L-DOPA (I) was esterified by means of MeOH and SOCl2, and the resulting aminoester (II) was protected with benzyloxycarbonyloxy succinimide to give carbamate (III). Further reaction of (III) with 1,2-dibromoethane produced the cyclic diether derivative (IV). Chlorsulfonylation of (IV), followed by basic treatment with DMAP and Et3N gave rise to the benzothiazine (V). After N-alkylation of (V) with iodoethane and K2CO3, basic hydrolysis of the resulting methyl ester (VI) provided carboxylic acid (VII). This was coupled to L-phenylalaninol (VIII) using benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and 1-hydroxybenzotriazole (HOBt) to afford the corresponding amide as a diastereomeric mixture, which was separated by flash chromatography. The required (S,S)-diastereoisomer (IX) was then oxidized to the title aldehyde using Dess-Martin periodinane reagent.

L-DOPA (I) was esterified by means of MeOH and SOCl2, and the resulting aminoester (II) was protected with benzyloxycarbonyloxy succinimide to give carbamate (III). Further reaction of (III) with 1,2-dibromoethane produced the cyclic diether derivative (IV). Chlorsulfonylation of (IV), followed by basic treatment with DMAP and Et3N gave rise to the benzothiazine (V). After N-alkylation of (V) with iodoethane and K2CO3, basic hydrolysis of the resulting methyl ester (VI) provided carboxylic acid (VII). This was coupled to L-phenylalaninol (VIII) using benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and 1-hydroxybenzotriazole (HOBt) to afford the corresponding amide as a diastereomeric mixture, which was separated by flash chromatography. The required (S,S)-diastereoisomer (IX) was then oxidized to the title aldehyde using Dess-Martin periodinane reagent.