Pteridines, Part CXIII : Protection of Pteridines

✍ Scribed by Qizheng Yao; Wolfgang Pfleiderer

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: German
• Weight: 184 KB
• Volume: 86
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200390025

✦ Synopsis

Abstract

The low solubility of pterins can drastically be improved by N^2^‐acylation or formation of the N^2^‐[(dimethylamino)methylene] derivatives. Both types of compounds can be alkylated under Mitsunobu conditions to form from N^2^‐acylpterins (see 2 and 3) and their derivatives (see 5, 6, 8, 9, 11, 13, 15, and 17) selectively the O^4^‐alkyl derivatives 22–31, whereas the electron‐donating [(dimethylamino)methyleneamino function in 46–51 gives, in a selective reaction, the N(3)‐substitution (→52–61). N^2^,N^2^‐Dimethylpterins and 18 and 19 and N^2^‐methylpterins 20 and 21 direct alkylation also to the O^4^‐position (→32–35, 38 and 39). Deacylation can be achieved under very mild conditions by solvolysis with MeOH (22→40, 26→41), and displacement of the O^4^‐[2‐(4‐nitrophenyl)ethyl] group proceeds with ammonia at room temperature to the corresponding pteridin‐2,4‐diamines 42–45. Cleavage of the N^2^‐[(dimethylamino)methylene] group works well with ammonia (→62–67). The advantage of applying the 2‐(4‐nitrophenyl)ethyl (npe) group as blocking group is seen in its selective removal by 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) under aprotic conditions without harming the other substituents.