Method for preparing 4-hydroxyisoleucine diastereoisomers and enantiomers and derivatives thereof

Diastereoisomers and enantiomers of 4-hydroxyisoleucine and its derivatives (I) are prepared by reducing an isoxazole derivative (II) to (a) produce (I) directly or (b) form a lactone (III), as racemate or enantiomerically enriched mixture, followed by ring opening under basic conditions in a protic or aprotic solvent, and optionally separation of the form required. Diastereoisomers and enantiomers of 4-hydroxyisoleucine and its derivatives of formula (I) are prepared by reducing an isoxazole derivative of formula (II) to (a) produce (I) directly or (b) form a lactone of formula (III), as racemate or enantiomerically enriched mixture, followed by ring opening under basic conditions in a protic or aprotic solvent, and optionally separation of the form required. R1, R2 = H, Ra, CORa (preferably acetyl), COORa, SO2Ra, or NRaRb; Ra, Rb = 1-12C alkyl, optionally substituted 5-8C mono- or poly-cyclic aryl, or aralkyl; R3 = H or Ra; and R4 = Ra. Independent claims are also included for: (1) preparation of (2S,3R,4S)-4-hydroxyisoleucine (Ia) using the method above; and (2) new compounds of formula (IV), (V), (C1), (C2), (E1) and (E2). Provided that one of R1 and R2 is H and the other is other than H.