open access

https://hdl.handle.net/2115/46971

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

英語

2000

Taylor & Francis

Nucleosides, Nucleotides and Nucleic Acids

19(1-2)

175-187

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-N6-trichloroacetyl-2’,3’-0-isopropylideneadenosine 9c gave N-1-carbocyclic derivative, which was deprotected to give 5’,5”-diol derivatives 18. When 18 was treated with POCl3 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.

学術雑誌論文

Accepted Manuscript

This is an electronic version of an article published in Nucleosides, Nucleotides & Nucleic Acids, 19(1-2), 175-187, 2000. Nucleosides, Nucleotides & Nucleic Acids is available online at: http://www.informaworld.com/openurl?genre=article&issn=15257770&volume=19&issue=1-2&spage=175

1525-7770