Pteridines. Part CXVIII

Our approach to achieve a partial synthesis of methanopterin ( 1 ) started from 6‐acetyl‐O⁴‐isopropyl‐7‐methylpterin ( 20 ) which was obtained either by condensation from 6‐isopropoxypyrimidine‐2,4,5‐triamine ( 19 ) and pentane‐2,3,4‐trione ( 6 ) or from 6‐isopropoxy‐5‐nitrosopyrimidine‐2,4‐diamine ( 21 ) and pentane‐2,4‐dione (=acetylacetone; 22 ) (Scheme 2). NaBH₄ reduction of 20 led to 6‐(1‐hydroxyethyl)‐O⁴‐isopropyl‐7‐methylpterin ( 23 ) which was converted into the corresponding 6‐(1‐chloroethyl) and 6‐(1‐bromoethyl) derivatives 24 and 25 . A series of nucleophilic displacement reactions in the side chain and at position 4 were performed as model reactions to give 26 – 29, 32 – 35 , and 39 – 41 . Hydrolysis of the substituents at C(4) led to the corresponding pterin derivatives 30, 31, 36 – 38 , and 42 . Analogously, 25 reacted with 1‐(4‐aminophenyl)‐1‐deoxy‐2,3: 4,5‐di‐O‐isopropylidene‐D ‐ribitol ( 43 ), prepared from N‐(4‐bromophenyl)benzamide ( 47 ) via 49 and 50 to give 1‐{4‐{{1‐2‐amino‐7‐methyl‐4‐(1‐methylethoxy)pteridin‐6‐yl]ethyl}amino}phenyl}‐1‐deoxy‐D ‐ribitol ( 44 ) in 62% yield (Scheme 3). Acid cleavage of the isopropylidene groups at room temperature led to 45 and on boiling to 1‐{4‐{1‐(2‐amino‐3,4‐dihydro‐7‐methyl‐4‐oxopteridin‐6‐yl)ethyl]amino}phenyl}‐1‐deoxy‐D ‐ribitol ( 46 ). The next step, however, attachment of the ribofuranosyl moiety with 55 or 56 to the terminal 1‐deoxy‐D ‐ribitol OH group could not been achieved. The second component, bis(4‐nitrobenzyl) 2‐{(2‐cyanoethoxy)(diisopropylamino)phosphino]oxy}pentanedioate ( 61 ), to built‐up methanopterin ( 1 ) was synthesized from 2‐hydroxypentanedioic acid ( 59 ) and worked well in another model reaction on phosphitylation with N⁶‐benzoyl‐2′,3′‐O‐isopropylideneadenosine and oxidation to give 62 (Scheme 6).