Method for synthesis of rhizoferrin being useful as heavy metal chelators, specifically iron overload diseases such as thalassemia

摘要

A method for synthesizing a compound of the Formula (I), applicable to the preparation of compounds embodying a citric acid moiety of particular enantiometric configuration coupled via an amide linkage to an amine. The preferred embodiment describes the synthesis of rhizoferrin. Wherein: C* is a chiral carbon atom; a and b may be the same or different and are integers from 0 to 10, inclusive; and R is H, alkyl, arylalkyl, carboxyl or Formula (Ia) wherein C* and b have the meanings ascribed above, comprising: (1) Acylating a polyamine of the Formula (II): wherein: a, b and R have the meanings ascribed above, and Q is an amine protective group, with a diester of citric acid having the Formula (III): wherein: R' is alkyl, aryl, aralkyl or cycloalkyl having up to 10 carbon atoms, to produce an amide having the Formula (IV) (2) Hydrolyzing amide (IV) to produce an acid having the formula (V) (3) Deprotecting acid (V) to remove the Q groups, thereby producing an acid of formula (I).