| Unambiguous total synthesis of the enantiomers of myo-inositol 1,3,4-trisphosphate: 1L-myo-inositol 1,3,4-trisphosphate mobilizes intracellular Ca2+ in Limulus photoreceptors. | |
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MedLine Citation:
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PMID: 7966153 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Syntheses of the enantiomers of myo-inositol 1,3,4-trisphosphate are described. 1,4-Di-O-allyl-myo-inositol was regioselectively p-methoxybenzylated at the 3-position to give 1,4-di-O-allyl-3-O-(p-methoxybenzyl)-myo-inositol followed by benzylation of the remaining free hydroxyl groups to give the key intermediate 1,4-di-O-allyl-2,5,6-tri-O-benzyl-3-O-(p-methoxybenzyl)-myo-inositol. Removal of the p-methoxybenzyl and allyl groups gave 2,4,5-tri-O-benzyl-myo-inositol which was phosphitylated with bis(benzyloxy)(diisopropylamino)phosphine to give the fully protected trisphosphite triester. Oxidation using tert-butyl hydroperoxide gave 2,5,6-tri-O-benzyl-1,3,4-tris(dibenzylphospho)-myo-inositol, and deprotection using sodium in liquid ammonia gave racemic myo-inositol 1,3,4-trisphosphate. Deprotection of the key intermediate 1,4-di-O-allyl-2,5,6-tri-O-benzyl-3-O-(p-methoxybenzyl)-myo-inositol by isomerization of allyl groups followed by mild acid hydrolysis gave 2,4,5-tri-O-benzyl-1-O-(p-methoxybenzyl)-myo-inositol, which was converted to the diastereoisomeric (bis-(-)-camphanates. The diastereoisomers were separated by column chromatography and the camphanates and the p-methoxybenzyl group removed by saponification and acid hydrolysis, respectively, for each diastereoisomer to give the enantiomers of 2,4,5-tri-O-benzyl-myo-inositol. The absolute configurations of the latter were established by conversion of 1L-2,5,6-tri-O-benzyl-3-O-(p-methoxybenyl)-myo-inositol to the known 1L-1,2,4,5,6-penta-O-benzyl-myo-inositol. Phosphorylation and deblocking gave the D- and L-enantiomers of myo-inositol 1,3,4-trisphosphate. Biological evaluation in Limulus photoreceptors showed that 1L-myo-inositol 1,3,4-trisphosphate was much more active than the D-enantiomer, producing repetitive bursts of depolarization due to mobilization of intracellular calcium. |
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Authors:
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A M Riley; R Payne; B V Potter |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 37 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 1994 Nov |
Date Detail:
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Created Date: 1994-12-29 Completed Date: 1994-12-29 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 3918-27 Citation Subset: IM |
Affiliation:
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Department of Medicinal Chemistry, School of Pharmacy and Pharmacology, University of Bath, U.K. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium / metabolism* Horseshoe Crabs Inositol Phosphates / chemical synthesis, metabolism* Photoreceptor Cells, Invertebrate / drug effects*, metabolism Stereoisomerism |
| Chemical | |
Reg. No./Substance:
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0/Inositol Phosphates; 7440-70-2/Calcium; 98102-63-7/inositol 1,3,4-trisphosphate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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