Synthesis of a New N1-Pentyl Analogue of Cyclic Inosine Diphosphate Ribose (cIDPR) as a Stable Potential Mimic of Cyclic ADP Ribose (cADPR)

Galeone, Aldo; Mayol, Luciano; Oliviero, Giorgia; Piccialli, Gennaro; Varra, Michela

doi:10.1002/1099-0690(200212)2002:24<4234::aid-ejoc4234>3.0.co;2-8

Cited by 22 publications

(21 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By employing a similar synthetic strategy, the same group also synthesized the IDPcR analog 100, the "northern" ribose of which was replaced with a pentyl group (Scheme 23) [44]. The key intramolecular condensation occurred effectively using the I 2 /MS3A-promoted method with the phenylthiophosphate substrate 114.…”

Section: Cidpr Analogsmentioning

confidence: 99%

“…In recent years, on the other hand, methods for the chemical synthesis of cADPR analogs have been extensively studied, and useful cADPR analogs, which could not be prepared by the enzymatic and chemo-enzymatic methods, have been synthesized [10,[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46]. In this review, we will mainly focus on these chemical synthetic studies of cADPR analogs.…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Chemistry of Cyclic ADP-Ribose and its Analogs

Shuto¹,

Matsuda

2004

CMC

View full text Add to dashboard Cite

Cyclic ADP-ribose (cADPR), a general mediator involved in Ca2+ signaling, has the characteristic 18-membered ring consisting of an adenine, two riboses and a pyrophosphate, in which the two primary hydroxyl groups of the riboses are linked by a pyrophosphate unit. This review focuses on the chemical synthetic studies of cADPR analogs. These analogs have been used quite effectively in proving the mechanism of cADPR-mediated Ca2+ signaling pathways. These analogs are also expected to be lead structures for the development of drugs. Although cADPR analogs can be synthesized by enzymatic and chemo-enzymatic methods using ADP-ribosyl cyclase, the analogs obtained by these methods are limited due to the substrate-specificity of the enzymes. Consequently, chemical synthetic methods providing a greater variety of cADPR analogs are required. Chemical synthetic studies have demonstrated that the construction of the large 18-membered ring structure is quite difficult. Another problem encountered in the synthesis is the construction of the N1-substituted purine nucleoside structure. The N1-substituted inosine derivatives were prepared by condensation between the N1-(2,4-dinitrophenyl)inosine derivatives and the appropriate amines. For the preparation of the N1-substituted adenosine structures, condensation of the 4-cyano-5-(alkoxymethyleneamino)imidazole nucleosides with the appropriate amines was found to be effective. The first chemical construction of the 18-membered ring was achieved using a bisphosphate-type substrate conformationally restricted in the cyclized product-like syn-form around the N9-glycosyl linkage; however, the yield was inadequate. The key 18-membereding construction was significantly improved by employing the phenylthiophosphate-type substrates. When the substrates were activated by AgNO3 or I2 in the presence of molecular sieves in pyridine, the corresponding 18-membered ring products were obtained in high yields. Using this method as the key step, the chemically and biologically stable cADPR mimic, cADP-carbocyclic-ribose (cADPcR), was synthesized. This method has been applied subsequently to the synthesis of various cADPR analogs.

show abstract

Section: Cidpr Analogsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Chemistry of Cyclic ADP-Ribose and its Analogs

Shuto¹,

Matsuda

2004

CMC

View full text Add to dashboard Cite

show abstract

“…In the carbon-13 labeled case, commercially available 1 was subjected to adenosine deaminase enzyme to cleanly form [ 13 C 5 -ribose] inosine 2. 19 The protected inosine base 3 was arylated on N-1 of the hypoxanthene ring with 2,4-dinitrochlorobenzene by the reported method to afford the derivative 4 in 67% yield after chromatographic purification. 16 The resulting inosine acetonide 2′ (not shown) was chromatographed to obtain 2′ free of buffer salts and enzyme in 69% yield over two steps.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of ¹³C‐labeled 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐[¹³C₅] ribofuranosyl 5′‐monophosphate

Zarkin

Elkins

Gilbert

et al. 2018

Labelled Comp Radiopharmac

View full text Add to dashboard Cite

5-Aminoimidazole-4-carboxamide-1-β-D-[ C ] ribofuranosyl 5'-monophosphate ([ C ribose] AICAR-PO H ) (6) has been synthesized from [ C ]adenosine. Incorporation of the mass-label into [ C ribose] AICAR-PO H provides a useful standard to aid in metabolite identification and quantification in monitoring metabolic pathways. A synthetic route to the C-labeled compound has not been previously reported. Our method employs a hybrid enzymatic, and chemical synthesis approach that applies an enzymatic conversion from adenosine to inosine followed by a ring-cleavage of the protected inosine. A direct phosphorylation of the resulting 2',3'-isopropylidine acadesine (5) was developed to yield the title compound in 99% purity following ion exchange chromatography.

show abstract

“…Subsequently, we focused on the cyclization step. In the first attempts, 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide hydrochloride (EDC) [32] and 1,3 - dicyclohexylcarbodiimide (DCC) [33,34,35], which have been successfully used in previous instances for the pyrophosphate bond formation, were employed. Disappointingly, in our case both these reagents only gave a complex mixture of products (HPLC profiles) among which no cyclization product could be detected by NMR and mass spectral analyses.…”

Section: Resultsmentioning

confidence: 99%

Solid-Phase Synthesis of a New Diphosphate 5-Aminoimidazole-4-carboxamide Riboside (AICAR) Derivative and Studies toward Cyclic AICAR Diphosphate Ribose

et al. 2011

Self Cite

View full text Add to dashboard Cite

The solid-phase synthesis of the first example of a new diphosphate AICAR derivative is reported. The new substance is characterized by the presence of a 5'-phosphate group while a second phosphate moiety is installed on a 5-hydroxypentyl chain attached to the 4-N-position of AICAR. Cyclization of the diphosphate derivative by pyrophosphate bond formation allowed for the formation of a novel AICAR-based cyclic ADP-ribose (cADPR) mimic.

show abstract

Synthesis of a New N1-Pentyl Analogue of Cyclic Inosine Diphosphate Ribose (cIDPR) as a Stable Potential Mimic of Cyclic ADP Ribose (cADPR)

Cited by 22 publications

References 9 publications

Chemistry of Cyclic ADP-Ribose and its Analogs

Chemistry of Cyclic ADP-Ribose and its Analogs

Synthesis of ¹³C‐labeled 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐[¹³C₅] ribofuranosyl 5′‐monophosphate

Solid-Phase Synthesis of a New Diphosphate 5-Aminoimidazole-4-carboxamide Riboside (AICAR) Derivative and Studies toward Cyclic AICAR Diphosphate Ribose

Contact Info

Product

Resources

About

Synthesis of a New N1-Pentyl Analogue of Cyclic Inosine Diphosphate Ribose (cIDPR) as a Stable Potential Mimic of Cyclic ADP Ribose (cADPR)

Cited by 22 publications

References 9 publications

Chemistry of Cyclic ADP-Ribose and its Analogs

Chemistry of Cyclic ADP-Ribose and its Analogs

Synthesis of 13C‐labeled 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐[13C5] ribofuranosyl 5′‐monophosphate

Solid-Phase Synthesis of a New Diphosphate 5-Aminoimidazole-4-carboxamide Riboside (AICAR) Derivative and Studies toward Cyclic AICAR Diphosphate Ribose

Contact Info

Product

Resources

About

Synthesis of ¹³C‐labeled 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐[¹³C₅] ribofuranosyl 5′‐monophosphate