Nonenzymatic Oligomerization of Ribonucleotides on Guanosine‐Rich Templates: Suppression of the Self‐Pairing of Guanosine

Abstract

COMMUNICATIONSpear to be generated at intermediate acidities; this phenomenon requires further investigation.Given the controversial nature of our findings, we decided to prepare 4 under our conditions (Scheme 2). Only modest yields (7.7 %) were obtainable, but this reaction is no doubt complicated by the presence of the third aldehyde grouping. 'HNMR data again only showed the presence of the expected resonances; the extra peaks noted by Berlin et al. were absent, even for spectra recorded at 500 MHz ( Figure 1B). The UV/Vis spect r~m [ '~] for the free base gave much higher molar absorptivity values than reported (the Soret band at 434 nm gave E = 87 600; E < 40000 was reported by Berlin[']), which is in accord with our expectations for a porphyrin analog of this type. It is also worth noting that our samples were obtained as deep purple microneedles and not as the dark green/brown solid previously isolated. ['] Our new findings demonstrate that no unusual conformation-a1 or tautomeric processes are occurring for carbaporphyrins 2 or 4. The anomalous spectroscopic data reported by Berlin et al. [7.8] are most likely due to impurities arising from the less favorable reaction conditions used in their studies.[", Experimental Procedure 2: Dicarboxylic acid 1 [17] (100 mg) was stirred with TFA (1 mL) under an atmosphere of nitrogen for 10 min. CH,CI, (I9 mL) was added followed immediately by 1,3-difonnylindene (38 mg), and the mixture stirred for a further 2 h. The mixture was neutralized by the dropwise addition of Et,N, DDQ (50 mg) added, and the resulting solution stirred for an additional 1 h. The mixture was washed with water and purified by chromatography on neutral Grade 3 alumina with CH,CI, as eluant, and a dark brown fraction was collected. Repeated chromatography on a silica column with CH,CI, as eluant gave the product asa broad, brown band. Recrystallization from CHCI,/MeOH afforded 2 (47 mg, 43 %) as fluffy copper/bronze-colored crystals. M.p. = 270 "C (decomp.); UV/Vis (1 % Et,N/CH,CI,): i.,,, (Ig,,s) =

Nonenzymatic Template-Directed Reactions on Altritol Oligomers, Preorganized Analogues of Oligonucleotides

“…The failure of template reactions in systems where the B form of DNA is stable illustrates this point. [13,14,16] The results presented above reinforce the suggestion of Göbel and co-workers [13,14] that the work of Wu et al [2,5,6] may represent a somewhat too pessimistic view on the prospects for nonenzymatic replication of RNA. In many earlier experiments, as in those reported above, the primer consisted of an oligodeoxynucleotide terminated by a single ribonucleotide residue and the template was an oligodeoxynucleotide.…”

“…With this arrangement, the template ± primer double helix may not adopt an A conformation around the 3'-terminus of the primer. [13,14] Therefore, the primer extension reaction may be inhibited. Clearly, more detailed information transfer experiments with RNA primers and templates are now necessary, and they are underway.…”

“…A related effect on DNA and RNA templates has been reported. [13,14] The authors suggested that the structure of the primer ± template duplex has a substantial effect on the efficiency of the reaction, and that the duplexes with the A structure of nucleic acid double helices promote the most efficient primer extension.…”

The Origins of the RNA World

“…If poly(C) is incubated with an equimolar mixture of the four 2-MeImpNs (N ¼ G, A, C, or U), less than 1% of the product consists of noncomplementary nucleotides (Inoue and Orgel 1982). Subsequent experiments suggested that this and the related reactions discussed later occur preferentially within the context of double helices that have a structure resembling the A form of RNA (Kurz et al 1997(Kurz et al , 1998Kozlov et al 1999Kozlov et al , 2000.…”

Prebiotic Chemistry and the Origin of the RNA World

“…There is now substantial evidence that the templatedirected oligomerization of 2-Me-imidazole derivatives proceeds best in double helices that adopt the A-form nucleic acid structure (Kurz et al, 1997(Kurz et al, , 1998Kozlov et al, 1999bKozlov et al, , 2000b. RNA sequences are superior to DNA sequences as templates, but the general features of the reactions are similar for RNA and DNA templates (Zielinski et al, 2000).…”