To enhance cell membrane penetration, we employed a prodrug approach to mask the phosphate group of MN551 . At physiological pH a phosphate group of pY residue is doubly negatively charged and to enhance cell permeability, the negative charge can be masked by enzyme-cleavable hydrophobic groups (Figure ) . We decided to make pivaloyloxymethyl (POM) and aryloxy phosphoramidate prodrugs of MN551 as these prodrug technologies have been proven successful for delivering phosphate-containing molecules inside cells, including phosphotyrosine derivatives . Aryloxy phosphoramidate prodrugs of MN551, compounds 21-23, were obtained by treatment of appropriate tyrosine derivative 17 with (chloro(naphthalen-1-yloxy)phosphoryl)-L-alaninates as described by Miccoli et al., followed by Bocdeprotection and acylation with chloroacetyl chloride (Supplementary Scheme 4) . POM modified phosphonate 25 (hence afterward referred to as MN714) was prepared from tyrosine 17 with the use of bis(POM) phosphoryl chloride (Supplementary Scheme 4) .