Synthesis of a peptide lactone, N (3 hydroxypicolinyl) threonyl D leucyl prolylsarcosyl leucyl alanyl alanine threonine lactone

The synthesis of a peptide lactone, N-(3-hydroxypicolinyl)-threonyl-D-leucyl-prolylsarcosyl-leucyl-alanyl-alanine Threonine Lactone (21) is described. The t-butoxycarbonyl group of t-butyl O-(t-butoxycarbonyl-alanyl)-N-benzyloxycarbonyl-threonyl-D-leucyl-prolylsarcosinate (12) was deblocked selectively with formic acid in good yield. The coupling of 12 with the azide derived from t-butoxycarbonyl-leucyl-alanine hydrazide (15) with isopentyl nitrite gave a heptapeptide ester 17. Deblocking, cyclization, and hydrogenation gave a heptapeptide lactone 20 which was coupled with 3-hydroxypicolinic acid yielding 21