Pteridines. Part CXVII

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 ).