Synthesis of 3-Boc-(1,3)-oxazinane-protected amino aldehydes from amino acids and their conversion into urea precursors. Novel building blocks for combinatorial synthesis

Starting from the large pool of chiral amino acids a route to protected amino aldehyde building blocks for combinatorial chemistry has been developed. Eight a-amino aldehydes have been synthesized from Cbz- or Fmoc-protected cc-amino acids through partial reduction of Weinreb amides or partial oxidation with Dess-Martin periodinane of amino alcohols. The a-amino aldehydes have been protected as their acid labile 3-Boc-(1,3)oxazinanes using aminopropanol and sodium sulfate followed by treatment with Boc(2)O. Noteworthy, both reduction and protection proceed with minimal epimerization. 3-Boc-(1,3)-oxazinane (Box) protected 2-amino-benzaldehyd have also been synthesized. Efficient precursors for the formation of ureas were prepared from the Box-protected amino aldehydes by forming activated carbamates with bis(pentafluorophenyl) carbonate or forming activated imidazoyl urea with carbonyldiimidazole.