Carbocyclic analogues of d-ribose-5-phosphate: Synthesis and behavior with 5-phosphoribosyl α-1-pyrophosphate synthetases

• Published in: Bioorganic & medicinal chemistry Vol. 4; no. 7; pp. 1077 - 1088
• Main Authors: Parry, Ronald J., Burns, Mark R., Skae, Phillip N., Hoyt, Jeffrey C., Pal, Biman
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.1996
• Subjects: Humans; Hydrogen-Ion Concentration; Kinetics; Pyrimidine Nucleotides - metabolism; Ribose-Phosphate Pyrophosphokinase - metabolism; Ribosemonophosphates - chemical synthesis; Ribosemonophosphates - metabolism; Salmonella typhimurium; Stereoisomerism; DMAP, 4-dimethyl-aminopyridine; CI, chemical ionization; cPRPP, 1α-pyrophosphoryl-2α,3α-dihydroxy-4β-cyclopentanemethanol-5-phosphate; EDTA, ethylenediaminetetraacetic acid; LDH, lactate dehydrogenase; APP-MP, 4-amino-8-(β- d-ribofuranosylamino)-pyrimido [5,4- d]pyrimidine-5′-monophosphate; R5P, d-ribose-5-phosphate; THP, tetrahydropyranyl; LDA, lithium diisopropylamide; ATP, ádenosine-5′-triphosphate; PRPP, 5-phospho- d-ribosyl-1α-pyrophosphate; TMS, tetramethylsilane; ES, electrospray; NADH, nicotinamide adenine dinucleotide; PK pyruvate kinase; DDO, 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone; TSP, sodium 3-(trimethylsilyl)propionate; PEP, phosphoenolpyruvate; AMP, adenosine-5′-monophosphate; AK, adenylate kinase
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/0968-0896(96)00090-9

The synthesis of cyclopentyl and cyclopentenyl analogues of the α-anomer of d-ribose-5-phosphate from d-ribonolactone and d-ribose is described. These analogues, which have the same absolute configuration as d-ribose-5-phosphate, were incubated with PRPP synthetases in an attempt to prepare the corresponding carbocyclic PRPP analogues. The carbocyclic ribose-5-phosphate analogues were found to be inhibitors, rather than substrates, for 5-phosphoribosyl α-1-pyrophosphate synthetases of both bacterial and human origin. The inhibitory behavior of the analogues is described. The synthesis of analogues 8 and 19 of d-ribose-5-phosphate is described. These analogues were found to be inhibitors, rather than substrates, for 5-phosphoribosyl α-1-pyrophosphate (PRPP) synthetases of both bacterial and human origin.