An Efficient and Enantioselective Synthesis of Suitably Protected β‐[1‐(4‐Malonyl)naphthyl]‐L‐alanine and β‐[1‐(4‐Malonylmethyl)naphthyl]‐L‐alanine: Novel Fluorescent and Non‐Hydrolysable Phosphotyrosine Mimetics

Abstract

AbstractMolecular dynamics simulations based on the structure of the Grb7 SH2 domain in complex with the ErbB2 phosphorylated peptide pTyr1139 have suggested that β‐[1‐(4‐malonyl)naphthyl]‐L‐alanine (L‐mNal) may be accommodated in the pTyr binding pocket and offer additional beneficial interactions. Therefore, this compound and its analog β‐[1‐(4‐malonylmethyl)naphthyl]‐L‐alanine (L‐mmNal), which are newnon‐hydrolysable phosphotyrosine mimetics, have been prepared by the catalytic asymmetric hydrogenation of the corresponding prochiral enamides with excellent enantioselectivities. These compounds and their dehydro derivatives show interesting fluorescent properties. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)