Synthesis of pyrrole-fused pteridines via Pictet-Spengler reaction and Smiles rearrangement

ORGN 903

Jinbao Xiang, Lianyou Zheng, Feng Chen, Qun Dang, and Xu Bai, xbai@jlu.edu.cn. The Center for Combinatorial Chemistry and Drug Discovery, The College of Chemistry, Jilin University, Changchun, 130012, China
A novel methodology was developed for the efficient synthesis of 5,6-dihydropyrrolo[1, 2-f]pteridine derivatives via Pictet-Spengler reaction followed by Smiles Rearrangment (shown in Scheme 1). Pyrimidine-substituted amino alcohol 1 was converted by Parikh-Doering Oxidation to aldehyde 2, which, without purification, underwent a Pictet-Spengler like cyclization with an amine in presence of trifluoroacetic acid to yield a pyrimidodiazepine 3. Diazepine 3 was easily converted to the more stable six-membered ring analog 4 through Smiles like rearrangement by heating. This new method complements the existing chemistries for the preparation of pyrrolo[1, 2-f]pteridine derivatives, and can be applied to design and synthesis of more structurally diversified molecules.

 

Combinatorial, Parallel, and Solid-Phase Chemistry
8:00 AM-12:00 PM, Thursday, 14 September 2006 Moscone Center -- Room 132, Oral

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006