A new approach to the synthesis of l-3-hydroxy-4-methoxy-5-methyl-phenylalanine derivatives from l-tyrosine

A practical procedure to regioselectively install a methyl group and a phenolic hydroxyl group onto l-tyrosine was developed. By using this approach, protected l-3-hydroxy-4-methoxy-5-methyl-phenylalanine and l-3-hydroxy-4-methoxy-5-methyl-phenylalanol, which are utilized in efficient syntheses of the relevant tetrahydroisoquinoline alkaloids, were prepared conveniently with high yield.

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l-N-Benzyloxycarbonyl-3-methyl-4-methoxy-phenylalanine methyl esterC20H23NO5[α]D26=+49 (c 0.99, CHCl3)Source of chirality: l-tyrosineAbsolute configuration: (S)

l-N-Benzyloxycarbonyl-3-formyl-4-methoxy-5-methyl-phenylalanine methyl esterC21H23NO6[α]D27=+63 (c 1.1, CHCl3)Source of chirality: l-tyrosineAbsolute configuration: (S)

l-N-Benzyloxycarbonyl-3-hydroxy-4-methoxy-5-methyl-phenylalanolC19H23NO5[α]D27=-23 (c 1.1, CHCl3)Source of chirality: l-tyrosineAbsolute configuration: (S)

l-N-Benzyloxycarbonyl-3-hydroxy-4-methoxy-5-methyl-phenylalanineC19H21NO6[α]D27=+41 (c 1.1, CHCl3)Source of chirality: l-tyrosineAbsolute configuration: (S)

l-3-Hydroxy-4-methoxy-5-methyl-phenylalanolC11H17NO3[α]D27=-17 (c 0.99, CHCl3)Source of chirality: l-tyrosineAbsolute configuration: (S)