Thiazoles from Oxazoles

With short periods of irradiation (with high-pressure mercury lamps) under oxygen in chloroform containing methylene blue as a sensitizer, variously substituted 2-arylthiazoles are converted in the corresponding 2-aryloxazoles (823). 

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Potassium tert-butoxide Thiazole from oxazole ring... 

The oxidation state of thiazolines and oxazolines can be adjusted by additional tailoring enzymes. For instance, oxidation domains (Ox) composed of approximately 250 amino acids utilize the cofactor FMN (flavin mononucleotide) to form aromatic oxazoles and thiazoles from oxazolines and thiazolines, respectively. Such domains are likely utilized in the biosynthesis of the disorazoles, " diazonimides, bleomycin, and epothiolone. The typical domain organization for a synthetase containing an oxidation domain is Cy-A-PCP-Ox however, in myxothiazol biosynthesis one oxidation domain is incorporated into an A domain. Alternatively, NRPSs can utilize NAD(P)H reductase domains to convert thiazolines and oxazolines into thiazolidines and oxazolidines, respectively. For instance, PchC is a reductase domain from the pyochelin biosynthetic pathway that acts in trans to reduce a thiazolyinyl-Y-PCP-bound intermediate to the corresponding thiazolidynyl-Y-PCP. ... 

In NRPS, the cyclization domain catalyzes cyclization of the side-chain nucleophile from a dipeptide moiety such as AA-Ser or AA-Cys (AA = amino acids) to form a tetrahedral intermediate, followed by dehydration to form oxazolines and thiazolines (Scheme 7.1) [20]. The synthesis of a 2-methyl oxazoline from threonine follows a similar mechanism. Once a heterocycle is formed, it can be further modified by reductase to form tetrahydro thiazolidine in the case of pyochelin biosynthesis. Conversely, oxidation of the dehydroheterocycles lead to heteroaro-mahc thiazoles or oxazoles as in the case of epothilone D (Figure 7.2) [21]. 

An alternative mechanism to form thiazoles and oxazoles is through oxidation of a dipeptide followed by cyclization from an enolate or thienolate precursor and subsequent dehydration (Scheme 7.2). This represents a higher-energy pathway and there is no accumulation of thiazoline or oxazoline intermediates [22-24]. 

Synthesis of imidazoles, oxazoles and thiazoles from acylamino ketones 569... 

Other five-membered heterocycles such as thiophenes, thiazoles and oxazoles have been successfully annellated in the anthraquinone series. For example, the yellow dye (12) may be prepared from 2,6-diaminoanthraquinone by condensation with benzotrichloride and sulfur. Similarly, the six-membered heterocycles acridines, quinoneazines, pyrazines, acridones and pyrimidines are frequently incorporated (B-52MI11201). In fact, the best known of the anthraquinone vat dyes are indanthrone (13) and flavanthrone (14). The former anthraquinoneazine, a beautiful blue, which was the first such structure to be manufactured on a large scale, may be prepared by alkali fusion of 2-aminoanthraquinone at 220 °C (27MI11200). Treatment of 2-aminoanthraquinone in nitrobenzene with antimony pentachloride yields the yellow flavanthrone (14), the structure being confirmed by Scholl (07CB1691). Both indanthrone and flavanthrone and their derivatives have attracted considerable commercial attention. 

Violene Radicals from Oxazoles, Thiazoles, and Selenazoles... 

The three 1,3-azoles, imidazole, thiazole and oxazole, are aU very stable compounds that do not autoxidise. Oxazole and thiazole are water-miscible liquids with pyridine-like odours. Imidazole, which is a solid at room temperature, and 1-methylimidazole are also water soluble, but are odourless. They boil at much higher temperatures (256 °C and 199 °C) than oxazole (69 °C) and thiazole (117 °C) this can be attributed to stronger dipolar association resulting from the very marked permanent charge separation in imidazoles (the dipole moment of imidazole is 5.6 D cf. oxazole, 1.4 D thiazole, 1.6 D) and for imidazole itself, in addition, extensive intermolecular hydrogen bonding. The dihydro- and tetrahydro-1,3-azoles are named imidazoline/imidazolidine, thiazoline/thiazolidine and oxazoline/oxazolidine. 

The cyclamides are small cyclic peptides that characteristically contain multiple thiazole, thiazoline, oxazole, and oxazoline rings, which are derived from cysteine, serine, and threonine residues. Some of the first examples of this class to be described were the patellamides (53-55) from the tunicate Lissoclinum patella, although it was later determined they were produced by the symbiotic cyanobacterium Prochloron sp. The structures were solved by a combination of acid hydrolysis and GC analysis, coupled with 2D NMR. Smaller cyclic peptides from this class include the hexapeptides westiellamide (56) and microcyclamide (57) from M. aeruginosa Many members of the class possess cytotoxic properties, although their biological function or mechanism of action is not fully understood. In contrast to many cyanobacterial peptides, aside from the unusual heterocyclic residues, these peptides generally contain only ribosomal amino acids. 

Only oxazole, of the trio, does not play any part in normal biochemical processes, though there are secondary metabolites (especially from marine organisms) which incorporate thiazole (and oxazole) units - the antibiotic cystothiazole A, from the myxobacterium Cyctobacter fuscus is an example. Imidazole occurs in the essential amino acid histidine histidines within enzymes are intimately involved in catalysis requiring proton transfers. The structurally related hormone, histamine, is a vasodilator and a major factor in allergic reactions such as hay fever. The thiazolium ring is the chemically active centre in the coenzyme derived from thiamin (vitamin B,). 

Synthesis of oxazoles and thiazoles from corresponding oxazolines and thiazohnes by dehydrogenation using the bromotrichloromethane (BrCCl3)-DBU system was reported by Williams et al. [38]. This transformation was apphed to synthesize many natural products. Doi and Takahashi reported the synthesis of telomestatin (124) [39], which has a macrocyclic polyoxazole structure. Reaction of oxazoline 122 with BrCCls-DBU gave trisoxazole 123 (Scheme 7.27). This left-hand segment was employed for the synthesis of telomestatin 124. 

Continuous study of oxyacetamide chemistry shifted research from the paddy herbicide to an upland herbicide with increasing water solubility that is suitable for such upland use. To this end, benzanellated analogues such as the benzothia-zole moiety of mefenacet were changed to simple five-membered heterocycles that contain at least one nitrogen atom to increase water solubility, and sulfur or oxygen atom to decrease lipophilicity, for instance thiazoles, thiadiazoles, oxazoles and oxadiazoles (Fig. 8.2). Consequently, many patent applications of the new class of heteroxyacetamide herbicides were disclosed [17, 18]. 

Kuriyama, Akaji, and Kiso used the Hantzsch thiazole synthesis in their convergent synthesis of (-)-mirabazole Mirabazole alkaloids have a unique architecture consisting of thiazoline, thiazole and oxazole rings, and have been shown to exhibit a diverse array of biological activities. Reaction of 156, prepared in 12 steps from D-alanine with chloroacetone 9 in refluxing ethanol, gave (-)-mirabazole B in 57% yield. 

By altering the solvent to dioxane from DMF, allyltriphenyl-starmane could be used to phenylate thiazoles and oxazoles in modest to good conversions although longer reaction times were required (eq 21). 

Thiazole and oxazole alkaloids Isolation and synthesis. Davyt, D., Serra, G. (2010) Mar. Drugs, 8, 2755-2780. Antitumor compounds from marine actinomycetes. Olano, C., Mendez, C., Salas, J.A (2009) Mar. Drugs, 7, 210-248. 

Raveh, A., Moshe, S., Evron, Z., Flescher, E., and Carmeli, S. (2010) Novel thiazole and oxazole containing cyclic hexapeptides from a... 

Mercaptoselenazoies with Q to C,o cyclic hydrocarbon substituents in the 4-position have been mentioned as giving negative images from photosolubie emulsions (38. 39). Equally cited are other heterocycles such as thiazole. oxazole, or imidazole. 

Selenium heterocycles receive far less mention in the literature than do such homologs as oxazole, thiazole, or imidazole. In fact, preparative methods of selenium heterocycles are much more limited than for the other series, mainly because of manipulatory difficulties arising from the toxicity of selenium (hydrogen selenide is even more toxic) that can produce severe damage to the skin, lungs, kidneys, and eyes. Another source of difficulty is the reactivity of the heterocycle itself, which can easily undergo fission, depending on the reaction medium and the nature of the substituents. 

Pyrazoles and imidazoles carrying a substituent on nitrogen, as well as oxazoles, thiazoles, etc., are converted by alkyl halides into quaternary salts. This is Illustrated by the preparation of thiamine (89) from components (87) and (88). 

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