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Acylation of a 6‐(Methylamino)‐5‐nitrosopyrimidine and 1,3‐Dipolar Cycloaddition of an 8‐Methylisoxanthopterin N(5) ‐Oxide. Synthesis of C(6) , N(8) ‐Disubstituted Isoxanthopterins
Author(s) -
Steinlin Thomas,
Vasella Andrea
Publication year - 2009
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200900009
Subject(s) - chemistry , acylation , acetic anhydride , cycloaddition , medicinal chemistry , pyridine , 1,3 dipolar cycloaddition , intramolecular force , stereochemistry , organic chemistry , catalysis
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 Hünig '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 Diels – 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(3 H ,8 H )‐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 Me 3 SiCl and LiBr in MeCN to produce the bromoalkene 31 .