Negamycin

Naturally occurring chiral compounds provide an enormous range and diversity of possible starting materials. To be useful in asymmetric synthesis, they should be readily available in high enantiomeric purity. For many applications, the availability of both enantiomers is desirable. Many chiral molecules can be synthesized from natural carbohydrates or amino acids. The syntheses of (+)-exo-brevicomin (66) and negamycin (67) illustrate the application of such naturally occurring materials. 

Negamycin (67), a broad-spectrum antibiotic produced naturally by Strep-tomycespurpeofuscus, has also been synthesized from glucose (Fig. 1-29)85 ... 

The unsaturated ester-aldehyde 79 was also used for the synthesis of methyl 3,6-bis(acetamido)-2,3,4,6-tetradeoxy-a-DL-fhreo-hexo-pyranoside40 (87), an intermediate for the synthesis of negamycin and of methyl 3-N-acetyM-deoxy-a-DL-daunosaminide41 (88). 

Also ( Rj-fl- Lys 4 is found to be a substructure of several antibiotics. Examples are the hydrazinodipeptide negamycin 26 from Streptomyces purpeofuscus, bellenamine 28 from Streptomyces nashvillensis (Actinobacteria), and sperabillins A-D 25 from Pseudomonas Jluorescens (Proteobacteria). 

The /rflm -/V-silylated tetrahydro-2//-l, 3-oxazin-2-one 27 (R = TBDMS) has been utilized in the synthesis of (+ )-negamycin (28)15, a compound which shows a strong inhibitory activity against Gram-negative bacteria. 

Recently, analogous nitrones have been used by others in the synthesis of (2S)-4-oxopipecolic acid [45] and (-l-)-negamycin [46]. Chiacchio et al. [47] applied the Vasella-type nitrone 53 in an enantioselective synthesis of isoxazolidinyl thymine 55 (Scheme 10.18). As illustrated, the A-furanosyl nitrone 53 reacted with vinyl acetate to give a 1 1 mixture of two isoxazolidines 54 epimeric at C-5. In contrast to the poor cw/tran -diastereoselectivity, the diastereofacial selectivity... 

Miscellaneous Antibiotics - Other primarily antibacterial antibiotics reported in 1978 are listed in Table Structural work was also published for the following previously reported compounds mlmosamycin (59) grlseorhodin C (60) ristomycin A,"" striatin A (61), ° Isochelocardin (62), pseudomonic acid A (63). and rlfamycln R.Marine sources have been used to obtain the new antimicrobial metabolites 64 and 65. Syntheses of racemic negamycin and its analogs were reported. ... 

Kasahara, K, lida, H, Kibayashi, Ch., Asyimnetric total synthesis of (+)-negamycin and (—)-3-epinegamycin via enantioselective 1,3-dipolar cycloaddition, J. Org. Chem., 54, 2225-2233, 1989. 

Furanomycin has been shown to have the structure (35) by a synthesis from 2,5-anhydro-L-idose, which is summarized in Scheme 5. The quino-glycosides (36), which are bacteriocides and fungicides, have been synthesized by condensation of 2-methyl quinolinuim salts with peracetylated aldoses. The synthesis of the aminohexonhydrazide antibiotic negamycin is covered in Chapter 8,... 

A similar approach was taken to the synthesis of (+)-Negamycin Palladium(ll) assisted alkylation of the optically active enamide 15 followed by carbonylation with CO, and a vinyl trimethyltin afforded the intermediate 19 (Scheme 13). 

Some alkylpaUadium species may withstand the /3-hydrogen elimination and provide the carbonylative cross-coupling product in a reasonable yield (Scheme 12). The product was used for the total synthesis of (+)-negamycin. 

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