Chemo-Enzymatic Method for the Synthesis of Statine, Phenylstatine and Analogues

• Published in: Advanced synthesis & catalysis Vol. 345; no. 6-7; pp. 699 - 705
• Main Authors: Kambourakis, Spiros, Rozzell, J. David
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.06.2003; WILEY‐VCH Verlag; Wiley
• Subjects: biotechnology; Chemistry; Chemistry, Applied; Chemistry, Organic; dehydrogenase; enzyme; phenylstatine; Physical Sciences; Science & Technology; statine; enzyme; statine; PATHWAYS; biotechnology; ANTI-HIV; dehydrogenase; STEREOSELECTIVE SYNTHESIS; CYCLIC DEPSIPEPTIDE; phenylstatine; ISOSTATINE; PEPSTATIN; EVOLUTION; AMINO-ACIDS; HAPALOSIN; ACID HALF ESTERS
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.200303048

A chemo‐enzymatic method for the synthesis of statine [(3S,4R)‐4‐amino‐3‐hydroxy‐6‐methylheptanoic acid] and statine analogues with natural and unnatural side chains is described. The key step of the synthesis is the diastereoselective reduction of a 2‐alkyl‐substituted 3‐ketoglutarate by an NADPH‐dependent ketoreductase. Two chiral centers are generated in one step, and high yields of a single stereoisomer are obtained (80–90% yield, 90–99% de). Subsequent chemical or enzymatic regio‐selective hydrolysis to the mono‐acid followed by rearrangement under Curtius or Hofmann conditions generates the final statines.