Aplasmomycins

The antibiotic aplasmomycin serves as a receptor or transporter for borate. Retrosynthetic simplification of the boron-free macrocycle to identical hydroxy acid subunits is clearly appropriate. Further retrosynthetic dissection produced fragments A, B and oxalate and provided a workable synthetic plan. 

Further elaboration of the MOM derivative E was carried out as described above for the MTM protected fragment B to afford fragment F which was converted to aplasmomycin by an 8-step sequence. 

Secondary metabolites generated via the propionate route are quite unusual in nature. Relevant exceptions are some antibiotic macrolides from Streptomycetes [42], but wholly propionate-derived macrolides are rare. This biosynthetic pathway has been well proved for erythromycin (13), where the aglycone is produced by assembling seven propionate units [43, 44], and for a few related antibiotics [45]. However, very sophisticated biosynthetic experiments [46] have established that some apparent propionate units in other macrolides (e.g., aplasmomycin [46]) from Streptomycetes could be formed either by C-methylation through S-adenosylmethionine or from glycerol. 

In contrast, the biosynthesis of aplasmomycin in the sea and boromycin on land are expected to follow much the san pathways since actinomycetales are involved in both cases (Chart 8.3.FA/PO). Macrolactams are common metabolites in actinomycetales (Chart 8.3.FA/PO), which, as symbionts, may accoimt for the presence of these metabolites also in marine demosponges. 

Macrolides boromvcin-like Mar. aplasmomycin from Streptomycesffiseus, Actinom., Bact. frmn Japan sea mud Land boromycin from African soil Streptomyces antibioticus, Actinom., Ba<4. Stout 1991 antimvcin-like Mar. and Land Streptomyces spp. Imamura 1993. 

Diatoms also require boron, which is incorporated into the silicon-rich cell walls.3 Some strains of Streptomyces griseus produce boron-containing macrolide antibiotics such as aplasmomycin (right).0 Recently a function in plant cell walls has been identified (see also main text) as crosslinking of rhamnogalacturonan portions of pectin chains by borate diol ester linkages as illustrated. 

The biosynthetic studies undertaken to date on microbial marine natural products well illustrate the diversity of metabolic pathways encountered in cultured marine bacteria. Examples include brominated alkaloids such as pentabromopseudiline (Structure 2.1),19 polyketide or mixed polyketide metabolites such as oncorhyncholide (Structure 2.2),20 aplasmomycin (Structure 2.3),21 and andrimid (Structure 2.4),22 or the cyclic depsipeptide salinamide A (Structure 2.5).23 As researchers continue to define more specific culture media and a wider range of marine bacteria from diverse habitats are successfully placed into culture, the true biosynthetic potential of these prolific and adaptable microorganisms can be explored. 

Unlike the terrestrial actinomycetes, marine actinomycetes have been shown to produce mac-rolides only rarely. One example of this class of compounds is the aplasmomycins A-C... 

---