165260-40-2Relevant academic research and scientific papers
Development of methylthiomethyl (MTM) protection for N1 of pyrrolo[2,3-d]pyrimidin-2,4-diones
Edstrom, Eric D.,Feng, Xianqi,Tumkevicius, Sigitas
, p. 759 - 762 (1996)
This paper describes the application of the methylthiomethyl (MTM) protecting group for the N1 position in differentially protected pyrrolo[2,3-d]pyrimidin-2,4-diones. By reaction of selected systems with SO2Cl2 at low temperature resulted in selective formation of N1-chloromethyl derivatives. Subsequent heating in aqueous THF with silica gel afforded the deprotected compounds in good yield. Selectivity in the presence of N3 methoxymethyl (MOM) and benzyloxymethyl (BOM), and N7 p-nitrophenethyl protection was achieved.
A new synthetic route to β-2'-deoxyribosyl-5-substituted pyrrolo[2,3-d]pyrimidines. Synthesis of 2'-deoxycadeguomycin
Edstrom,Wei
, p. 5069 - 5076 (2007/10/02)
A new and flexible synthetic route to β-2'-deoxyribosyl-5-substituted pyrrolo[2,3-d]pyrimidines has been developed. Formation of the pyrrole ring is effected by combining sodium N-(4-nitrophenethyl)glycinate with a differently protected 6-chlorouracil derivative generating a substitution adduct. Heating of this material in acetic anhydride affords the 5-(acetyloxy)pyrrolo[2,3-d]pyrimidine 9 in high yield. Base-mediated removal of the pyrrole protecting group gives free pyrrole 10 which is then glycosylated with 1-chloro-2-deoxy-3,5-ditoluoyl-α-D-erythro-pentofuranose (11) using the sodium salt method. The resulting glycosides 15a,b (α:β, 1:4) are readily separated following hydrolysis of the C-5 acetyloxy group. The subsequently derived pure β-5-(trifluoromethanesulfonyl) derivative 14 undergoes four types of palladium-catalyzed carbon-carbon bond-forming reactions and results in C-5 substituted compounds 15-18. An efficient synthetic route to the pyrrolo[2,3-d]pyrimidine nucleotide analogue, 2'-deoxycadeguomycin (27), is presented. The key transformation involves the conversion of the differentially protected pyrrolo[2,3-d]pyrimidine-2,4-dione base portion in 15 into a protected 2-aminopyrrolo[2,3-d]pyrimidin-4-one 24. An alternative route to 27 was developed which involved prior conversion of the pyrrole-protected precursor 9 into its C-5 triflate derivative 20 followed by palladium-catalyzed carboxylation leading to ester 21. Removal of the pyrrole protecting group and then sodium salt-promoted glycosidation afforded the same β-2'-deoxyribosyl intermediate 15 as prepared earlier. The stereochemistry of glycosidation was found to be dependent upon the electronic effect of the C-5 substituent on the pyrrole ring.
