Of aplasmomycin

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. 

Another useful reagent for macrolactonization via mixed phosphoric anhydride is N,N- bis(2-oxo-3-oxazolidinyl)phosphordiamidic chloride (BOP-Cl, 64), which was used by Corey and coworkers [41] in the first synthesis of aplasmomycin (67), a novel boron-containing macrocyclic antibiotic. As shown in Scheme 21, the linear precursor 65 was treated with 3 equiv of BOP-Cl (64) and 7 equiv of triethylamine in dichloromethane at 23 °C for 6 h to give the dilactone 66 in 71% yield. 

The structure of the Ag-salt of aplasmomycin was solved by an X-ray crystallographic analysis [46] and the structure of the aplasmomycin was further proved by and NMR spectra [47], It was found than the conformation of aplasmomycin in CDCI3 solution is identical to that in the solid state and that removal of the boron atom from aplasmomycin results in only a slight conformational change of the molecule. 

The three aplasmomycins (12-14) were compared in terms of antibacterial activity (Table 6), alkali metal ion selectivity (Table 7) and transport ability. The results summarized below show that the antibacterial activity of aplasmomycin B (13) was nearly equal to that of aplasmomycin, while aplasmomycin C (14) showed a weaker activity. It was also noted that the ability to form complexes with other metals does not directly correspond with antibacterial activity. Cation selectivity decreased in the order Rb > K > Cs = Na > Li. The three aplasmomycins did not show any affinity towards divalent cations. 

Table 7. Relative affinity of aplasmomycins for various cations...

The following elucidation of aplasmomycin biosynthesis was done with isotopically (D, T, C and labeled precursors. In the... 

Table 8. Effect of aplasmomycins on the methane production and the proportion of volatile acids in ruminants...

The animals were treated with an appropriate amount of aplasmomycins per day. 

The C-12 to C-17 segment (645) of ( + )-aplasmomycin has been synthesized from 590 as shown in Scheme 94 [148]. In the first step, an aldol condensation of isopropyl propionate enolate with 590 produces 638 as a mixture of isomers. After conversion to enone 640, reduction of the carbonyl with NaBH4-CeCl3 gives alcohol 641 as a single isomer. A second reduction of642 with zinc borohydride gives a separable mixture of isomers, the major isomer... 

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. 

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... 

A new boron containing antibiotic, aplasmomycin (12), was obtained from a strain of Streptomyces griseus isolated from shallow sea sediment in Sagami Bay, Japan [43, 44]. 

Aplasmomycin inhibits Gram-positive bacteria including mycobacteria in vitro, see also Table 5. Male mice were infected intraperitoneally by Plasmodium berghei and when aplasmomycin in peanut-oil was administered orally, the number of plasmodium-containing red cells decreased and all treated mice survived. It was on the basis of this potent antiplasmodium activity that aplasmomycin received its name. The acute toxicity in mice was 125 mg/kg by intraperitoneal injection. 

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