Employing Pressurized Hot Water Extraction (PHWE) to Explore Natural Products Chemistry in the Undergraduate Laboratory

A recently developed pressurized hot water extraction (PHWE) method which utilizes an unmodified household espresso machine to facilitate natural products ...

University of Tasmania

The partial reduction of pyrroles is not a common practice even though it offers a potential route to pyrroline building blocks, commonly used for synthesis. We have investigated the reduction of 2-acyl-N-sulfonylpyrroles and by varying the hydride source and solvent, achieved a chemoselective reduction, leading to 3-pyrrolines and alkyl pyrroles in high yield.

Chemoselective reduction of 2-acyl-N-sulfonylpyrroles: synthesis of 3-pyrrolines and 2-alkylpyrroles.

La r&eacute;duction partielle des pyrroles n&#39;est pas une pratique courante, m&ecirc;me si elle offre une voie potentielle pour les blocs de construction pyrroline, couramment utilis&eacute; pour la synth&egrave;se. Nous avons &eacute;tudi&eacute; la r&eacute;duction de 2-acyl-N-sulfonylpyrroles et en faisant varier la source de l&#39;hydrure et solvant, atteint une r&eacute;duction chimios&eacute;lective, conduisant &agrave; des pyrroles 3-pyrrolines et alkyle avec un rendement &eacute;lev&eacute;.

R&eacute;duction chimios&eacute;lective de 2-acyl-N-sulfonylpyrroles : synth&egrave;se du 3-pyrrolines et 2-alkylPyrrole.

Die partielle Reduktion des Pyrrols ist nicht &uuml;blich, obwohl es eine m&ouml;gliche Route zu Pyrroline-Bausteine, gew&ouml;hnlich f&uuml;r Synthese bietet. Wir haben untersucht, die Reduktion von 2-Acyl-N-Sulfonylpyrroles und durch Variation der Hydrid Quelle und L&ouml;sungsmittel, erreichte eine Reduzierung um chemoselektive, was zu 3-Pyrrolines und Alkyl Pyrrolringen in high-Yield.

Chemoselektive Reduktion der 2-Acyl-N-Sulfonylpyrroles: Synthese von 3-Pyrrolines und 2-Alkylpyrroles.

La riduzione parziale del pyrroles non &egrave; una pratica comune, anche se offre un potenziale percorso di pirrolina building blocks, comunemente utilizzato per la sintesi. Abbiamo studiato la riduzione di 2-acil-N-sulfonylpyrroles e variando la sorgente idruro e solvente, ottenuto una riduzione chemoselective, portando a 3-pyrrolines e alchil pyrroles nell&#39;alto rendimento.

Chemoselective riduzione di 2-acil-N-sulfonylpyrroles: sintesi del 3-pyrrolines e 2-alkylpyrroles.

&#x5421;&#x54AF;&#x90E8;&#x5206;&#x51CF;&#x5C11;&#x4E0D;&#x662F;&#x5E38;&#x89C1;&#x7684;&#x505A;&#x6CD5;&#xFF0C;&#x5373;&#x4F7F;&#x5B83;&#x63D0;&#x4F9B;&#x4E86;&#x5230;&#x54AF;&#x6784;&#x5EFA;&#x57FA;&#x5757;&#xFF0C;&#x901A;&#x5E38;&#x7528;&#x4E8E;&#x5408;&#x6210;&#x7684;&#x6F5C;&#x5728;&#x9014;&#x5F84;&#x3002;&#x6211;&#x4EEC;&#x8C03;&#x67E5;&#x51CF;&#x5C11; 2-&#x9170;&#x57FA;-N-sulfonylpyrroles &#x548C;&#x7531;&#x4E0D;&#x540C;&#x7684;&#x6C22;&#x5316;&#x7269;&#x53D1;&#x751F;&#x6E90;&#x548C;&#x6EB6;&#x5242;&#xFF0C;&#x5B9E;&#x73B0;&#x9009;&#x62E9;&#x6027;&#x8FD8;&#x539F;&#xFF0C;&#x5BFC;&#x81F4;&#x5728;&#x9AD8;&#x4EA7;&#x91CF;&#x7684; 3 pyrrolines &#x548C;&#x70F7;&#x57FA;&#x5421;&#x54AF;&#x3002;

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2-&#x30A2;&#x30B7;&#x30EB;-N-sulfonylpyrroles &#x306E;&#x5316;&#x5B66;&#x9078;&#x629E;&#x7684;&#x9084;&#x5143;&#xFF1A; 3 pyrrolines &#x3068; 2-alkylpyrroles &#x306E;&#x5408;&#x6210;&#x3002;

Pyrroles&#xC758; &#xBD80;&#xBD84; &#xAC10;&#xC18C; pyrroline &#xBE4C;&#xB529; &#xBE14;&#xB85D;, &#xD569;&#xC131;&#xC744; &#xC704;&#xD574; &#xC77C;&#xBC18;&#xC801;&#xC73C;&#xB85C; &#xC0AC;&#xC6A9; &#xB418;&#xB294; &#xC7A0;&#xC7AC;&#xC801;&#xC778; &#xACBD;&#xB85C; &#xC81C;&#xACF5; &#xD558;&#xC9C0;&#xB9CC; &#xC77C;&#xBC18;&#xC801;&#xC778; &#xC5F0;&#xC2B5; &#xD558;&#xC9C0; &#xC54A;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC; &#xC870;&#xC0AC; &#xADF8;&#xB9AC;&#xACE0; &#xC218;&#xC18C; &#xC18C;&#xC2A4; &#xBC0F; &#xC6A9; &#xB9E4;&#xB97C; &#xB2EC;&#xB9AC; &#xD558; &#xC5EC; 2 acyl N sulfonylpyrroles&#xC758; &#xAC10;&#xC18C;, &#xB192;&#xC740; &#xC218;&#xC728; 3 pyrrolines &#xBC0F; &#xC54C; &#xD0AC; pyrroles&#xB85C; &#xC774;&#xC5B4;&#xC9C0;&#xB294; chemoselective &#xAC10;&#xC18C;&#xB97C; &#xB2EC;&#xC131;.

2 Acyl N sulfonylpyrroles&#xC758; Chemoselective &#xAC10;&#xC18C;: 3 pyrrolines 2 alkylpyrroles&#xC758; &#xD569;&#xC131;.

La reducci&oacute;n parcial de pirroles no es una pr&aacute;ctica com&uacute;n, aunque tambi&eacute;n ofrece una ruta potencial para bloques pyrroline com&uacute;nmente utilizado para la s&iacute;ntesis. Hemos investigado la reducci&oacute;n de 2-acil-N-sulfonylpyrroles y variando la fuente de hidruro y solvente, logr&oacute; una reducci&oacute;n de estereoselectiva, llevando a 3-pyrrolines y Alquilo pirroles de alto rendimiento.

Reducci&oacute;n estereoselectiva de 2-acil-N-sulfonylpyrroles: s&iacute;ntesis de pyrrolines-3 y 2-alkylpyrroles.

The oxidation of pyrroles usually leads to uncontrolled polymerization and decomposition. To overcome this problem, the controlled oxidation of substituted pyrroles with Dess-Martin periodinane is reported. This strategy yields a range of 5-aroyloxypyrrolinones.

Controlled oxidation of pyrroles: synthesis of highly functionalized γ-lactams.

A new, practical, rapid, and high-yielding process for the pressurized hot water extraction (PHWE) of multigram quantities of shikimic acid from star anise (Illicium verum) using an unmodified household espresso machine has been developed. This operationally simple and inexpensive method enables the efficient and straightforward isolation of shikimic acid and the facile preparation of a range of its synthetic derivatives. 

New method for the rapid extraction of natural products: efficient isolation of shikimic acid from star anise.

Polygodial, a valuable sesquiterpene dialdehyde featuring an epimerizable stereocenter was efficiently extracted and isolated in gram-scale quantities (3.3% w/w) from Tasmannia lanceolata (Tasmanian native pepper) via a recently developed rapid pressurised hot water extraction (PHWE) technique that utilises an unmodified household espresso machine. This method was compared to the maceration of T. lanceolata under a range of conditions. Polygodial was used to achieve semi-syntheses of closely related sesquiterpene natural products drimendiol, (-)-drimenol, (+)-euryfuran, and some non-natural derivatives. 

Practical isolation of polygodial from Tasmannia lanceolata: a viable scaffold for synthesis.

Bitter Melon (BM) has been used as a functional food in traditional Chinese and Indian medicine for many generations and has gained a great deal of attention due to its apparent benefits in moderating some of the pathogenic processes in a variety of inflammatory conditions. BM extract (BME) has been shown to possess strong anti-oxidant properties. In addition, it can ameliorate oxidative stress and potentially ER stress. There is increasing evidence that oxidative and ER stress are major contributors for intestinal secretory cell dysfunction which leads to local inflammation and disease pathogenesis that are hallmarks of inflammatory bowel diseases (IBD). Hence, the search for potential therapeutics against ER stress and oxidative stress in intestinal epithelial secretory cells may provide valuable resources for the management of IBD. The aim of the present study was to investigate the effects of BME in ameliorating ER stress in colonic epithelial cells.

Bitter melon protects against ER stress in LS174T colonic epithelial cells.

Polygodial, a drimane sesquiterpenoid dialdehyde isolated as a pungent component of the water pepper Persicaria hydropiper, exhibits antifeedant, antimicrobial, anti-inflammatory and anticancer effects. Polygodial also activates transient receptor potential vanilloid subtype 1 (TRPV1) channels. Previously, we described the synthesis of a C12-Wittig derivative of polygodial, termed P3, with significant antiproliferative effects against multiple cancer types including oral squamous cell carcinoma (OSCC). In the present study, a more potent derivative, P27, with superior anti-proliferative effects in vitro and antitumor effects in Cal-27 derived xenografts is described. Polygodial, P3, and P27 all significantly decreased OSCC tumor growth, with P27 being equipotent with polygodial and P3 being the least efficacious. However, neither analog elicited the adverse effect observed with polygodial: Profound transient inflammation. Although P3 and P27 pharmacophores are based on polygodial, novel effects on OSCC cell cycle distribution were identified and shared anticancer effects that are independent of TRPV1 activity were observed. Polygodial elicits an S-phase block, whereas P3 and P27 lead to G2/M phase arrest. Pretreatment of OSCC cells with the TRPV1 antagonist capsazepine does not affect the antiproliferative activity of P3 or P27, indicating that TRPV1 interactions do not regulate OSCC cell proliferation. Indeed, calcium imaging studies identified that the analogs neither activate nor antagonize TRPV1. Behavioral studies using a rat model for orofacial pain confirmed that these analogs fail to induce nocifensive responses, indicating that they are non-noxious in vivo. All compounds induced a significant concentration-dependent decrease in the mitochondrial transmembrane potential and corresponding apoptosis. Considering that P27 is equipotent to polygodial with no TRPV1-associated adverse effects, P27 may serve as an efficacious novel therapy for OSCC.

Jeremy Just

School of Natural Sciences - Chemistry

University of Tasmania

Employing Pressurized Hot Water Extraction (PHWE) to Explore Natural Products Chemistry in the Undergraduate Laboratory

Jeremy Just

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}School of Natural Sciences - Chemistry

University of Tasmania

Employing Pressurized Hot Water Extraction (PHWE) to Explore Natural Products Chemistry in the Undergraduate Laboratory

School of Natural Sciences - Chemistry