Pteridines - Part CXIII - Protection of pteridines

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)methylene amino 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.