Nucleosides and Nucleotides. 192. Toward the Total Synthesis of Cyclic ADP-Carbocyclic-Ribose. Formation of the Intramolecular Pyrophosphate Linkage by a Conformation-Restriction Strategy in a Syn-form Using a Halogen Substitution at the 8-Position of the Adenine Ring

• Published in: Nucleosides, nucleotides & nucleic acids nucleotides & nucleic acids, 2000-01, Vol.19 (1-2), p.175-187
• Main Authors: Sumita, Yuji, Shirato, Michiyo, Ueno, Yoshihito, Matsuda, Akira, Shuto, Satoshi
• Format: Article
• Language: English
• Subjects: Adenine - chemistry; Adenosine Diphosphate Ribose - analogs & derivatives; Adenosine Diphosphate Ribose - chemical synthesis; Adenosine Diphosphate Ribose - chemistry; Cyclic ADP-Ribose; Diphosphates - chemistry; Halogens - chemistry; Magnetic Resonance Spectroscopy
• ISSN: 1525-7770; 1532-2335
• DOI: 10.1080/15257770008033002

The synthesis of cyclic ADP-carbocyclic-ribose (2), as a stable mimic for cyclic ADP-ribose, was investigated. Construction of the 18-membered backbone structure was successfully achieved by condensation of the two phosphate groups of 19, possibly due to restriction of the conformation of the substrate in a syn-form using an 8-chloro substituent at the adenine moiety. SN2 reactions between an optically active carbocyclic unit 8, which was constructed by a previously developed method, and 8-bromo-N 6 -trichloroacetyl-2′,3′-O-isopropylideneadenosine 9c gave N-1-carbocyclic derivative, which was deprotected to give 5′,5′-diol derivatives 18. When 18 was treated with POCl 3 in PO(OEt) 3 , the bromo group at the 8-position was replaced to give N-1-carbocyclic-8-chloroadenosine 5′,5′-diphosphate derivative 19 in 43% yield. Treatment of 19 with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride gave the desired intramolecular condensation product 20 in 10% yield. This is the first chemical construction of the 18-membered backbone structure containing an intramolecular pyrophosphate linkage of a cADPR-related compound with an adenine base.