Macrolide antibiotics antitumor activity

S. antibioticus produces another unusual macrolide antibiotic [45] called chlorothricin (57) containing, in addition to the aglycone (modified methylsalicylic acid), saccharides, dideoxyhexoses in the first place. Their biosynthesis was investigated by the incorporation of stable isotopes [45-47]. The compounds were only active in a synthetic medium and inactive in a complex one [48]. Compounds designated MC031-034 (58-61) are similar to chlorothricin mentioned above and were isolated from the cultivation broth of Streptomyces sp. collected in Japan. Another compound, 2-hydroxychlorothricin (62), with antitumor activity, was isolated [66] from Streptomyces K818. 

Miller and co-workers reported a seminal work in the field of site-selective functionalization of biologically active polyol natural products by non-enzymatic protocol (Fig. 10). They reported that acylation of a polyol macrolide antibiotic, erythromycin A, took place first at C(2 )-OH and second at C(4")-OH by treatment with 2.0 equiv. of acetic anhydride in the presence of iV-methyl imidazole. These two hydroxy groups seem to be intrinsically most reactive. On the other hand, the second acylation took place at C(ll)-OH selectively when peptide-based catalysts 32 was used (Fig. 10) [36]. Thus, catalyst-controlled reversal of the site-selectivity in the acylation of biological active polyol natural products was achieved for the first time by non-enzymatic protocol. This strategy was further applied to site-selective diversification of apoptolidin A with antitumor activity [37]. 

The resorcinylic macrolides (also known as resordnylic add lactones or RALs) are a family of naturally occurring homologous macrolides. They are derived from polyketide biogenesis in different fungi and have been isolated from different fungal strains [12]. They have unique chemical structures and potent biological activities (antitumoral, antibiotic, and antimalarial activities) [13]. 

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