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Synlett 2008(14): 2161-2163  
DOI: 10.1055/s-2008-1078018
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Potentially Prebiotic Passerini-Type Reactions of Phosphates

John D. Sutherland*, Lee B. Mullen, Fabien F. Buchet
School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, UK
Fax: +44(161)2754939; e-Mail: John.Sutherland@manchester.ac.uk;
Further Information

Publication History

Received 6 July 2008
Publication Date:
31 July 2008 (online)

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Abstract

Monoalkyl phosphates can take the place of carboxylic acids in the Passerini reaction, but excesses of aldehyde and isonitriles are required, and transfer of the phosphate to the newly formed hydroxyl group does not take place. By rendering the phosphate addition intramolecular, the efficiency of the reaction is substantially increased. Phosphate transfer can take place when cyanovinyl phosphate is used rather than a monoalkyl phosphate.

Key words

multicomponent reactions - Passerini reaction - phosphates - phosphorylation - prebiotic chemistry

    References and Notes

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5

Glycolaldehyde phosphate disodium salt 8 (55 mg, 0.3 mmol) was dissolved in D2O (3 mL) and the pD was adjusted to 6 using NaOD-DCl solution. Methyl isonitrile (18 µL, 0.3 mmol) was then added and the solution stirred at r.t. overnight.
Data for 11
¹H NMR (500 MHz, D2O): δ = 2.73 (s, 3 H, CH3), 3.96 (ddd, J = 11.4, 7.3, 5.0 Hz, 1 H, CHHOP), 4.02 (ddd, J = 11.0, 6.3, 2.8 Hz, 1 H, CHHOP), 4.25 (app. t, J = 4.1, 3.8 Hz, 1 H, CHOH). ¹³C NMR (75 MHz, D2O): δ = 25.6 (CH3), 66.3 (CH2OP), 71.6 (CHOH), 174.3 (CONHCH3). ³¹P NMR (81 MHz, D2O): δ = 1.32 (t, J = 6.4 Hz).

8

Glycolaldehyde 19 (15 mg, 0.25 mmol) and disodium cyanovinylphosphate (18, 145 mg, 0.75 mmol) were dissolved in D2O (3 mL) and the pD was adjusted to 6 using NaOD-DCl solution. Methyl isonitrile (14 µL, 0.25 mmol) was then added and the solution stirred at r.t. overnight.
Data for 20
¹H NMR (500 MHz, D2O): δ = 2.74 (s, 3 H, CH3), 3.81 (dd, J = 12.0, 3.2 Hz, 1 H, CHHOH), 3.85 (dd, J = 12.3, 2.8 Hz, 1 H, CHHOH), 4.44 (app. dt, J = 9.6, 3.2, 2.8 Hz, 1 H, CHOP). ¹³C NMR (75 MHz, D2O): δ = 25.7 (CH3), 63.3 (CH2OH), 75.2 (CHOP). ³¹P NMR (81 MHz, D2O): δ = 2.14 (d, J = 8.9 Hz). ESI-MS: m/z = 198 (87) [M-]. HRMS: m/z calcd for C4H9O6NP [M-]: 198.0173; found: 198.0181.
Data for 21 ¹H NMR (500 MHz, D2O): δ = 2.72 (s, 3 H, CH3), 3.72 (dd, J = 11.7, 4.9 Hz, 1 H, CHHOH), 3.76 (dd, J = 12.0, 3.5 Hz, 1 H, CHHOH), 4.16 (dd, J = 4.6, 3.6 Hz, 1 H, CHOH). ¹³C NMR (75 MHz, D2O): δ = 25.6 (CH3), 63.3 (CH2OH), 72.3 (CHOH). ESI-MS: m/z = 142 (100) [M + Na+].

9

It is likely that the cyanoacetaldehyde generated from 18 underwent aldol dimerisation (ref. 6). The resultant co-product would not have been clearly detectable by ¹H NMR analysis because of (partial) hydrogen-deuterium exchange.