Synthesis of adenophostin A

doi:10.1016/S0957-4166(99)00491-7

Tetrahedron: Asymmetry

Volume 11, Issue 2, 11 February 2000, Pages 397-403

https://doi.org/10.1016/S0957-4166(99)00491-7 Get rights and content

Abstract

The natural product and potent agonist of the d-myo-inositol 1,4,5-trisphosphate receptor, adenophostin A, was synthesised from adenosine and d-glucose using efficient methodology. The synthetic material was equipotent with naturally occurring adenophostin A in evoking Ca²⁺ release from the intracellular stores of permeabilised cells.

Section snippets

Acknowledgements

We thank the Wellcome Trust for a Prize Studentship (RDM) and Programme Grant Support (045491 to BVLP and 039662 to CWT), and the BBSRC (CWT). We also thank Dr. M. Takahashi for a sample of authentic natural adenophostin A, Drs. A. M. Riley, D. J. Jenkins and Professor S. Shuto for useful discussions and Dr. A. M. Riley for molecular modelling.

References (24)

Berridge, M. J. Nature (London) 1993, 361,...
Potter, B. V. L.; Lampe, D. Angew. Chem., Int. Ed. Engl. 1995, 34,...
(a) Takahashi, M.; Kagasaki, T.; Hosoya, T.; Takahashi, S. J. Antibiot. 1993, 46, 1643–1647. (b) Takahashi, S.;...
(a) Takahashi, M.; Tanzawa, K.; Takahashi, S. J. Biol. Chem. 1994, 269, 369–372; (b) Hirota, J.; Michikawa, T.;...
Marchant, J. S.; Beecroft, M. D.; Riley, A. M.; Jenkins, D. J.; Marwood, R. D.; Taylor, C. W.; Potter, B. V. L....
(a) Marchant, J. S.; Parker, I. Biochem. J. 1998, 334, 505–509; (b) Hartzell, H. C.; Machaca, K.; Hirayama, Y. Mol....
Jenkins, D. J.; Potter, B. V. L. Carbohydr. Res. 1996, 287,...
Wilcox, R. A.; Erneux, C.; Primrose, W. U.; Gigg, R.; Nahorski, S. R. Mol. Pharmacol. 1995, 47,...
Moitessier, N.; Christian, A. L.; Chapleur, Y.; Humeau, C. Tetrahedron Lett. 1995, 46,...
Murphy, C. T.; Riley, A. M.; Lindley, C. J.; Jenkins, D. J.; Westwick, J.; Potter, B. V. L. Mol. Pharmacol. 1997, 52,...

Jenkins, D. J.; Marwood, R. D.; Potter, B. V. L. Chem. Commun. 1997,...

(a) Shuto, S.; Tatani, K.; Ueno, Y.; Matsuda, A. J. Org. Chem. 1998, 63, 8815–8824; (b) Marwood, R. D.; Riley, A. M.;...

Cited by (30)

The phosphate ester group in secondary metabolites
2022, Natural Product Reports
Covering: 2000 to mid-2021
The phosphate ester is a versatile, widespread functional group involved in a plethora of biological activities. Its presence in secondary metabolites, however, is relatively rare compared to other functionalities and thus is part of a rather unexplored chemical space. Herein, the chemistry of secondary metabolites containing the phosphate ester group is discussed. The text emphasizes their structural diversity, biological and pharmacological profiles, and synthetic approaches employed in the phosphorylation step during total synthesis campaigns, covering the literature from 2000 to mid-2021.
Reliable measurement of free Ca<sup>2+</sup> concentrations in the ER lumen using Mag-Fluo-4
2020, Cell Calcium
Citation Excerpt :
D-myo-inositol 1,4,5- trisphosphate (IP3) was from Enzo (Exeter, UK). Synthetic adenophostin A [24] was a generous gift from Prof Barry V. L. Potter, University of Oxford. Mag-Fluo-4 AM, Mag-Fluo-4 tetrapotassium salt, rabbit Fluorescein/Oregon Green polyclonal antibody (QAb, catalogue number A-889), water-soluble probenecid, RPMI medium and Dulbecco's modified Eagle’s medium/nutrient mixture F-12 with GlutaMAX (DMEM/F-12 GlutaMAX) were from ThermoFisher Scientific (Paisley, UK).
Synthetic Ca²⁺ indicators are widely used to report changes in free [Ca²⁺], usually in the cytosol but also within organelles. Mag-Fluo-4, loaded into the endoplasmic reticulum (ER) by incubating cells with Mag-Fluo-4 AM, has been used to measure changes in free [Ca²⁺] within the ER, where the free [Ca²⁺] is estimated to be between 100 μM and 1 mM. Many results are consistent with Mag-Fluo-4 reliably reporting changes in free [Ca²⁺] within the ER, but the results are difficult to reconcile with the affinity of Mag-Fluo-4 for Ca²⁺ measured in vitro (K_D^Ca ∼22 μM). Using an antibody to quench the fluorescence of indicator that leaked from the ER, we established that the affinity of Mag-Fluo-4 within the ER is much lower (K_D^Ca ∼1 mM) than that measured in vitro. We show that partially de-esterified Mag-Fluo-4 has reduced affinity for Ca²⁺, suggesting that incomplete de-esterification of Mag-Fluo-4 AM within the ER provides indicators with affinities for Ca²⁺ that are both appropriate for the ER lumen and capable of reporting a wide range of free [Ca²⁺].
Recent application of acidic 1,3-azolium salts as promoters in the solution-phase synthesis of nucleosides and nucleotides
2018, Tetrahedron Letters
Citation Excerpt :
The result suggested the existence of an internal hydrogen-bonding structure between the oxygen atom of the P = O and one of the hydrogen atoms of the amino group in the guanine base. IMT was uniquely employed for phosphitylations of three secondary hydroxy groups of the adenine-unprotected intermediate 8 derived from adenosine and glucose (Scheme 3).24 Subsequent oxidation with m-CPBA followed by hydrogenolysis of the benzyl groups afforded adenophostin A, a potent D-myo-inositol 1,4,5-triphosphate receptor-agonist discovered from a culture broth of Penicillium brevicompactum.25,26
Acidic 1,3-azolium salts are prepared from Brønsted acids and 1,3-azoles such as imidazole, thiazole, and oxazole. Acidic imidazolium salts are frequently employed as promoters for the synthesis of nucleotides using the phosphoramidite method in a solution phase. Recently, it was revealed that thiazolium and oxazolium salts catalyzed Vorbrüggen-type N-glycosylation reactions to give nucleosides. These reactivities are attributed to the stronger Brønsted acidities of the thiazolium and oxazolium salts relative to those of the imidazolium salts. This digest focuses on recent progress in the applicability of acidic 1,3-azolium salts as promoters in the solution-phase synthesis of nucleosides and nucleotides.
Joined use of oxazolidinone and desymmetric amino protection: a new strategy for protection of glucosamine
2010, Tetrahedron Letters
Design and synthesis of indole derivatives of adenophostin A. A entry into subtype-selective IP<inf>3</inf> receptor ligands
2010, Tetrahedron Letters
Adenophostins: High-affinity agonists of IP <inf>3</inf> receptors
2010, Current Topics in Membranes
Citation Excerpt :
Many different conformations of adenophostin are therefore possible and the receptor-bound conformation is difficult to predict. Molecular modeling suggests that adenophostin can adopt extended conformations in which the adenosine holds the 2′-phosphate close to the glucose ring in a position similar to that occupied by the 1-phosphate of IP3 (Fig. 1B; Hotoda et al., 1999; Marwood, Correa, Taylor, & Potter, 2000). NMR studies of adenophostin in solution also support some aspects of this type of model (Felemez, Marwood, Potter, & Spiess, 1999; Hotoda et al., 1999).
Adenophostins are naturally occurring high-afﬁnity agonists of inositol 1,4,5-trisphosphate receptors (IP₃R). The three components of adenophostin—bisphosphorylated glucose, phosphorylated ribose, and adenine—are connected by potentially flexible linkages, and the central five-membered ribose ring is also intrinsically more flexible than a six-membered ring such as inositol or glucose. Many different conformations of adenophostin are therefore possible and the receptor-bound conformation is difficult to predict. Molecular modeling suggests that adenophostin can adopt extended conformations in which the adenosine holds the 20-phosphate close to the glucose ring in a position similar to that occupied by the 1-phosphate of IP_3. Activation of an IP₃R begins with IP₃ binding to the IP₃-binding core (IBC). The two domains of the IBC—α and β—form a clam-like structure, the inside of which includes many basic residues that coordinate the phosphate groups of IP₃. Extensive analyses suggest that IP₃R behave similarly whether activated by IP₃ or adenophostin; however the latter typically binds with ∼10-fold greater affinity to all IP₃R subtypes.

View all citing articles on Scopus

View full text