Abstract
A series of side chain reactions starting from the 6‐ and 7‐styryl‐substituted 1,3‐dimethyllumazines 1 and 21 as well as from the 6‐ and 7‐[2‐(methoxycarbonyl)ethenyl]‐substituted 1,3‐dimethyllumazine 2 and 22 were performed first by addition of Br~2~ to the CC bond forming the 1′,2′‐dibromo derivatives 3, 4, 24, and 26 in high yields (Schemes 1 and 3) (lumazine=pteridine‐2,4(1__H__,3__H__)‐dione). Treatment of 3 with various nucleophiles gave rise to an unexpected tele‐substitution in 7‐position and elimination of the Br‐atoms generating 7‐alkoxy‐ (see 5 and 6), 7‐hydroxy‐ (see 7) and 7‐amino‐6‐styryl‐1,3‐dimethyllumazines (see 8–11) (Scheme 1). On the other hand, 4 underwent, with dilute DBU (1,8‐diazabicyclo[5.4.0]undec‐2‐ene), a normal HBr elimination in the side chain leading to 18, whereas treatment with MeONa afforded a more severe structural change to 19. Similarly, 24 and 26 reacted to 27, 32, and 33 under mild conditions, whereas in boiling NaOMe/MeOH, 24 gave 7‐(2‐dimethoxy‐2‐phenylethyl)‐1,3‐dimethyllumazine (30) which was hydrolyzed to give 31 (Scheme 3). From the reactions of 4 and 24 with DBU resulted the dark violet substance 20 and 25, respectively, in which DBU was added to the side chain (Scheme 2). The styryl derivatives 1 and 21 could be converted, by a Sharpless dihydroxylation reaction, into the corresponding stereoisomeric 6‐ and 7‐(1,2‐dihydroxy‐2‐phenylethyl)‐1,3‐dimethyllumazines 34–37 (Scheme 4). The dihydroxy compounds 34 and 35 were also acetylated to 38 and 39 which, on catalytic reduction followed by formylation, yielded the diastereoisomer mixtures 40 and 41. Deacetylation to 42 and 45 allowed the chromatographic separation of the diastereoisomers resulting in the isolation of 43 and 44 as well as 46 and 47, respectively. Introduction of a 6‐ or 7‐ethynyl side chains proceeded well by a Sonogashira reaction with 6‐ (48) or 7‐chloro‐1,3‐dimethyllumazine (55) yielding 49–51 and 56–58 (Scheme 5). The direction of H~2~O addition to the triple bond is depending on the substituents since the 6‐ (49) and 7‐(phenylethynyl)‐1,3‐dimethyllumazine (56) showed attack at the 2′‐position yielding 53 and 60, in contrast to the 6‐ (51) and 7‐ethynyl‐1,3‐dimethyllumazine (58) favoring attack at C(1′) and formation of 6‐ (52) and 7‐acetyl‐1,3‐dimethyllumazine (59).