Total synthesis of rhizoferrin, an iron chelator

Abstract

The absolute configuration of rhizoferrin, a novel siderophore isolated from the fungus Rhizopus microsporus var. rhizopodiformis, was determined via its total synthesis. The principal steps in the synthesis of this naturally occurring iron chelator involve a simple coupling of key intermediate ( R)-1,2-dimethyl citrate with N 1, N 4-dibenzyl-1,4-diaminobutane followed by ester hydrolysis and debenzylation. This is the first example of a total synthesis of a citrate-based siderophore from a chiral citric acid fragment, the structure of which was confirmed by single crystal X-ray diffraction.