Synthetic Studies On Hydroxamate Siderophore Baumannoferrin B

With the increasing spread of antibiotic resistance in recent years,modern medicine is facing a great challenge.The emergence of multi-drug resistant bacteria such as superbugs is becoming a serious threat to the health and safety of mankind.The bacterial iron carrier siderophores are getting increasing attention due to their unique iron transport function and mechanism.The siderophore based “Trajan Horse”antibacterial discovery has become an important strategy to identify navel antibiotics to treat bacterial infections caused by resistant Gram-positive and Gram-negative bacteria.Baumannoferrin is a novel natural siderophore produced by mutant Acinetobacter baumannii AYE.Acinetobactin,a siderophore produced by Acinetobacter baumannii,plays an important role in the iron acquisition of Acinetobacter baumannii.Mutant Acinetobacter baumannii AYE does not produce Acinetobactin,which is a widely studied catechol siderophore,it instead produces different high affinity hydroxamate siderophores to replace Acinetobactin for iron acquisition,which are Baumannoferrin A and Baumannoferrin B.This finding provides an idea for the potential development of new antibacterial drugs,especially against Acinetobacter baumannii.Since the synthesis of these new hydroxamate siderophores Baumannoferrins has not been reported yet,it is of great significance to study the synthesis of Baumannoferrins.In this thesis research,Baumannoferrin B was studied for its chemical synthesis.Decanoic acid,L-malic acid,and N-carbobenzyloxy-L-glutamine were used as initial starting materials.The advanced intermediate(1)of Baumannoferrin B with a benzyl protective group was synthesized in 9 longest linear steps and 16 combined steps.Future studies shall focus on removing the benzyl protection group from this advanced intermediate(1)to obtain the natural Baumannoferrin B.Our studies laid a foundation for the synthesis of natural Baumannoferrins as well as their potential conjugates with selected antibiotics to discover new antibiotics.