Yb(OTf)₃-Catalyzed Desymmetrization of myo-Inositol 1,3,5-Orthoformate and Its Application in the Synthesis of Chiral Inositol Phosphates

Abstract

A variety of inositol phosphates including myo-inositol 1,4,5-trisphosphate, which is a secondary messenger in transmembrane signaling, were selectively synthesized via Yb(OTf)-catalyzed desymmetrization of myo-inositol 1,3,5-orthoformate using a proline-based chiral anhydride as an acylation precursor. The investigated catalytic system could regioselectively differentiate the enantiotopic hydroxy groups of myo-inositol 1,3,5-orthoformate in the presence of a chiral auxiliary. This key step to generate a suitably protected chiral myo-inositol derivatives is described here as a unified approach to access inositol phosphates.

Access to Enantiomeric Organic Compounds with Potential for Synthesis via Racemic Conglomerates: Inositol Derivatives as a Case in Point

“…This agrees with the fact that the known (+)-1D-2,4-di- O -benzyl- myo -inositol ( D14 , Scheme ) was obtained from L6 . The benzyl ether D14 is a precursor for the preparation of 1L- myo -inositol-1,3,4,5-tetrakisphosphate. , Hence, in principle, this constitutes a formal synthesis of the latter enantiomeric tetrakisphosphate, without the aid of any external optically active molecular entity.…”

“…Synthesis of enantiomerically pure organic compounds and resolution of racemates have gained unprecedented significance due to different properties of enantiomers and racemates, e.g ., the therapeutic efficacy of drugs. − Enantiomeric organic compounds can be extracted routinely from natural sources, although with wide variation in inputs in terms of cost, effort, and time. Due to the high enantiomeric purity of organic compounds isolable from natural sources, many of them form the starting materials for the synthesis of natural and unnatural chiral molecular entities. − Most laboratory methods of preparation of enantiomeric compounds involve the use of enantiomeric molecular entities such as catalysts (including enzymes) for asymmetric synthesis, chiral auxiliaries, resolving agents, or chiral stationary phases for the separation of enantiomers (in a racemate). ,− Almost all of these methods to obtain enantiomers depend on the solution-state chemistry. Enantiomers present in a racemate can also be separated by preferential enrichment of enantiomers and by preferential crystallization of conglomerates .…”

Radical polymerizations of two stereoisomeric trimethacrylates with rigid adamantane‐like cores from naturally occurring myo‐inositol

“…Using myo ‐inositol as a starting material for bioactive molecules, a variety of regioselective protection protocols for its hydroxyl groups have been established to enable precise syntheses of targeted myo ‐inositol‐derivatives . These protection protocols typically involve orthoesterification, which is commonly used for the protection of the three hydroxyl groups at the 1‐, 3‐, and 5‐positions to give corresponding triols such as 1 shown in Scheme . Interestingly, 1 has an adamantane‐like core structure, allowing the synthesis of polymers consisting of conformationally constrained repeating units.…”