Actinamine

Eor shaping the 1,3-diaminocyclitol into its final configuration and into the actinamine structure, first an epimerization step has to invert the stereochemical placement of the 2-hydroxyl group, which is proposed to be catalyzed by the SpcD enzyme, being related to sugar epimerases second, the actinamine branch... 

Glycosidation3 Glycosidation of the protected actinamine 1 with the pyr-anosyl chloride 2 with AgOTf in CH2C12 proceeds in 60-65% yield. The usual catalyst, silver carbonate, affords less than a 10% yield. 

Spectinomycin (see Scheme 19) has a tricyclic structure, and contains actinamine. In aqueous solution, the carbonyl group is present in hydrated form. 

As the label from D-[6-3H]glucose could not be located in actinamine by the procedure of Scheme 19, Rinehart and coworkers undertook feeding experiments with D-[6-13C]glucose.79 In confirmation of the results of Mitscher and coworkers,77 enrichment in carbon-13 was found at C-6 of actinospectose, and at C-6 of actinamine (see Scheme 20). The label at C-6 of actinamine is similar to the labelling44 of streptidine with D-[6-13C]glucose (see Scheme 13). 

The spectinomycins (O Fig. 20) have a fused three-ring system which consists of a 4,5-disub-stituted actinamine and an ulose. Spectinomycin is produced by Streptomyces spectabilis and Streptomyces flavopersius. It has been clinically used for treatment of the gonorrhea infection. A related structure has been discovered with spenolimycin which was isolated from the culture filtrate of Streptomyces gilvospiralis. Efforts have been directed toward semisynthetic aminoglycoside antibiotics to treat multi-drug resistant bacteria [94]. 

The remaining six carbon atoms of the actinospectacin molecule are accounted for by the sugar moiety, which has been named actinospectose. Two reports have appeared concerning the structure of this sugar and the manner in which it is linked with actinamine. Tarbell and coworkers " examined the products obtained by treating actinospectacin with alkali... 

Davies and coworkers found that streptomycin adenylyl transferase also adenylylates spectinomycin and actinamine. Because of the stereochemical resemblance between actinamine and the o threo methyl-amino alcohol moiety in streptomycin, the site of adenylylation was considered to be that shown by the arrow in formula 15. 

Biochemical and genetic studies by D. H. Smith and coworkers indicated that adenylylation of streptomycin, dihydrostreptomycin, bluensomycin, actinamine, spectinomycin, and dihydrospectinomycin is catalyzed by a single enzyme. 

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