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DOI: 10.1039/C7CC02183F
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), and their reactivity with cyanamide (19) was investigated. nucleophilic phosphorylation. Importantly, we demonstrate
Xylo-16 was readily synthesised and incubation in 1M that acrolein ( ) provides a generational link between a key
phosphate (40 ˚C, pH 7.0) gave oxazole 20 by reversible nucleotide precursor and proteinogenic amino acids (Met
dehydration, but lyxo-13 was not observed. The reaction of 18 Gln and Glu), this new generational link supports the unified
with cyanamide (19) gave a mixture of oxazole 20 and xylo-16 origins of these two distinct classes of metabolite.
6
3
,
,
but again lyxo-13 was not observed (ESI Fig. S21), which The EPSRC (EP/K004980/1) and the Simons Foundation
supported the observation that lyxo-13 was not obtained from (318881) supported this work.
the reaction of epoxide 12 and phosphate.
1
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Scheme 5. Synthesis of
18) and their reaction with cyanamide (19).
CuSO , H SO , (CH CO, 4 d, r.t. (ii) 0.1M HCl, 3 h, r.t., 44% over two steps.
iii) (PhO) POCl, CH Cl , pyridine, 7 h, 0°C, 90%. (iv) H , PtO , MeOH, 16 h, r.t.
7%. (v) H O, 16 h, 50°C, quant. (vi) 19, NH OH, H O, 64% isolated yield (>95%
-lyxose-5-phosphate 18: (vii) H SO , (CH CO, 2 h, r.t. 93%.
POCl, CH Cl , pyridine, 6 h, 0°C, 92%. (ix) H , PtO , MeOH, 18 h, r.t.
quant. (x) H O, 16 h, 50 °C, quant. (xi) 19, NH OH, H O, (70% (20) and 30%
16) NMR yield).
D
-xylose-5-phosphate (17) and
D-lyxose-5-phosphate
(
D
-xylose-5-phosphate 17: (i)
4
2
4
3 2
)
(
9
2
2
2
2
2
2
4
2
2
017,
(a) R. A. Sanchez and L. E. Orgel, J. Mol. Biol., 1970, 47, 531–
43. (b) C. Anastasi, M. A. Crowe and J. D. Sutherland, J. Am.
9, 303–309.
NMR yield).
viii) (PhO)
D
2
4
3 2
)
3
4
5
6
(
2
2
2
2
2
5
2
4
2
(
Chem. Soc., 2007, 129, 24–25.
M. W. Powner, C. Anastasi, M. A. Crowe, A. L. Parkes, J.
Raftery and J. D. Sutherland, ChemBioChem 2007,
179.
(a) M. Halmann, R. A. Sanchez and L. E. Orgel, J. Org. Chem.,
969, 34, 3702–3703. (b) R. Krishnamurthy, S. Guntha and A.
8, 1170-
1
Finally, given the close biochemical relatioship between amino
acids and nucleotides, we turned our attention to prebiotic
amino acid synthesis. Analysis of the proteinogenic amino
1
Eschenmoser, Angew. Chem. Int. Ed., 2000, 39, 2281–2285.
(a) J. P. Richard, J. Am. Chem. Soc., 1984, 106, 4926–4936. (b)
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acids suggested a clear link between glycidalehyde (7) and the
amino acids methionine (Met), glutamic acid (Glu) and
glutamine (Gln).
2
014, 389, 18–24.
A. J. Coggins and M. W. Powner, Nat. Chem. 2017,
17.
7
8
9
9, 310–
Met
methylthio)propanal (21) and 3-(cyano)propanal (22), which
are in turn accessed from by Michael addition of
methanethiol (23) or cyanide, respectively (Scheme 6).
Therefore, we incubated (140mM) in water at room
temperature with 23 (saturated, pH 7.0) or potassium cyanide
700mM, pH 9.2). Pleasingly, we observed smooth conversion 10 J. E. Van Trump and S. L. Miller, Science, 1972, 178, 859–860.
, Gln and Glu acid can be synthesised from 3-
3
(
M. W. Powner, J. D. Sutherland and J. W. Szostak, Synlett,
2011, 14, 1956–1964.
6
6
b
1
0,11
The stability of
1.5, 7.2, and 12.0) nucleophilicity is pH dependent and
limited phosphorylation of was observed at pH 4.0–5.0
7%, 168 h).
4-3P increases at pH <5, but phosphate (pKa
=
6
7
(
(
of
6
to aldehyde 21 (94%) and the cyanohydrin of aldehyde 22 11 Y. Wolman, W. J. Haverland and S. L. Miller, Proc. Natl. Acad.
Sci. USA, 1972, 69, 809–811.
(95%), respectively. Subsequently, aldehydes 21 and 22 were
1
1
2 G. B. Payne, J. Am. Chem. Soc., 1959, 81, 4901–4904.
3 J. F. Kasting, H. D. Holland and J. R. Pinto, J. Geophys. Res.,
readily converted to aminonitriles 24 and 25 via Strecker
reaction in water.
1
987, 90, 10497–10510.
1
1
1
1
4 S. Pitsch, E. Pombo-Villar and A. Eschenmoser, Helv. Chim.
Acta, 1994, 77, 2251–2285.
5 C. Anastasi, M. A. Crowe, M. W. Powner and J. D. Sutherland,
Angew. Chem. Int. Ed., 2006, 45, 6176–6179.
6 S. Islam, D.-K. Bucar and M. W. Powner, Nat. Chem., 2017,
DOI: 10.1038/nchem.2703.
7 M. W. Powner and J. D. Sutherland, Angew. Chem. Int. Ed.,
2
010, 49, 4641–4643.
Scheme 6. Prebiotic synthesis of amino acids methionine (Met), glutamine 18 Y. B. Tewari and R. N. Goldberg, Biophys. Chem. 1985, 22
Gln), and glutamic acid (Glu) from acrolein (6).
,
(
1
97–204.
9 (a) H.-J. Kim, A. Ricardo, H. I. Illangkoon, M. J. Kim, M. A.
Carrigan, F. Frye and S. A. Benner, J. Am. Chem. Soc. 2011,
33, 9457–9468. (b) Á. Vázquez-Mayagoitia, S. R. Horton, B.
1
1
These studies demonstrate the first prebiotically plausible
synthesis of aminooxazoline-5'-phosphates in water by a facile
G. Sumpter, J. Šponer, J. E. Šponer and M. Fuentes-Cabrera,
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