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
Molecular 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)