data in which it has been observed3b that when a- and
b-D-ribofuranose-1-phosphate or any phosphate-containing
products were heated with adenine no formation of adenosines
was observed. This is in accord with the formation of unstable
intermediates such as A, B, and C. It is reported15 that in
adenine the 9-N is the prevalent position of a nucleophilic
attack.
In conclusion, our findings demonstrate that it is very
simple to put together the three components to generate
spontaneously in a one-pot reaction and with high chemio-,
regio-, and stereoselectivities, adenosine monophosphate, a
ribonucleotide that is one of the building blocks of RNA.
This process might explain the spontaneous generation of
pre-RNA molecules in the primordial Earth.
Notes and references
1 G. F. Joyce and L. E. Orgel, in The RNA Wordl, ed.
R. F. Gesteland, T. R. Cech and J. F. Atkins, Cold Spring Harbor
Laboratory Press, Cold Spring Harbor, NY, 2006, pp.23–56.
2 J. W. Szostak, Nature, 2009, 459, 171–172.
3 (a) S. J. Benkovic and K. J. Schray, Biochemistry, 1968, 7,
4097–4102; (b) W. D. Fuller, R. A. Sanchez and L. E. Orgel,
J. Mol. Biol., 1972, 67, 25–33; (c) M.-C. Maurel and O. Convert,
Origins Life Evol. Biosphere, 1990, 20, 43–48.
4 C. Ponnamperuma, C. Sagan and R. Mariner, Nature, 1963, 199,
222–226.
5 M. W. Powner, B. Gerland and J. D. Sutherland, Nature, 2009,
459, 239–242.
6 (a) G. Baccolini, C. Boga, M. Mazzacurati and G. Micheletti,
Chem.–Eur. J., 2009, 15, 597–599; (b) G. Baccolini, C. Boga and
G. Micheletti, Phosphorus, Sulfur Silicon Relat. Elem., 2010, 185,
2303–2315.
7 F. H. Westheimer, Acc. Chem. Res., 1968, 1, 70–78.
8 (a) R. R. Holmes, Acc. Chem. Res., 2004, 37, 746–753;
(b) K. C. Kumara Swamy and N. Satish Kumar, Acc. Chem.
Res., 2006, 39, 324–333; (c) G. Baccolini, C. Boga and
G. Micheletti, J. Org. Chem., 2009, 74, 6812–6818.
9 (a) Y. Yamagata, H. Watanabe, M. Saitoh and T. Namba, Nature,
1991, 352, 516–519; (b) Y. Yamagata, H. Kojima, K. Ejiri and
K. Inamota, Origins Life Evol. Biospheres, 1982, 12, 333–337.
10 (a) Phosphoric Anhydride: Structure, Chemistry and Applications,
ed. D. A. Efedrov, P. M. Zavlin and J. C. Tebby, John Wiley &
Sons Ltd., Chichester, 1999; (b) Y. Yamagata and K. Inomata,
Origins Life Evol. Biospheres, 1997, 27, 339–344.
11 (a) D. Siska, B. McCusker, G. Zandomeneghi, B. H. Meier,
D. Blaser, R. Boese, B. Schweizer, R. Gilmour and D. Dunitz,
Angew. Chem., Int. Ed., 2010, 49, 4503–4505; (b) M. Rundrum and
D. F. Shaw, J. Chem. Soc., 1965, 52–57; (c) R. U. Lemeiux and
J. D. Stevens, Can. J. Chem., 1966, 44, 249–262; (d) E. Breitmaier
and U. Hollstein, Org. Magn. Reson., 1976, 8, 573–575.
12 R. B. Stockbridge, G. K. Schoeder and R. Wolfenden, Bioorg.
Chem., 2010, 38, 224–228.
13 (a) A. W. Schwartz, Chem. Commun., 1969, 1393; (b) R. Saffhill,
J. Org. Chem., 1970, 35, 2881–283; (c) E. Etaix and L. E. Orgel,
J. Carbohydr., Nucleosides, Nucleotides, 1978, 5, 91–110;
(d) Y. Yamagata, H. Inoue and K. Inomata, Origins Life Evol.
Biosphere, 1995, 25, 47–52; (e) S. L. Miller and L. E. Orgel, The
Origins of Life on the Earth, Prentice-Hall, Englewood Cliffs, 1974,
pp. 118–128.
Scheme 2 Proposed reaction mechanism.
formed also by direct attack of TMP on b-adenosyl furanoside.
The hydrolysis of intermediate D gives 20,30-cAMP which by
subsequent hydrolysis gives 20-AMP and 30-AMP. The attack
of TMP on adenosines to give phosphorylated adenosines is
probably driven both by the position of the adenylic moiety
and by the presence of the two OH groups in the cis relative
position of the ribose moiety in the adenosine ribofuranoside
form. In the adenosine ribopyranoside form the position of the
two OH groups is disfavored to form a cyclic phosphate. It is
reported14 that the transformation of ribose into its cyclo-
phosphates belongs to the functionalizations of the ribose
molecule which selects the furanose form from the sugar’s
furanose/pyranose equilibrium. For this reason we found only
adenosine b-ribofuranoside monophosphates, determined by
their 1H NMR. These factors conduct to the preferential
formation of 20,30-cAMP that in aqueous solution can be
hydrolyzed to adenosine-20-phosphate and adenosine-30-
phosphate (Scheme 2). In this manner the 50-hydroxy group
remains free, thus explaining why we could detect neither
50-AMP nor ATP. It is reported13a that when deoxyadenosine
is reacted with TMP, only 30- and 50-monophosphates are
obtained in very low yield (2%) suggesting a disfavored
formation of a 30,50-cyclic phosphate. This is in good accord
with our mechanism which is also in agreement with reported
14 (a) A. Eschenmoser, Science, 1999, 284, 2118–2124;
(b) R. Krishnamurthy, S. Guntha and A. Eschenmoser, Angew.
Chem., Int. Ed., 2000, 39, 2281–2285; (c) B. Bennua-Skalmowski,
K. Krolikiewicz and H. Vorbruggen, Tetrahedron Lett., 1995, 36,
7845–7848.
15 (a) R. Shapiro, Ann. N. Y. Acad. Sci., 1969, 163, 624–630;
(b) A. E. Baeasley and M. Rasmussen, Aust. J. Chem., 1981, 34,
1107–1116.
c
3642 Chem. Commun., 2011, 47, 3640–3642
This journal is The Royal Society of Chemistry 2011