176200-07-0Relevant academic research and scientific papers
Chemoselective alcoholysis/acetolysis of trans-ketals over cis-ketals and its application in the total synthesis of the cellular second messenger, d-myo-inositol-1,4,5-trisphosphate
Vidyasagar, Adiyala,Pathigoolla, Atchutarao,Sureshan, Kana M.
, p. 5443 - 5453 (2013/09/02)
The involvement of natural phosphoinositols in various cellular signalling processes and the use of synthetic inositol derivatives in catalysis, supramolecular chemistry, natural product synthesis etc. gave momentum to myo-inositol chemistry. The presence of six secondary hydroxyl groups necessitates efficient protection-deprotection strategies for the synthesis of inositol derivatives. An important strategy for the initial protection of myo-inositol is the di-ketalization, which gives a mixture of three diketals, each having both cis-fused and trans-fused ketals. It is important to have methodologies either to selectively hydrolyze one of the two ketals or to convert one of the two acid labile ketals to an orthogonal base labile protecting group. By exploiting the difference in strain between trans-ketals and cis-ketals, we developed two operationally simple, high yielding methodologies for the chemoselective hydrolysis/acetolysis of trans-ketals (both isopropylidene and cyclohexylidene) of inositols, leaving the cis-ketal undisturbed, using cheap and easily preparable H2SO 4-silica as the catalyst. Also, terminal ketal moieties of carbohydrates and acyclic polyols could be selectively hydrolyzed/acetolyzed leaving the internal ketals intact. The use of methanol as the solvent leads to chemoselective alcoholysis but the use of DCM and acetic anhydride leads to chemoselective acetolysis. Applying this methodology, a short synthesis of d-myo-inositol-1,4,5-trisphosphate has been achieved. The Royal Society of Chemistry.
Divergent synthesis of all possible optically active regioisomers of myo-inositol mono- and bisphosphates
Seo, Kyung-Chang,Yu, Seok-Ho,Chung, Sung-Kee
, p. 305 - 327 (2008/02/12)
All possible optically active regioisomers of myo-inositol mono- and bisphosphates were synthesized using inositol derivatives suitably protected with various protecting groups (IRns) as key intermediates. A series of procedures including Novozym 435 cata
Syntheses of D- and L-myo-inositol 1,2,4,5-tetrakisphosphate and stereoselectivity of the I(1,4,5)P3 receptor binding.
Chung,Shin,Chang,Suh,Kim
, p. 659 - 662 (2007/10/03)
D- and L-myo-Inositol 1,2,4,5-tetrakisphosphate [D- & L-I(1,2,4,5)P4], which are analogues of D-myo-Inositol 1,4,5-trisphosphate [D-I(1,4,5)P3], a calcium mobilizing second messenger, were synthesized via resolution of the camphanate ester of a myo-inositol derivative, and the binding affinities to I(1,4,5)P3 receptor were measured.
Synthesis of the enantiomers of myo-inositol 1,2,4,5-tetrakisphosphate, a regioisomer of myo-inositol 1,3,4,5-tetrakisphosphate
Mills, Stephen J.,Potter, Barry V. L.
, p. 1279 - 1286 (2007/10/03)
Routes for the synthesis of racemic myo-inositol 1,2,4,5-tetrakisphosphate DL-Ins(1,2,4,5)P4 5ab and the chiral antipodes D- and L-myo-inositol 1,2,4,5-tetrakisphosphate 5a and 5b, respectively, are described. For the synthesis of racemate 5ab, 3,6-di-O-benzoyl-1,2:4,5-di-O-isopropylidene-myo-inositol 7ab is prepared in two steps from myo-inositol. The ketals are hydrolysed under acidic conditions to give DL-1,4-di-O-benzoyl-myo-inositol 8ab. Phosphitylation of compounds 8ab using chloro(diethoxy)-phosphine in the presence of base, followed by oxidation and a three-step deprotection strategy, gives DL-Ins(1,2,4,5)P4 5ab. The chiral tetrakisphosphates 5a and 5b are synthesized using a different route. The 4,5-isopropylidene group of DL-3,6-di-O-benzyl-1,2:4,5-di-O-isopropylidene-myo-inositol 13ab are selectively removed under mild acidic conditions to give diol 14ab. p-Methoxybenzylation at the 4,5-positions followed by acid hydrolysis of the cis-isopropylidene ketal affords cis-diol 16ab. Selective coupling of (S)-(+)-O-acetylmandelic acid with diol 16ab at the equatorial hydroxy group provides two diastereoisomers 18 and 19, which are separated by chromatography. Basic hydrolysis of the individual diastereoisomers provides the enantiomers 16a and 16b. Acidic hydrolysis gives D- and L-3,6-di-O-benzyl-myo-inositol 20a and 20b, respectively. Phosphitylation and oxidation of tetraols 20a and 20b gives the fully blocked derivatives, which are deprotected to give tetrakisphosphates 5a and 5b, respectively. The absolute configuration of compound 20a is established by a chemical method. DL-1,2:4,5-Di-O-isopropylidene-myo-inositol 12ab is coupled to (S)-(+)-O-acetylmandelic acid to give a mixture of bis-esters 26 and 27 and crystallisation of the mixture of diastereoisomers affords pure isomer 27. Basic hydrolysis gives the pure enantiomer 12a (for which the absolute configuration is known) and benzylation followed by acid hydrolysis gives tetraol 20a with the same physical properties as compound 20a prepared by a different route described previously. D-Ins(1,2,4,5)P4 5a is a potent mobiliser of intracellular Ca2+ ions in permeabilised platelets, while L-Ins(1,2,4,5)P4 5b is inactive.
