Siderophore-Mediated Iron Acquisition: Target for the Development of Selective Antibiotics Towards Mycobacterium tuberculosis - Iron Acquisition by the Genus Mycobacterium - page 72

Fig. 5.8 Generalized mycobactin structructure ( 27 ), catechol-containing analogs [ 59 ]
Fig. 5.9 Modification on the component “C” of the mycobactin structure [ 58 ]
Changes of the linear lysine hydroxamate component “C” also were not tol-
erated. Thus, shortening the side chain of 23 to an acetyl as in mycobactin S2
resulted in loss of inhibitory activity against M. tuberculosis . Replacement of the
linear ε - N -hydroxy lysine with an α -amino adipate allowed syntheses of a series of
analogs 33 - 35 (Fig. 5.9 ) with variation of lipophilicity and iron binding capabili-
ties. Not surprisingly, none of these compounds displayed anti-TB activity.
Since all of the components A-F and related fragment-analogs of the general-
ized mycobactin structure 27 were synthetically available, a number of “truncated”
mycobactins were also synthesized (Fig. 5.10 ), tested and found to be inactive
against M. tuberculosis [ 58 ].
In the development of a platform for the convergent manipulation of mycobac-
tin templates that retained the core structure of the natural mycobactins, Juárez-
Hernández et al., reported the syntheses of mycobactin analogs 47 - 49 (Fig. 5.11 )