Bacterial Oxazoles

The bacterial oxazoles span a wide range in structural complexity. The most simple are the indolyl compounds pimprinine (70), pimprinethine (71), and pimprinaphine (72). All three compounds, which are colorless and crystalline, cooccur in Streptoverticillium olivoreticuli (28), with pimprinine (70) having 

The syntheses of Oikawa et al. (32, 33) are biomimetic in that DDQ was used to simulate the action of the then recently isolated crystalline hemoprotein from Pseudomonas known as tryptophan side chain a,3-oxidase (34). The natural products 70-72 as well as a number of related compounds were prepared by this method. N- Acetyltryptamine 76, on treatment with 2 equiv DDQ under anhydrous conditions, gave pimprinine (70) in only 10% yield (32). Reaction of the 

N-acyltryptamines 76-78 with DDQ in aqueous THF gave good yields of the 3-acylamido indoles 79-81 which were then cyclodehydrated to the natural products 70-72 (32). 

The mechanism of the DDQ oxidation under anhydrous conditions [shown for the formation of pimprinine (70)] is thought to involve dehydrogenation to 82 followed by intramolecular nucleophilic addition to form the dihydrooxazole 83 a second dehydrogenation yields intermediate 84 which isomerizes to the alkaloid 70. The low yield of 70 obtained from this reaction was rationalized on the 

For the preparation of 70-72 Koyama etal. (28) employed the 5-3 -(indolyl)-oxazole 88 obtained from ethylindole-3-carboxylate (87) and isocyanomethyl lithium. The oxazole 88 was refluxed in acetic anhydride—acetic acid or propionic anhydride-propionic acid to afford pimprinine (70) and pimprinethine (71) in 13 and 19% yield, respectively. Hydrolysis of these reaction mixtures and that produced with phenylacetic acid anhydride-phenylacetic acid gave high yields (84-92%) of the 3-acylamidoindoles 79-81, which could be smoothly cyclized with phosphorus oxychloride to the natural products 70-72 (28). 

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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... 

It has been hypothesized that the trisoxazole moiety in kabiramide C (64) arises by cyclization of the dehydrotriserine residue 65. This conjecture is consistent with the established mode of formation of the bacterial oxazole virginia-mycin Ml 90 from an acylserine (vida infra). A more recent suggestion is that the trisoxazole 69 may arise by cyclization of the Beckmann rearrangement product 68 of the trioxime 67 derived from the polyketide 66 (27). 

Among the indolyl bacterial oxazoles 70-72, pimprinine (70) has been reported to be antiepileptic (106). It has also been shown to possess monoamine oxidase inhibitory activity (107). 

Thiazole, (III), oxazole, imidazole, and pyrazole gyrase inhibitors prepared by Charifson (3) were effective against the bacterial DNA gyrase two B subunits and used in treating antibiotic resistance. 

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