Oxazoles naturally occurring

The mold metabolite, pimprinine (268), obtained from Streptomyces pimprina, is another naturally occurring oxazole.427 

Karimoto, B. Axelrod, J. Wolinsky, and E. D. Schall, Tetrahedron Lett., 83 

Technische Hochschule fur Chemie Carl Schorlemmer Lmna-Merseburg, Sektion Verfahrenschemie, Merseburg, German Democratic Republic 

Amine Ar-imines are derived formally from tertiary amines by replacing the free pair of electrons by an imino group. Aliphatic, aromatic, or heteroaromatic compounds are obtained according to the nature of the amine. Heteroaromatic JV-imines are derived from heterocyclic compounds containing an azomethine nitrogen atom in the molecule. 

The A-imines are members of the isoelectronic and isosteric series A-oxides, Ar-imines, and A-ylids (formulas 1-3). Whereas the A-oxides1 2 and the A-ylids3-6 have been reviewed several times, a detailed review of A-imines6 was published only recently see also a brief summary in Sisler et al.7 Thus information is sparse for the amine A-imines, in contrast with the other members of the isosteric series. 

---

Fig. 1 Naturally occurring oxazole- and thiazole-containing macrocycles...

The imidazole ring occurs naturally in histamine 3.5, an important mediator of inflammation and gastric acid secretion. A quaternised thiazole ring is found in the essential vitamin thiamin 3.6. There are few naturally occurring oxazoles, apart from some secondary metabolites from plant and fungal sources. 

Naturally occurring oxazoles are derived from enzymatic post-translational modifications of peptide-based precursors <1999NPR249>. The oxygen functionality on the side chain of A -acylated serines (R = H) and threonines (R = Me) 307 is capable of undergoing heterocyclization onto the preceding carbonyl group to create five-membered saturated heterocycles 308 (Scheme 86). Dehydration followed by two-electron oxidation results in aromatic oxazoles 309. 

The last section includes syntheses of some naturally occurring oxazoles. The choice of these natural products is arbitrary and selected from the recent literature to demonstrate the versatility of oxazoles in synthesis. For more complete discussions of oxazole natural products the reader is referred to specialized... 

The structural diversity and complexity of naturally occurring oxazoles (see Section 1.5) has fueled a continuing search for mild, efficient methods of oxazole... 

The reaction of acyl halides with phosphazenes gives an mild method for the preparation of 2,5-disustituted oxazoles." This method has been used in the preparation of naturally occurring oxazole alkaloids, such as pimprinine analogues 35a, ° 0-methylhalfordinol (35b) and annuloline (35c). ° The preparation of five pimprinine analogues through... 

Substituted binaphthyl compounds can be synthesized in high optical yields using nucleophilic aromatic substitution reactions in which the chiral leaving groups are alkoxy moieties derived from naturally occurring alcohols28-29. For example, the condensation of 2-(l-alkoxynaphth-2-yl)-4.5-dihydro-4,4-dimethyl-l,3-oxazole with 1-naphthyllithium or 2-methoxy-l-naphthyl 2-magnesium bromide leads to (ft)- or (.S)-(l,T-binaphthyl-2-yl)-4,5-dihydro-4,4-dimethyl-l,3-oxazole derivatives. 

Thirty-four naturally occurring compounds that incorporate the oxazole moiety have been isolated thus far. The sources are diverse—plants of the families Gramineae and Rutaceae, nudibranch egg masses, and microorganisms, the latter having furnished the majority of the compounds. With three exceptions, the marine and bacterial oxazoles appear to have been formed from peptides of aliphatic amino acids, while the oxazoles of the Gramineae and Rutaceae arise from the chorismic acid-phenylalanine pathway. The oxazoles have not been... 

Oxazoles are well-investigated compounds. The occurrence, uses, and synthesis of oxazole derivatives have been the subjects of extensive reviews.5 The heterocyclic oxazole unit is seen with various substitution-patterns in a large number of naturally occurring compounds. Furthermore, oxazoles serve as synthetic intermediates leading to many other systems.5 6 7 In this context, oxazoles have seen, for example, numerous applications as "2-azadiene" components in 4+2 cycloadditions with several types of dienophiles. Further transformations of the products then lead to a number of other nitrogen- or oxygen-containing heterocyclic products.6... 

The lithiation of isophthalic acid can be achieved either at 2- or 4- position after conversion of the carboxylic acid groups to oxazole derivatives or N,N -butylamide derivatives respectively. Conversion to N-methyl amide derivative leads to the precipitation of the N-lithio salt on treatment with BuLi which fails to lithiate further. The N-lithio salt of the N-butylamide, however, remains in solution under the experimental conditions. It may be noted that the two lithiation reactions furnish two different carboxydihydroisocoumarins. The 5-carboxy dihydroisocoumarin can be converted to erythrocentaurine, which is naturally occurring... 

Thiopeptide antibiotics, thiazolyl peptides, naturally occurring sulfur-containing, highly modified, macrocyclic peptides. They share a number of structural motifs, including several heterocycles such as thiazoles, a dehydropiperidine, a pyridine, oxazoles, and indoles. Nearly aU of the thiopeptide antibiotics act as inhibitors of protein synthesis in bacteria. They are secondary metabolites produced by actino-mycetes, largely by the genus Streptomyces. A representative member of this family is thiostrepton [M. C. Bagleyetal., Chem. Rev. 2005, 105, 685]. 

Masamune and co-workers ° reported the first synthesis of naturally occurring (—)-calycuIin A, 1189a. An earlier report" focused specifically on construction of a fully elaborated oxazole containing a C(26)-C(37) fragment 1322 and the intermediates 1363 and 1364 (Scheme 1.349). Note that the configurations of 1363, 1364, and 1369 correspond to those present in nt-1189a (i.e., (+)-... 

Natural pristinamycin II is a mixture of two polyunsaturated macrolactones which differ in the level of oxidation of the proline residue. The major component, pristinamycin 11 (33), possesses a dehydroproline ring, which is replaced by a (i )-proline residue in the minor component, pristinamycin Ilg (34). The ratio of these two compounds in the natural mixture varies from 90 10 to 97 3 depending on the fermentation conditions and the strain of Streptomyces. The pristinamycin II components also contain an oxazole nucleus incorporated into the macrolactone structure, which is relatively uncommon in naturally occurring compounds. 

D. Kumar, S. Sundaree, G. Patel, V.S. Rao, A facile synthesis of naturally occurring 5-(3-indolyl)oxazoles, Tetrahedron Lett. 49 (2008) 867-869. 

---