T. Steinlin, A. Vasella
Mar 1, 2009
Citations
0
Influential Citations
6
Citations
Journal
Helvetica Chimica Acta
Abstract
Acylation of 2-amino-4-(benzyloxy)-6-(methylamino)-5-nitrosopyrimidine (5) with acetic anhydride or chloroacetic anhydride in the presence of 4-(dimethylamino)pyridine (DMAP) led to the C(2)-acylamino derivatives 6 and 7, respectively. In the absence of a base, acetylation did not lead to a product, while chloroacetylation led to the 6-chloropteridine 11. Chloroacetylation in the presence of Hunig's base provided the pteridinone N(5)-oxide 10, suggesting that acylation of 5 is readily reversible, and that the unfavourable equilibrium must be displaced by a follow-up reaction to trap the acylation product. Acylation of 5 with hexadienoyl chloride, followed by intramolecular Diets-Alder reaction, provided the pteridinone 12. A high yielding 1,3-dipolar cycloaddition of the acylnitrone 10 to electron-poor and electron-rich dipolarophiles, followed by spontaneous N,O-bond cleavage, gave the C(6)-substituted pteridinones 19a-19e that were deprotected to the pteridine-4,7(3H,8H)-diones 20a-20e. Substitution of the 6-chloropterin 11 provided the 6-morpholinopteridine 25. Sonogashira coupling yielded the fluorescent [(pteridin-6-yl)ethynyl]-glucopyranoside 26, 6-ethynylpteridine 28, and 6,6'-(ethynediyl)bispteridine 29. The alkyne 28 reacted with Me3SiCl and LiBr in MeCN to produce the bromoalkene 31.