Synthesis of Protected (2 R ,3 S )-3-Hydroxy-2,4-Diaminobutanoic Acid via a Diastereoselective Henry Reaction on Fmoc-Protected Garner’s Aldehyde

Abstract 3-Hydroxy-2,4-diaminobutanoic acid (HODab) is a nonproteinogenic amino acid found in several cyclic peptide antibiotics. An efficient synthesis of the threo-HODab isomer suitably protected for Fmoc solid-phase peptide synthesis (SPPS) has never been developed. Here, we report an efficient synthesis of protected (2R,3S)-3-hydroxy-2,4-diaminobutanoic acid (Fmoc-D-threo-HODab(TBS,Boc)-OH) that employs a diastereoselective Henry reaction between the Fmoc-protected Garner’s aldehyde and nitromethane as the key step.