186703-40-2Relevant academic research and scientific papers
Synthesis of (+)-(1R,2R,4R,6S)-1,6-epoxy-4-benzyloxycyclohexan-2-ol, a key precursor to inositol monophosphatase inhibitors, from (-)-quinic acid
Schulz, Juergen,Beaton, Martin W.,Gani, David
, p. 943 - 954 (2007/10/03)
A new and efficient route to homochiral (+)-(1R,2R,4R,6S)-1,6-epoxy-4-benzyloxycyclohexan-2-ol and its 2-benzyl ether derivative is described, starting from (-)-quinic acid. The compounds are key intermediates in the solution-phase and solid-phase synthesis of inhibitors for inositol monophosphatase. The pivotal step involves a La3+-induced reversal of the diastereoselectivity for the borohydride reduction of an intermediate cyclohexan-4-one. (1R,2R,4R,6R)-(O6-Propyl)cyclohexane-1,2,4,6-tetraol 1-phosphate, predicted to be a submicromolar competitive inhibitor of inositol monophosphatase, was prepared from the title epoxide in 5 steps in good overall yield. The compound proved to be a competitive inhibitor and displayed the expected potency confirming the stereochemical requirements for inhibition. The O2-benzylated epoxide derivative could be stereospecifically alcoholysed using either BF3·(OEt)2 or Yb(III)(OTf)3 as catalysts without appreciable levels of benzyl ether protecting group cleavage. The preparation of the alcoholysis products (1S,2R,4S,6R)-2,4-bis(benzyloxy)-6-isopropyloxycyclohexanol and (1S,2R,4S,6R)-2,4-bis(benzyloxy)-6-(phenethyloxy)cyclohexanol, and the synthesis and evaluation of the inhibitor (1R,2R,4R,6R,2′S)-6-(1′-hydroxy-3′-phenylpropan-2-yloxy)-2,4-d ihydroxycyclohexyl phosphate and its diastereomer (1R,2R,4R,6R,2′R)-6-(1′-hydroxy-3′-phenylpropan-2-yloxy)-2,4-d ihydroxycyclohexyl phosphate are described.
Synthesis of (-)-(1R,2R,4R,6S)-1,6-epoxy-4-benzyloxycyclohexan-2-ol, a key precursor to inositol monophosphatase inhibitors, from (-)-quinic acid
Schulz, Juergen,Gani, David
, p. 111 - 114 (2007/10/03)
A new and efficient route to (-)-(1R,2R,4R,6S)-1,6-epoxy-4-benzyloxycyclohexan-2-ol is described starting from (-)-quinic acid. The pivotal step involves a La3+-induced reversal of the diastereoselectivity for the borohydride reduction of an intermediate cyclohexan-4-one. (1R,2R,4R,6R)-6-Propyloxycyclohexan-1,2,4-triol 1-phosphate, predicted to be a submicromolar inhibitor of inositol monophosphatase, was prepared from the epoxide in 20% yield and displayed the expected potency.
