Sulfonate protecting groups. Regioselective sulfonylation of myo-inositol orthoesters-improved synthesis of precursors of D- and L-myo-inositol 1,3,4,5-tetrakisphosphate, myo-inositol 1,3,4,5,6-pentakisphosphate and related derivatives.
The regioselectivity of sulfonylation of myo-inositol orthoesters was controlled by the use of different bases to obtain the desired sulfonate. Monosulfonylation of myo-inositol orthoesters in the presence of one equivalent of sodium hydride or triethylamine resulted in the sulfonylation of the 4-hydroxyl group. The use of pyridine as a base for the same reaction resulted in sulfonylation of the 2-hydroxyl group. Disulfonylation of these orthoesters in the presence of excess sodium hydride yielded the 4,6-di-O-sulfonylated orthoesters. However, the use of triethylamine or pyridine instead of sodium hydride yielded the 2,4-di-O-sulfonylated orthoester. Sulfonylated derivatives of myo-inositol orthoesters were stable to conditions of O-alkylation but were cleaved using magnesium/methanol or sodium methoxide in methanol to regenerate the corresponding myo-inositol orthoester derivative. These new methods of protection-deprotection have been used: (i) for the efficient synthesis of enantiomers of 2,4-di-O-benzyl-myo-inositol, which are precursors for the synthesis of D- and L-myo-inositol 1,3,4,5-tetrakisphosphate; (ii) for the preparation of 2-O-benzyl-myo-inositol which is a precursor for the preparation of myo-inositol 1,3,4,5,6-pentakisphosphate.
Sureshan
Kana M
KM
Division of Organic Synthesis, National Chemical Laboratory, Pune 411 008, India.
Shashidhar
Mysore S
MS
Praveen
Thoniyot
T
Gonnade
Rajesh G
RG
Bhadbhade
Mohan M
MM
D018360:Crystallography, X-Ray; D005021:Ethylamines; D007295:Inositol Phosphates / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011725:Pyridines; D013451:Sulfonic Acids / Q000737:chemistry*
D005021:Ethylamines; D007295:Inositol Phosphates; D011725:Pyridines; D013451:Sulfonic Acids; C451920:inositol-1,3,4,5,6-pentakisphosphate; C081655:inositol-1,3,4,5-tetrakisphosphate; C023666:pyridine; C016162:triethylamine