239080-22-9Relevant academic research and scientific papers
Intracellular Ca2+-mobilizing adenine nucleotides. Synthesis and biological activity of cyclic ADP-carbocyclic-ribose and C-glycosidic analog of adenophostin A
Shuto,Fukuoka,Abe,Matsuda
, p. 461 - 470 (2007/10/03)
We designed novel Ca2+-mobilizing purine nucleotides, cyclic ADP-carbocyclicribose 4, and its inosine congener 5, and C-glycosidic adenophostin A 6. In the synthesis of cADPR analogs, the intramolecular condensation to form the pyrophosphate linkage should be the key step. We developed an efficient method for forming such an intramolecular pyrophosphate linkage by the activation of the phenylthiophosphate group with I2 or AgNO3. Using this method, we achieved to synthesize the target compounds 4 and 5. The synthesis of C-glycosidic analog 6 of adenophostin A was achieved using a temporary silicon-tethered radical coupling reaction for constructing (3′α, 1″α)-C-glycosidic structure as the key step.
An efficient synthesis of cyclic IDP- and cyclic 8-bromo-IDP-carbocyclic-riboses using a modified hata condensation method to form an intramolecular pyrophosphate linkage as a key step. An entry to a general method for the chemical synthesis of cyclic ADP-ribose analogues
Fukuoka, Masayoshi,Shuto, Satoshi,Minakawa, Noriaki,Ueno, Yoshihito,Matsuda, Akira
, p. 5238 - 5248 (2007/10/03)
An efficient synthesis of cyclic IDP-carbocyclic-ribose (3) and its 8-bromo derivative 6, as stable mimics of cyclic ADP-ribose, was achieved, and a condensation reaction with phenylthiophosphate type substrate 15 or 16 to form an intramolecular pyrophosphate linkage was a key step. N-1-Carbocyclic-ribosylinosine derivative 28 and the corresponding 8-bromo congener 24 were prepared via condensation between N-1-(2,4-dinitrophenyl)inosine derivative 17 and a known optically active carbocyclic amine 18. Compounds 24 and 28 were then converted to the corresponding 5'-phosphoryl-5'-phenylthiophosphate derivatives 15 and 16, respectively, which were substrates for the condensation reaction to form an intramolecular pyrophosphate linkage. Treatment of 8-bromo substrate 15 with I2 or AgNO3 in the presence of molecular sieves 3A (MS 3A) in pyridine at room temperature gave the desired cyclic product 12 quantitatively, while the yield was quite low without MS. The similar reaction of 8-unsubstituted substrate 16 gave the corresponding cyclized product 32 in 81% yield. Acidic treatment of these cyclic pyrophosphates 12 and 32 readily gave the targets 6 and 3, respectively. This result suggests that the construction of N-1-substituted hypoxanthine nucleoside structures from N-1-(2,4-dinitrophenyl)inosine derivatives and the intramolecular condensation by activation of the phenylthiophosphate group with I2 or AgNO3/MS 3A combine to provide a very efficient route for the synthesis of analogues of cyclic ADP-ribose such as 3 and 6. Thus, this may be an entry to a general method for synthesizing biologically important cyclic nucleotides of this type.
Alternative synthesis of cyclic IDP-carbocyclic ribose. Efficient cyclization of an 8-bromo-N1-[5-(phosphoryl)carbocyclic-ribosyl]inosine 5'- phenylthiophosphate derivative mediated by iodine
Fukuoka, Masayoshi,Shuto, Satoshi,Minakawa, Noriaki,Ueno, Yoshihito,Matsuda, Akira
, p. 5361 - 5364 (2007/10/03)
An efficient synthesis of cyclic IDP-carbocyclic-ribose, as a stable mimic for cyclic ADP-ribose, was achieved. N1-Carbocyclic-ribosylinosine derivative 15, prepared from N1(2,4-dinitrophenyl)inosine derivative 10 and an optically active carbocyclic amine 11, was converted to 8-bromo-N1- carbocyclic-ribosylinosine bis-phosphate derivative 20. Treatment of 20 with I2 in the presence of molecular sieves in pyridine gave the desired cyclic product 8 quantitatively, which was deprotected and reductively debrominated to give the target cyclic IDP-carbocyclic ribose (3).
