1,5,5-Trimethylhydantoin (I) was alkylated with tert-butyl 4-bromobutyrate (II) in the presence of NaH in DMF to afford (III). The tert-butyl ester group of (III) was then cleaved by treatment with trifluoroacetic acid to yield carboxylic acid (IV). Bromination of (IV) under Hell-Volhard-Zelinskii conditions furnished the alpha-bromoacid (V), which was condensed with potassium thioacetate to give the thioacetate ester (VI). Subsequent EDC-promoted coupling of (VI) with L-leucyl-L-tert-leucine-N-methylamide (VII) provided amide (VIII) as an epimeric mixture. The thioacetate ester of (VIII) was then hydrolyzed by means of methanolic ammonia to give thiol (IX) (1). The title diastereoisomer was finally isolated by using preparative HPLC.

1,5,5-Trimethylhydantoin (I) was alkylated with tert-butyl 4-bromobutyrate (II) in the presence of NaH in DMF to afford (III). The tert-butyl ester group of (III) was then cleaved by treatment with trifluoroacetic acid to yield carboxylic acid (IV). Bromination of (IV) under Hell-Volhard-Zelinskii conditions furnished the alpha-bromoacid (V), which was condensed with potassium thioacetate to give the thioacetate ester (VI). Subsequent EDC-promoted coupling of (VI) with L-leucyl-L-tert-leucine-N-methylamide (VII) provided amide (VIII) as an epimeric mixture. The thioacetate ester of (VIII) was then hydrolyzed by means of methanolic ammonia to give thiol (IX) (1). The title diastereoisomer was finally isolated by using preparative HPLC.