A highly efficient stereocontrolled synthesis of (S)-2′,6′-dimethyltyrosine [(S)-DMT]

A new, practical and very convenient stereocontrolled synthesis of (S)-2′,6′-dimethyltyrosine [(S)-Dmt] 4 was accomplished in a good yield, starting from the chiral synthon 1,4-N,N-[(S)-phenylethyl]-piperazine-2,5-dione 1. The procedure, which is an extension of our original strategy and occurs with a high level of stereoselectivity (>98%), is simple and inexpensive allowing us to prepare the unnatural α-aminoacid (S)-Dmt also on a multi-gram scale.

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(3S,6S)-1,4-N,N-[(S)-Phenylethyl]-3,6-bis[4-O-carbethoxy-2,6-dimethyl-benzyl]-piperazine-2,5-dioneC44H50N2O8[α]D = −61.1 (c 0.9, CHCl3)Source of chirality: (S)-phenylethylamineAbsolute configuration: (3S,6S,1’S)

(S)-2′,6′-dimethyltyrosineC11H15NO3[α]D = +72.9 (c 0.5, 0.5M HCl)Source of chirality: (S)-phenylethylamineAbsolute configuration: (2S)