The preparation of racemic and enantiomerically pure myo-inositol derivatives as intermediates for the synthesis of phosphatidylinositol 3-, 3,4-bis-, and 3,4,5-tris-phosphates and for the synthesis of analogues of 1d-myo-inositol 1,3,4,5-tetrakisphosphate

Desai, Trupti; Gigg, Jill; Gigg, Roy; Martı́n-Zamora, Eloı́sa

doi:10.1016/s0008-6215(96)00211-x

Cited by 11 publications

(10 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Column chromatographies were performed with silca gel 60 (Merck). (10) [28][29][30]44 (800 mg; 1.63 mmol) was dissolved in dried THF (8 mL). The reaction mixture was cooled to 0°C and sodium hydride (5 equiv; 326 mg; 60% dispersion; 8.15 mmol) was added.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, Acid−Base Behavior, and Binding Properties of 6-Modified myo-Inositol 1,4,5-Tris(phosphate)s

et al. 1999

View full text Add to dashboard Cite

myo-Inositol 1,4,5-tris(phosphate) was modified at position 6. The analogues synthesized are reported in this publication are 6-deoxy-myo-inositol 1,4,5-tris(phosphate), 6-fluoro-6-deoxy-myo-inositol 1,4,5-tris(phosphate), epi-inositol 1, 4,5-tris(phosphate), and 6-amino-6-deoxy-myo-inositol 1,4, 5-tris(phosphate). These derivatives showed poor affinity for the Ins(1,4,5)P(3) receptors. The inframolecular acid-base behavior and the cooperative effects between the phosphate groups could help explain the loss of affinity of these 6-modified analogues.

show abstract

Section: Methodsmentioning

confidence: 99%

Synthesis, Acid−Base Behavior, and Binding Properties of 6-Modified myo-Inositol 1,4,5-Tris(phosphate)s

et al. 1999

View full text Add to dashboard Cite

show abstract

“…To establish suitable conditions for the monobenzylation on the desired 31 , we used the myo -inositol derivative racemic 33 as a model for optimizing the tin-mediated reaction (Scheme ). Benzylation of 33 had been previously performed under either strongly basic conditions or via tin-mediated one-pot reaction conditions . We used a two-phase reaction condition, i.e., isolation of the stannylene-ketal intermediate 34 before adding BnBr, to avoid possible benzylation on the purine moiety.…”

Section: Resultsmentioning

confidence: 99%

“…The conditions of 10% TFA in DCM have been successfully employed to remove PMB groups from sugar molecules without affecting the glycosidic linkage . Because of the presence of the sensitive 2,3- O -isopropylidene group, we initially avoided acidic conditions when deprotecting the model molecule 45 (Scheme ). However, the oxidative process using CAN only generated the target compound 33 in low yield, along with the fully hydrolyzed byproduct 47 (Table , entry 1).…”

Section: Resultsmentioning

confidence: 99%

“…Benzylation of 33 had been previously performed under either strongly basic conditions 73 or via tin-mediated one-pot reaction conditions. 74 We used a two-phase reaction condition, i.e., isolation of the stannylene-ketal intermediate 34 before adding BnBr, to avoid possible benzylation on the purine moiety. Initially, the reaction was performed in a mixed solvent of toluene and methanol for both phases (Table 1, entry 1).…”

Section: ■ Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inositol Adenophostin: Convergent Synthesis of a Potent Agonist of d-myo-Inositol 1,4,5-Trisphosphate Receptors

Döhle

Mills

et al. 2020

ACS Omega

View full text Add to dashboard Cite

d-myo-Inositol 1,4,5-trisphosphate receptors (IP3Rs) are Ca2+ channels activated by the intracellular messenger inositol 1,4,5-trisphosphate (IP3, 1). The glyconucleotide adenophostin A (AdA, 2) is a potent agonist of IP3Rs. A recent synthesis of d-chiro-inositol adenophostin (InsAdA, 5) employed suitably protected chiral building blocks and replaced the d-glucose core by d-chiro-inositol. An alternative approach to fully chiral material is now reported using intrinsic sugar chirality to avoid early isomer resolution, involving the coupling of a protected and activated racemic myo-inositol derivative to a d-ribose derivative. Diastereoisomer separation was achieved after trans-isopropylidene group removal and the absolute ribose–inositol conjugate stereochemistry assigned with reference to the earlier synthesis. Optimization of stannylene-mediated regiospecific benzylation was explored using the model 1,2-O-isopropylidene-3,6-di-O-benzyl-myo-inositol and conditions successfully transferred to one conjugate diastereoisomer with 3:1 selectivity. However, only roughly 1:1 regiospecificity was achieved on the required diastereoisomer. The conjugate regioisomers of benzyl derivatives 39 and 40 were successfully separated and 39 was transformed subsequently to InsAdA after amination, pan-phosphorylation, and deprotection. InsAdA from this synthetic route bound with greater affinity than AdA to IP3R1 and was more potent in releasing Ca2+ from intracellular stores through IP3Rs. It is the most potent full agonist of IP3R1 known and .equipotent with material from the fully chiral synthetic route.

show abstract

“…Since an extended exposure to the acid resulted in the concomitant hydrolysis of the cis -1,2-ketal, the reaction was carefully monitored by TLC and was stopped when all the substrate disappeared. Stannylidene-activated alkylation by reacting (+)- 2 with n -Bu 2 SnO, followed by allyl bromide and CsF, selectively introduced an allyl function at the 6-OH over 5-OH, 8a,9a, yielding (−)- 3 . Subsequent 5-O-benzylation and removal of the cis -ketal gave the diol (−)- 5 .…”

Section: Resultsmentioning

confidence: 99%

Molecular Recognition at the Phosphatidylinositol 3,4,5-Trisphosphate-Binding Site. Studies Using the Permuted Isomers of Phosphatidylinositol Trisphosphate

et al. 1998

View full text Add to dashboard Cite

Permuted isomers of L-R-phosphatidyl-D-myo-inositol trisphosphate (PtdInsP 3 ), including PtdIns-(3,4,5)P 3 , PtdIns(3,4,6)P 3 , PtdIns(3,5,6)P 3 , and PtdIns(4,5,6)P 3 , have been synthesized as part of our effort to understand the underlying principles governing ligand selection for PtdIns(3,4,5)P 3 -specific binding proteins. These PtdInsP 3 isomers are examined by using two PtdIns(3,4,5)P 3 -dependent functional assays: binding to the C-terminal SH2 domain of the p85 regulatory subunit of PI 3-kinase and platelet aggregation. Our data show that all these isomers bind to the SH2 domain with comparable affinity despite variation in the regioisomeric distribution of phosphate functions. Moreover, all these phospholipids are capable of triggering platelet aggregation with the relative potency of PtdIns(3,4,5)P 3 > PtdIns(3,5,6)P 3 > PtdIns(4,5,6)P 3 > PtdIns(3,4,6)P 3 . Evidence suggests that these PtdInsP 3 's facilitate cell aggregation by activating Ca 2+ influx across the plasma membrane. In contrast, other inositol lipids examined including PtdIns(3,4)P 2 , PtdIns-(4,5)P 2 , PtdIns(3)P, and PtdIns(4)P are ineffective in eliciting the aggregation even at much higher concentrations. Taken together, the present data suggest that the charge density on the phosphorylated inositol ring represents a key factor in determining the phosphoinositide binding specificity of target proteins. It is conceivable that the interaction with the PtdIns(3,4,5)P 3 -binding motif requires the participation of all three phosphates on the headgroup of PtdIns(3,4,5)P 3 . Consequently, other membrane phosphoinositides (e.g., the bis-and monophosphates) become thermodynamically unfavorable for the binding to these PtdIns(3,4,5)P 3 targets.

show abstract

The preparation of racemic and enantiomerically pure myo-inositol derivatives as intermediates for the synthesis of phosphatidylinositol 3-, 3,4-bis-, and 3,4,5-tris-phosphates and for the synthesis of analogues of 1d-myo-inositol 1,3,4,5-tetrakisphosphate

Cited by 11 publications

References 52 publications

Synthesis, Acid−Base Behavior, and Binding Properties of 6-Modified myo-Inositol 1,4,5-Tris(phosphate)s

Synthesis, Acid−Base Behavior, and Binding Properties of 6-Modified myo-Inositol 1,4,5-Tris(phosphate)s

Inositol Adenophostin: Convergent Synthesis of a Potent Agonist of d-myo-Inositol 1,4,5-Trisphosphate Receptors

Molecular Recognition at the Phosphatidylinositol 3,4,5-Trisphosphate-Binding Site. Studies Using the Permuted Isomers of Phosphatidylinositol Trisphosphate

Contact Info

Product

Resources

About