1000163-01-8Relevant academic research and scientific papers
Pteridines Part CXVIII. Methanopterin, chemical approach and partial synthesis
Heizmann, Gerhard,Pfleiderer, Wolfgang
, p. 1856 - 1873 (2007)
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) (Scheme2). 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).
