition. 53 (23), 5993-5997 (2014).</li><li>Yoshimura, A., Zhdankin, V. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Advances+in+synthetic+applications+of+hypervalent+iodine+compounds.">Advances in synthetic applications of hypervalent iodine compounds.</a> Chemical Reviews. 116 (5), 3328-3435 (2016).</li><li>Zhdankin, V. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Hypervalent Iodine Chemistry: Preparation, Structure, and Synthetic Applications of Polyvalent Iodine Compounds. , (2013).</li><li>Wirth, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Topics in Current Chemistry. 373, (2016).</li><li>Merritt, E. A., Olofsson, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=&#945;-functionalization+of+carbonyl+compounds+using+hypervalent+iodine+reagents.">&#945;-functionalization of carbonyl compounds using hypervalent iodine reagents.</a> Synthesis. 4 (4), 517-538 (2011).</li><li>Arava, S., 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=Enolonium+Species-Umpoled+Enolates.">Enolonium Species-Umpoled Enolates.</a> Angewandte Chemie International Edition. 56 (10), 2599-2603 (2017).</li><li>Parida, K. N., Maksymenko, S., Pathe, G. K., Szpilman, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cross-Coupling+of+Dissimilar+Ketone+Enolates+via+Enolonium+Species+to+afford+Nonsymmetrical+1,4-Diketones.">Cross-Coupling of Dissimilar Ketone Enolates via Enolonium Species to afford Nonsymmetrical 1,4-Diketones.</a> Beilstein Journal of Organic Chemistry. 14, 992-997 (2018).</li><li>Zhdankin, V. V., 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=Carbon-carbon+bond+formation+in+reactions+of+PhIO&#183;HBF4-silyl+enol+ether+adduct+with+alkenes+or+silyl+enol+ethers.">Carbon-carbon bond formation in reactions of PhIO&#183;HBF4-silyl enol ether adduct with alkenes or silyl enol ethers.</a> Journal of Organic Chemistry. 54 (11), 2605-2608 (1989).</li><li>Maksymenko, S., 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=Transition-metal-free+intermolecular+&#945;-arylation+of+ketones+via+enolonium+species.">Transition-metal-free intermolecular &#945;-arylation of ketones via enolonium species.</a> Organic Letters. 19 (23), 6312-6315 (2017).</li><li>Vita, M. V., Waser, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Azidation+of+&#946;-keto+esters+and+silyl+enol+ethers+with+a+benziodoxole+reagent.">Azidation of &#946;-keto esters and silyl enol ethers with a benziodoxole reagent.</a> Organic Letters. 15 (13), 3246-3249 (2013).</li><li>More, A., 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=&#945;-N-Heteroarylation+and+&#945;-azidation+of+ketones+via+enolonium+species.">&#945;-N-Heteroarylation and &#945;-azidation of ketones via enolonium species.</a> Journal of Organic Chemistry. 83, 2442-2447 (2018).</li><li>Xie, L., 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=Gold-catalyzed+hydration+of+haloalkynes+to+&#945;-halomethyl+ketones.">Gold-catalyzed hydration of haloalkynes to &#945;-halomethyl ketones.</a> Journal of Organic Chemistry. 78 (18), 9190-9195 (2013).</li><li>Patonay, T., Juh&#225;sz-T&#243;th, &. #. 2. 0. 1. ;., B&#233;nyei, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Base-induced+coupling+of+&#945;-azido+ketones+with+aldehydes+&#8722;+An+easy+and+efficient+route+to+trifunctionalized+synthons+2-azido-3-hydroxy+ketones,+2-acylaziridines,+and+2-acylspiroaziridines.">Base-induced coupling of &#945;-azido ketones with aldehydes &#8722; An easy and efficient route to trifunctionalized synthons 2-azido-3-hydroxy ketones, 2-acylaziridines, and 2-acylspiroaziridines.</a> European Journal of Organic Chemistry. 2002 (2), 285-295 (2002).</li><li>Li, C., Breit, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rhodium-catalyzed+chemo-+and+regioselective+decarboxylative+addition+of+&#946;-ketoacids+to+allenes:+Efficient+construction+of+tertiary+and+quaternary+carbon+Centers.">Rhodium-catalyzed chemo- and regioselective decarboxylative addition of &#946;-ketoacids to allenes: Efficient construction of tertiary and quaternary carbon Centers.</a> Journal of the American Chemical Society. 136 (3), 862-865 (2014).</li></ol>

我们没有什么可透露的。

从 TMS-enolates 成功地制备 enolonium 物种取决于许多因素。在制备步骤中的主要副反应是由形成的 enolonium 分子与烯醇负离子分子的反应产生的起始材料的人偶联。因此, 反应条件的要求是避免这种二聚化通过确保快速反应的刘易斯酸活化高价碘试剂与增加 TMS 烯醇负离子相对于二聚化率。这是在协议中通过活化和溶解科泽试剂使用化学计量 BF3。许多高价碘试剂包括科泽试剂在标准有机溶剂中...

Enolates 是经典的碳亲核试剂在有机化学和其中最广泛使用。极性转换 enolates 创造亲 enolonium 物种允许有价值的替代方法, 以产生α功能性酮, 并使新的反应不可能通过经典的烯醇负离子化学。Enolonium 种在许多反应中被建议为中间体, 特别是涉及高价碘试剂的反应。这些反应包括α卤化, 氧合和胺化1以及其他反应2,3,4,5。
然而, 这些反应的范围总是受到反应 enolonium 物种瞬态性质的限制。这顷刻要求在反应混合物中存在任何亲核试剂在羰基 enolates 反应期间与强氧化高价碘试剂。因此, 任何亲核试剂易氧化, 如电子丰富的芳香化合物 (杂环化合物) 和烯烃, 不能使用。
在过去的一年里, 我们通过发展条件来克服这些限制, enolonium 物种在一个步骤中形成一个离散的中间, 然后在第二步加入亲核试剂。该协议不仅允许经典类型的功能化, 如氯化6, 而且使用氧化碳亲核试剂, 如 allylsilanes6,8, enolates1,6, 7、和电子丰富的芳香化合物9, 导致碳-碳键形成。烯丙基方法适合于第四纪和第三纪中心的形成。酮 arylation 法构成芳香化合物的正式 C H 功能化, 不需要指导组9。最近, 我们报告增加了唑类药物和叠氮化合物10以及11。该议定书的详细表述可望有助于将这些方法引入合成有机化学家的日常工具箱中。

<table>
	<tbody>
		<tr>
			<td>Chlorotrimethylsilane, 98+%</td>
			<td>Alfa Aesar</td>
			<td>A13651</td>
			<td>TMS-Cl</td>
		</tr>
		<tr>
			<td>Boron trifluoride diethyl etherate, 98+%</td>
			<td>Alfa Aesar</td>
			<td>A15275</td>
			<td>BF3*Et2O</td>
		</tr>
		<tr>
			<td>2-Methylindole, 98+%</td>
			<td>Alfa Aesar</td>
			<td>A10764</td>
			<td>2-Me-indole</td>
		</tr>
		<tr>
			<td>Hydroxy(tosyloxy) iodobenzene, 97%</td>
			<td>Alfa Aesar</td>
			<td>L15701</td>
			<td>Koser&#39;s reagent</td>
		</tr>
		<tr>
			<td>Acetophenone, &#62;98%</td>
			<td>Merck</td>
			<td>800028</td>
			<td></td>
		</tr>
		<tr>
			<td>n-Butyllithium solution 1.6M in hexanes</td>
			<td>Aldrich</td>
			<td>186171</td>
			<td>nBuLi</td>
		</tr>
		<tr>
			<td>BIS(ISOPROPYL)AMINE</td>
			<td>Apollo</td>
			<td>OR1090</td>
			<td>DIPA</td>
		</tr>
		<tr>
			<td>Trimethylsilyl azide, 94%</td>
			<td>Alfa Aesar</td>
			<td>L00173</td>
			<td>TMS-N3</td>
		</tr>
	</tbody>
</table>

a two-step protocol for umpolung functionalization of ketones via enolonium species

高价碘试剂 enolates 极性转换酮的α功能化是合成有机化学的一个重要概念。最近, 我们已经制定了两个步骤的战略, 酮烯醇负离子极性转换, 这使得发展的方法, 氯化, azidation 和胺化使用唑类药物。此外, 我们还开发了 c-bond–forming arylation 和烯丙基反应。这些方法的核心是在添加反应性亲核试剂之前制备中间和高活性 enolonium 种。这一策略使人联想到在古典合成化学中金属 enolates 的制备和使用。这种策略允许使用亲核试剂, 否则将与强烈氧化高价碘试剂不相容。本文提出了氯化、azidation、n-heteroarylation、arylation 和烯丙基的详细协议。产品包括在药用活性产品中流行的图案。本文将极大地帮助其他人使用这些方法。

图 1给出了根据该议定书取得的代表性成果, 并在讨论部分进行了讨论。值得注意的是, 很大范围的不同的酮可以成功地用于反应, 使产品的良好的产量, 可以看到的 azidation11。在酮α位置引入唑类药物反应的范围包括大多数常见的单循环和笼含杂环化合物氮。烯丙基过程的范围包括烯丙基、crotyl 和梨醇-trimethylsilane6?...

Watch this Scientific Journal Video about A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species at JoVE.com

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

本文介绍了极性转换酮 enolates 到 enolonium 种的两步单锅协议, 并对α位亲核试剂的添加进行了描述。亲核试剂包括氯、叠氮化物、唑类药物、烯丙基烷和芳香化合物。

Enolonium 种极性转换酮功能化的两步协议

&#945;-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. ...

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Organic Chemistry

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Unit 1

Aldehydes and Ketones

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9.9K 次观看.  Ariel University. 本文介绍了极性转换酮 enolates 到 enolonium 种的两步单锅协议, 并对α位亲核试剂的添加进行了描述。亲核试剂包括氯、叠氮化物、唑类药物、烯丙基烷和芳香化合物。

视频: A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species

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.

通过中级过氧化物的抗病毒四氢咔唑衍生物的合成光化学和酸催化CH官能（筹）

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 ...

科研

化学

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.

一种醇溶蛋白氰基丙烯酸酯纳米粒子为亲水涂料生产协议

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

Rapid High-throughput Species Identification of Botanical Material Using Direct Analysis in Real Time High Resolution Mass Spectrometry

We demonstrate that direct analysis in real time-high resolution mass spectrometry can be used to produce mass spectral profiles of botanical material, and that these chemical fingerprints can be used for plant species identification. The mass spectral data can be acquired rapidly and in a high throughput manner without the need for sample extraction, derivatization or pH adjustment steps. The use of this technique bypasses challenges presented by more conventional techniques including lengthy chromatography analysis times and resource intensive methods. The high throughput capabilities of the direct analysis in real time-high resolution mass spectrometry protocol, coupled with multivariate statistical analysis processing of the data, provide not only class characterization of plants, but also yield species and varietal information. Here, the technique is demonstrated with two psychoactive plant products, Mitragyna speciosa (Kratom) and Datura (Jimsonweed), which were subjected to direct analysis in real time-high resolution mass spectrometry followed by statistical analysis processing of the mass spectral data. The application of these tools in tandem enabled the plant materials to be rapidly identified at the level of variety and species.

A method for species identification of botanical material by direct analysis in real time-high resolution mass spectrometry and multivariate statistical analysis is presented.

植物材料的快速高通量物种鉴定实时高分辨质谱法直接分析

We demonstrate that direct analysis in real time-high resolution mass spectrometry can be used to produce mass spectral profiles of botanical material, ...

A Protocol for Safe Lithiation Reactions Using Organolithium Reagents

Organolithium reagents are powerful tools in the synthetic chemist&#39;s toolbox. However, the extreme pyrophoric nature of the most reactive reagents warrants proper technique, thorough training, and proper personal protective equipment. To aid in the training of researchers using organolithium reagents, a thorough, step-by-step protocol for the safe and effective use of tert-butyllithium on an inert gas line or within a glovebox is described. As a model reaction, preparation of lithium tert-butyl amide by the reaction of tert-butyl amine with one equivalent of tert-butyl lithium is presented.

The safe and proper use of organolithium reagents is described.

使用有机锂试剂的一个协议安全的锂化反应

Organolithium reagents are powerful tools in the synthetic chemist&#39;s toolbox. However, the extreme pyrophoric nature of the most reactive reagents ...

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.

用于固相合成含有2&#39;-<em&gt; 0</em通过圆二色性修饰和表征

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 ...

Fabrication and Testing of Catalytic Aerogels Prepared Via Rapid Supercritical Extraction

Protocols for preparing and testing catalytic aerogels by incorporating metal species into silica and alumina aerogel platforms are presented. Three preparation methods are described: (a) the incorporation of metal salts into silica or alumina wet gels using an impregnation method; (b) the incorporation of metal salts into alumina wet gels using a co-precursor method; and (c) the addition of metal nanoparticles directly into a silica aerogel precursor mixture. The methods utilize a hydraulic hot press, which allows for rapid (&#60;6 h) supercritical extraction and results in aerogels of low density (0.10 g/mL) and high surface area (200-800 m2/g). While the work presented here focuses on the use of copper salts and copper nanoparticles, the approach can be implemented using other metal salts and nanoparticles. A protocol for testing the three-way catalytic ability of these aerogels for automotive pollution mitigation is also presented. This technique uses custom-built equipment, the Union Catalytic Testbed (UCAT), in which a simulated exhaust mixture is passed over an aerogel sample at a controlled temperature and flow rate. The system is capable of measuring the ability of the catalytic aerogels, under both oxidizing and reducing conditions, to convert CO, NO and unburned hydrocarbons (HCs) to less harmful species (CO2, H2O and N2). Example catalytic results are presented for the aerogels described.

Here we present protocols for preparing and testing catalytic aerogels by incorporating metal species into silica and alumina aerogel platforms. Methods for preparing materials using copper salts and copper-containing nanoparticles are featured. Catalytic testing protocols demonstrate the effectiveness of these aerogels for three-way catalysis applications.

快速超临界萃取制备催化气凝胶的制备与试验研究

Protocols for preparing and testing catalytic aerogels by incorporating metal species into silica and alumina aerogel platforms are presented. Three ...

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.

土壤样品多涨价可能分析的 MPLEx 协议

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

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.

用亚硫酸氢萃取协议分离混合物中的醛和反应性酮

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

Surface Functionalization of Metal-Organic Frameworks for Improved Moisture Resistance

Metal-organic frameworks (MOFs) are a class of porous inorganic materials with promising properties in gas storage and separation, catalysis and sensing. However, the main issue limiting their applicability is their poor stability in humid conditions. The common methods to overcome this problem involve the formation of strong metal-linker bonds by using highly charged metals, which is limited to a number of structures, the introduction of alkylic groups to the framework by post-synthetic modification (PSM) or chemical vapour deposition (CVD) to enhance overall hydrophobicity of the framework. These last two usually provoke a drastic reduction of the porosity of the material. These strategies do not permit to exploit the properties of the MOF already available and it is imperative to find new methods to enhance the stability of MOFs in water while keeping their properties intact. Herein, we report a novel method to enhance the water stability of MOF crystals featuring Cu2(O2C)4&#160;paddle-wheel units, such as HKUST (where HKUST stands for Hong Kong University of Science &#38; Technology), with the catechols functionalized with alkyl and fluoro-alkyl chains. By taking advantage of the unsaturated metal sites and the catalytic catecholase-like activity of CuII ions, we are able to create robust hydrophobic coatings through the oxidation and subsequent polymerization of the catechol units on the surface of the crystals under anaerobic and water-free conditions without disrupting the underlying structure of the framework. This approach not only affords the material with improved water stability but also provides control over the function of the protective coating, which enables the development of functional coatings for the adsorption and separations of volatile organic compounds. We are confident that this approach could also be extended to other unstable MOFs featuring open metal sites.

Robust functional catechol coatings were produced in one step by direct reaction of the material known as HKUST with synthetic catechols under anaerobic conditions. The formation of homogeneous coatings surrounding the entire crystal is ascribed to the biomimetic catalytic activity of Cu(II) dimers on the external surface of the crystals.

金属-有机框架的表面功能化改善防潮性能

Metal-organic frameworks (MOFs) are a class of porous inorganic materials with promising properties in gas storage and separation, catalysis and sensing. ...

Automation of a Positron-emission Tomography (PET) Radiotracer Synthesis Protocol for Clinical Production

The development of new positron-emission tomography (PET) tracers is enabling researchers and clinicians to image an increasingly wide array of biological targets and processes. However, the increasing number of different tracers creates challenges for their production at radiopharmacies. While historically it has been practical to dedicate a custom-configured radiosynthesizer and hot cell for the repeated production of each individual tracer, it is becoming necessary to change this workflow. Recent commercial radiosynthesizers based on disposable cassettes/kits for each tracer simplify the production of multiple tracers with one set of equipment by eliminating the need for custom tracer-specific modifications. Furthermore, some of these radiosynthesizers enable the operator to develop and optimize their own synthesis protocols in addition to purchasing commercially-available kits. In this protocol, we describe the general procedure for how the manual synthesis of a new PET tracer can be automated on one of these radiosynthesizers and validated for the production of clinical-grade tracers. As an example, we use the ELIXYS radiosynthesizer, a flexible cassette-based radiochemistry tool that can support both PET tracer development efforts, as well as routine clinical probe manufacturing on the same system, to produce [18F]Clofarabine ([18F]CFA), a PET tracer to measure in vivo deoxycytidine kinase (dCK) enzyme activity. Translating a manual synthesis involves breaking down the synthetic protocol into basic radiochemistry processes that are then translated into intuitive chemistry &#34;unit operations&#34; supported by the synthesizer software. These operations can then rapidly be converted into an automated synthesis program by assembling them using the drag-and-drop interface. After basic testing, the synthesis and purification procedure may require optimization to achieve the desired yield and purity. Once the desired performance is achieved, a validation of the synthesis is carried out to determine its suitability for the production of the radiotracer for clinical use.

Automation of a Positron-emission Tomography PET Radiotracer Synthesis Protocol for Clinical Production

Positron-emission tomography (PET) imaging sites that are involved in multiple early clinical research trials need robust and versatile radiotracer manufacturing capabilities. Using the radiotracer [18F]Clofarabine as an example, we illustrate how to automate the synthesis of a radiotracer using a flexible, cassette-based radiosynthesizer and validate the synthesis for clinical use.

用于临床生产的正电子发射层析成像 (PET) 放射性同位素示踪合成协议的自动化

The development of new positron-emission tomography (PET) tracers is enabling researchers and clinicians to image an increasingly wide array of biological ...