19-08-2014, 12:00 PM
In plants and bacteria unlike mammals lysine is synthesized de novo and is utilized for protein biosynthesis. Crucially, however, most bacteria also require either lysine, or its biosynthetic precursor, meso-diaminopimelic acid (DAP), as a component of the peptidoglycan layer of the cell wall. For these reasons DAP was selected as a target for designing novel antimicrobial chemotherapeutic agents as DAP antimetabolite.
In plants and bacteria unlike mammals lysine is synthesized de novo and is utilized for protein biosynthesis. Crucially, however, most bacteria also require either lysine, or its biosynthetic precursor, meso-diaminopimelic acid (DAP), as a component of the peptidoglycan layer of the cell wall. For these reasons DAP was selected as a target for designing novel antimicrobial chemotherapeutic agents as DAP antimetabolite.
Considering the literature reported highly potent hydrazino-DAP analogues, the DAP orientation within the peptidoglycan crosslinkage, the proposed SAR and the importance of lanthionine as good bioisostere of DAP and as immunostimulant, general structure of novel chemotherapeutic agent in the form of lanthionine derivatives were designed.
Based on this general structure few analogues were decided to be synthesized. General synthetic scheme was designed using retrosynthetic analysis. The syntheses were successfully carried out with this 10 step synthetic scheme, using protection-deprotection strategies. All the synthesized molecules were purified and characterized by IR and 1H NMR spectroscopic methods.
The synthesized lanthionine derivatives were biologically screened for their antimicrobial activities as per pharmacopoeial specifications.