Oxazoles ring synthesis

Formation of the oxazole ring is not always the last step in synthesis of the brightener. Unsymmetrical compounds that contain both a benzoxazole group and an ethene linkage can be prepared by the anil synthesis [51], in which a compound possessing an activated methyl group reacts with a Schiff base. The preparation of brightener 11.31 is an illustration of this method (Scheme 11.12). 

Isocyanides are useful reagents for the preparation of oxazoles unsubstituted at C-2. For example, TosMIC was used to generate the oxazole ring in a synthesis of phthoxazolin A 37 <990L1137>. However in the reaction of IV-tosyl aldimines with the isocyanide 38 the oxazoles that were isolated were 2 1 adducts 39 that had been further substituted at C-2 <98T12445>. 

One of the most reliable methods for constructing the oxazole ring is the cyclodehydration of a-acylamino ketones, the Robinson-Gabriel synthesis (1909/1910) (equation 93). The reaction is usually conducted in the presence of sulfuric add or phosphorus pentachloride and more recently polyphosphoric add, phosgene or anhydrous hydrogen fluoride have... 

N—C—O + C—C. The construction of the oxazole ring by the condensation of a-halogeno ketones with primary amides (equation 122) is the Bliimlein-Lewy synthesis (1884/1888). The method succeeds best when the resulting oxazole contains one or more aryl substituents. The use of formamide leads to oxazoles with a free 2-position and in this case it is possible that the reaction proceeds as in equation (113). 2-Aminooxazoles are produced by the action of a-halogeno ketones on urea and its derivatives (equation 123) or on cyanamide (80ZOR2185). The mercury(II) sulfate-catalyzed condensation of alkynic alcohols or their esters with primary amides leads to trisubstituted oxazoles (equation 124). 

T10425>. Through a proper use of the Suzuki-Miyamura and van Leusen oxazole synthesis it was possible to synthesize a wide variety of aromatic derivatives substituted with oxazole rings. The strategy was based on the initial synthesis of the aromatic scaffold and the subsequent reaction of the carbonyl functions with toluenesulfonylmethyl isocyanide (TosMIC) as depicted in the following scheme<07S3653>. 

A library of cyclic peptides was obtained by the cyclooligomerization of mixtures of azole-based amino acids. This synthetic approach was applied to the synthesis of bistratamide H and didmolamide A, cyclic peptides containing oxazole rings <07OBC1541>. Other cyclic scaffolds based on oxazole peptides were published <07EJO1779 07T9862 07NAR3272>. 

A new synthesis of (-)-ulapualide A was completed by the group of Pattenden following a previous synthesis of a different diastereisomer whose chiroptical and H NMR spectroscopic data were identical with those of the natural product <07 AG(E)4359>. The first synthesis of siphonazole 119 was completed. Both the oxazole rings were constructed using rhodium carbene chemistry <07CC1508>. 

The synthesis of the oxazole compound 45 starts with the coupling of the N-protected (/ )-methylcysteine compound 18 with threonine terf-butyl ester using bis(2-oxo-3-oxazolidi-nyl)phosphinyl chloride (BOP-Cl) [15] as a coupling reagent. Jones oxidation of the threonine hydroxy group leads to the ketoamide 44. The desired oxazole ring is closed by treatment with thionylchloride/pyridine. After deprotection, the oxazole, compound 45 is obtained. In the next step the oxazole compound 45 is coupled with the tris(thiazoline) compound 43 to yield the thioester 46. Now Fukuyama closes the fourth and last thiazoline ring (46 47). After conversion of the carboxylic acid function into a methyl-... 

Credico et al. [13] gave the selective synthesis of 2-substituted-4-carboxy oxazoles (i). They optimized the mild and selective procedure so that the 2-substituted-4-carboxy derivatives can be obtained in multi-gram scale. Ball et al. [14] synthesized the various triazole derivatives (ii), bearing the oxazole ring system via a tandem alkylation/cyclisation reaction, exploiting a facilitating dummy bromine atom. 

Titanium(rv)-mediated tandem deprotection-cyclodehydration of a protected cysteine A -amide was used in the synthesis of thiazolone- and thiazole-containing heterocycles as building blocks for macrocycle synthesis <20000L3289>. Similarly, the directly connected thiazole-oxazole ring system present in microcin B17 was synthesized from aminoacetonitrile hydrochloride <1996JOC778>. 

The total synthesis of the antiviral marine natural product (-)-hennoxazole A was accomplished by F. Yokokawa and co-workers." The mild reduction of a secondary alkyl azide at C9 was carried out using triphenylphosphine in a THF/water mixture at slightly elevated temperature. The corresponding primary amine was obtained in good yield and was subsequently acylated and converted to one of the oxazole rings of the natural product. 

Compounds having a linear fusion of four or five successive 2,4-disubstituted thiazoline oxazole rings are important because of their antiviral activities. Among these compounds are tantazoles which exhibit an unusual cytotoxic activity <90JA8195>. The structure of tantazoles have been revised <93TL668l> and in some cases like tantazole B (460) the absolute configuration has been established by total synthesis <93JA8449>. 

Some new procedures for the introduction of the preformed oxazole ring into more complex stmctures were described mainly in studies aimed at the synthesis of natural product such as ajudazol A <050L1063>, martefragin A <05JOC5840>, diazonamide A <05JOC7305>, cyclopeptide YM-216391 <05CC797>. 

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