Directly Linked Polyazoles: Important Moieties in Natural Products

Abstract

Directly linked 1,3-azoles are found as substructures in important naturally occurring products that have interesting biological activities as well as fascinating structures. Therefore, many research groups are working on their total syntheses. Although new approaches have been developed to prepare these targets, classical 1,3-azole formation methodologies are still being used for this purpose. This report provides an overview of polyazole-containing natural products and the different strategies for the synthesis of directly linked 1,3-azole moieties.

From Amino Acids to Heteroaromatics—Thiopeptide Antibiotics, Nature's Heterocyclic Peptides

“…[35,36] One of the most common strategies involves the heterocyclization of serine or threonine side chains onto an amide carbonyl group to give an oxazoline that is subsequently oxidized to the oxazole, thereby mimicking the most likely biogenesis of the heteroaromatic ring. [17,34] A number of reagents have been employed to effect the cyclodehydration step, [37] for example, DAST, Deoxo-Fluor, Burgess reagent, SOCl 2 followed by AgOTf, or Mitsunobu conditions.…”

Palladium‐katalysierte dehydrierende Kreuzkupplungen von Benzazolen mit Azolen

“…[8] Obgleich zahlreiche Naturstoffe mit wichtigen biologischen Aktivitäten direkt verknüpfte Azolringe enthalten, ist die 2,2'-Verknüpfung von Azolen ein in der Natur selten anzutreffendes Motiv. [9] Der einzige prominente Vertreter ist dLuciferin, das von Glühwürmchen genutzt wird, um Oxyluciferin in einem elektronisch angeregten Zustand zu erzeugen (Schema 1). Bei seiner Rückkehr in den Grundzustand emittiert Oxyluciferin Licht im Wellenlängenbereich von 530 bis 640 nm (Biolumineszenz).…”

Palladium-catalyzed coupling reactions for the preparation of concatenated azoles

“…1 Some of these include: hennoxazole A (antiherpes), isolated from the sponge polyfibrospongia; telomestatine, a chemotherapeutic agent that inhibits telomerase and shows a correlation between its activity and tumor growth; leucamide A, isolated from the Australian sponge Leucetta microraphis with cytotoxic activity; ulupualide A, which has an unusual range of biological activities, such as cytotoxic and antifungal properties, and participates in cell proliferation in leukemia; and finally, merchercharmycin and some of its reported analogs, which have shown cytotoxic activity against cancer cells. A great effort has been put into the synthesis of oxazole-containing compounds, because of the broad spectrum of biological activity.…”

“…A great effort has been put into the synthesis of oxazole-containing compounds, because of the broad spectrum of biological activity. [1][2][3][4] Transition metal-catalyzed cross-coupling reactions have emerged as a powerful synthetic tool that allows a wide range of cross-coupling partners to be combined efficiently. 5 This method has been used for C-C bond formation in many synthetic procedures.…”

“…The metalation of ethyl oxazole-4-carboxylate 8 was also tested for cross-coupling reactions because the possibility of the posterior transformation of the ester into a new azole ring is well known. 1 The metalation of 8 was performed with LDA instead of n-BuLi to avoid side reactions with the ester group. However, the same reaction conditions with ZnCl 2 to afford 9 and posterior addition of 4-iodoanisole gave only starting material (Scheme 3).…”