Enantiodivergence in small-molecule catalysis of asymmetric phosphorylation: concise total syntheses of the enantiomeric D-myo-inositol-1-phosphate and D-myo-inositol-3-phosphate.
Peptide-based catalysts have been found that catalyze the enantiodivergent phosphorylation of a meso myo-inositol-derived triol (1). The sequential screening of random peptide libraries, followed by the evaluation of a focused library, led to the identification of two peptides (2 and 24) that are complementary in producing enantiomeric D-myo-inositol-1-phosphate and D-myo-inositol-3-phosphate derivatives. The catalysts were then used to complete efficient total syntheses of both D-I-1P and D-I-3P in optically pure form. Additional information is gleaned from relative rate experiments that unambiguously show the catalysts to afford enantioselection through rate accelerative pathways with respect to simple achiral alkylimidazole catalysts. Furthermore, solvent effect studies show that the two enantiodivergent catalysts exhibit different tolerances of polar media. The systematic discovery of site-selective catalysts establishes a basis for future studies of chiral catalysts that differentiate unique functional groups in polyfunctional molecules.
Sculimbrene
Bianca R
BR
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467-3860, USA.
Morgan
Adam J
AJ
Miller
Scott J
SJ
D002384:Catalysis; D007295:Inositol Phosphates / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D009842:Oligopeptides / Q000737:chemistry; D010766:Phosphorylation; D013237:Stereoisomerism
D007295:Inositol Phosphates; D009842:Oligopeptides; C002647:inositol 1-phosphate; C052128:inositol 3-phosphate