Study on the reaction mechanism of C-6 lithiation of pyrimidine nucleosides by using lithium hexamethyldisilazide as a base | Zendy

Yuichi Yoshimura | Zendy; Hiroyuki Kumamoto | Zendy; A. Baba | Zendy; Shingo Takeda | Zendy; H. TANAKA | Zendy

Open Access

Study on the reaction mechanism of C-6 lithiation of pyrimidine nucleosides by using lithium hexamethyldisilazide as a base

Author(s) -

Yuichi Yoshimura,

Hiroyuki Kumamoto,

A. Baba,

Shingo Takeda,

H. TANAKA

Publication year - 2003

Publication title -

nucleic acids symposium series

Language(s) - English

Resource type - Journals

eISSN - 1746-8272

pISSN - 0261-3166

DOI - 10.1093/nass/3.1.17

Subject(s) - chemistry , moiety , uracil , lithium chloride , trimethylsilyl , silylation , pyrimidine , medicinal chemistry , uridine , lithium (medication) , nucleoside , reaction mechanism , combinatorial chemistry , stereochemistry , organic chemistry , catalysis , dna , medicine , rna , biochemistry , gene , endocrinology

The reaction mechanism of C-6 lithiation of uridine mediated by lithium hexamethyldisilazide (LiHMDS) has been investigated. LiHMDS alone dose not lithiate at C-6 of uridine. However, in the presence of an appropriate silylating agent, e.g. trimethylsilyl chloride, the reaction of 1 with LiHMDS allowed to lithiate at C-6 and gave the corresponding C-6 silylated product 2. The experimental results shown below revealed that O-4 (N-3) of uracil moiety may be temporarily masked by silylation, which triggers the C-6 lithiation by lowering the pKa of H-6. The reaction could efficiently be applied to the synthesis of 6,5'-C-cyclouridine, a nucleoside analogue fixed in a specific glycosyl torsion angle by a carbon-carbon bridge.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research