Azirinomycin

Azirinomycin (129 Scheme 11.19) was isolated as a broad-spectrum antibiotic from Streptomyces aureus by workers at Merck, Sharp, and Dohme in 1971 [192,... 

H-azirine-2-carboxylate 80, 102 2H-azirine-2-phosphonate 104 2H-azirine-3-phosphonate 104 azirinomycin 435 azomethine ylide 25, 474... 

The same elimination strategy was used for the synthesis of the natural product (i )-(-)-dysidazirine 15 as is shown in Scheme 10 [23]. The requisite aziri-dine ester was prepared by treatment of sulfimine 19 with the lithium enolate of methyl bromoacetate. This reaction is a Darzens-type condensation leading to czs-M-sulfinylaziridine ester 20. The elimination of sulfenate was accomplished in the same manner as mentioned above (see Scheme 9). The natural product 15 (see Fig. 1) was obtained in 42% yield. Attempts to prepare azirinomycin 14 in a similar fashion all failed [23]. 

The azirine ring has also been found in several natural products. The first azirine-containing natural product isolated was Azirinomycin (140) <71JAN48>. More recently, the similar azirine-containing antibiotic Dysidazirine (141) was isolated and shown to possess cytotoxic and antibacterial activity <88JOC2103>. The synthesis of an aminoazirine-containing peptide (142) has been reported <93T467l>. 

The azirinomycin (12), 3-methyl-2H-azirine-2-carboxylic acid, was isolated from a strain of Streptomyces aureus. Its methyl ester (13) exhibited broad spectrum antibiotic activity in vitro against both Gram-positive and Gram-negative bacteria [33, 34]. The carboxylic acid (12) is most active against Staphylococcus aureus followed by Proteus vulgaris. Bacillus subtilis, and Streptococcus faecalis. In contrast, the methyl ester shows its lowest activities against one of the Staphylococcus aureus cultures and Streptococcus faecalis. 

Aziridine-2,3-dicarboxylic acid, 980 Aziridme-2,3-dicarboxylic acid, 980, 987 Aziridine ring, 978, 986, 1000 4-(l-Aziridinyl)-3-buten-2-one, 979 A-Aziridinylspermidine, 991 Azirinomycin, 979... 

First isolation of tbe natural product azirinomycin (a) E.O. Stapley, D. Hendlin, M. Jackson,... 

Azirines and Aziridines.— The photolysis and thermolysis of the azido ester (143) to the azirine (144) was described by Hassner and Fowler in 1968. A study of isomeric compounds (145) has now been described, leading to the tautomeric isomer (146) of the antibiotic azirinomycin (147). 3,5-Dimethylaminoisoxazoles (148) have been prepared by the addition of hydroxylamine to phosgene iminium salts. The photoisomerization of the 4-substituted isoxazoles (148) to the azirines (149) is already known, and a paper has now described the near-quantitative thermal... 

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