Journal of the American Chemical Society HRMS ESI [M+H+] calc. for C6H13N6O2S 269.0821; obs. 269.0832. Cambridge Crystallographic Data Centre deposition number 864232. 24: Yield >70% lyxo-24: Rf = 0.20 (CH2Cl2/MeOH 7:3). IR (solid, cm−1): 3344, 3106, 2917, 2833, 1627, 1553. 1H NMR (400 MHz; DMSO): δH 7.14 (s, 1H, Ar), 6.90 (s, 2H, NH2), 6.59 (bs, 1H, NH2), 6.35 (s, 1H, NH), 5.93 (d, J = 6.1, 1H, H−(C1′)), 4.98 (d, J = 6.1, 1H, HO), 4.93 (t, J = 5.4, 1H, HO), 4.19 (dd, J = 7.6, 6.2, 1H, H−(C2′)), 3.59−3.54 (m, 1H, H−(C4′)), 3.49 (ABX, J = 10.9, 5.0, 1H, H− (C5′)), 3.46−3.41 (m, inc. J = 10.9, 1H, H−(C5′)), 3.36−3.34 (m, inc. J = 7.6 Hz, 1H, H−(C3′)). 13C NMR (100 MHz; DMSO): δC 166.6, 160.5, 148.7, 141.2, 128.6, 110.8, 78.38, 78.35, 71.2, 63.2, 53.3, 50.5. HRMS ESI [M + Na+] calc. for C10H14N6O3SNa 321.0746; obs. 321.0742. Cambridge Crystallographic Data Centre deposition number 864233. xylo-24: Rf = 0.20 (CH2Cl2/MeOH 7:3). IR (solid, cm−1): 3309, 3125, 2936, 2835, 1632, 1565. 1H NMR (400 MHz; D2O): δH 7.26 (s, 1H, Ar), 5.94 (d, J = 5.8, 1H, H−(C1′)), 4.21 (t, J = 6.7, 1H, H− (C2′)), 3.73 (m, 1H, H−(C4′)), 3.69 (ABX, J = 11.8, 4.5, 1H, H− (C5′)), 3.64 (ABX, J = 11.8, 4.5, 1H, H−(C5′)), 3.52 (dd, J = 7.5, 1.9, 1H, H−(C3′)). 1H NMR (400 MHz; DMSO): δH 7.05 (s, 1H, Ar), 6.99 (s, 1H, NH2), 6.67 (bs, 1H, NH2), 6.18 (s, 1H, NH), 6.01 (d, J = 6.3, 1H, H−(C1′)), 5.44 (d, J = 6.0, 1H, HO), 4.85 (t, J = 5.5, 1H, HO), 4.55 (d, J = 6.1, 1H, H−(C2′)), 3.69 (d, J = 8.3, 1H, H−(C4′)), 3.54 (ABX(OH), J = 11.3, 5.5, 1H, H−(C5′)), 3.47 (ABX(OH), J = 11.3, 5.5, 1H, H−(C5′)), 3.20 (m, 1H, H−(C3′)). 13C NMR (101 MHz; DMSO): δC 166.5, 165.9, 141.0, 127.9, 111.5, 100.0, 79.7, 75.1, 63.5, 53.5. HRMS ESI [M + Na+] calc. for C10H14N6O3SNa 321.0746; obs. 321.0750. Cambridge Crystallographic Data Centre deposition number 864234. ASSOCIATED CONTENT *S Supporting Information NMR and IR spectra, photographic images of sublimation experiments, crystallographic information (CIFs) and a stereo- chemical model for the addition of thiazole 7 to imine 21. This material is available free of charge via the Internet at http:// pubs.acs.org. AUTHOR INFORMATION Corresponding Author matthew.powner@ucl.ac.uk Notes The authors declare no competing ﬁnancial interest. ■ ACKNOWLEDGMENTS M.W.P. was supported by a fellowship from the Harvard Origins Initiative, the Howard Hughes Medical Institute and University College London. This research was funded in part by Grant CHE-0809413 from the NSF. J.W.S. is an Investigator of the Howard Hughes Medical Institute. The authors thank J.C. Blain, Dr. R.B. Moreno, Dr. A. Ricardo, and Prof. J.D. Sutherland for helpful discussions and The Mass Spectrometry Facility at the FAS Center for Systems Biology for mass spectrometry support. REFERENCES (1) (a) Powner, M. 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H. 1957, US PAT. 2,850,504. (14) Signiﬁcant H−(C4) exchange was observed in D2O. (15) Caraoni, P. C.; Reboul, J. P. Acta Crystallogr. 1982, B38, 1255. (16) Cambridge Crystallographic Data Centre deposition number for 7 is 864225. (17) 16 is a product of HCN-oligomerization and known nucleobase precursor.18 Notably, HCN also is required for Strecker synthesis.8 (18) (a) Oro, J. Biochem. Biophys. Res. Commun. 1960, 2, 407. (b) Lowe, C. U.; Rees, M. W.; Markham, R. Nature 1963, 199, 219. (19) Cambridge Crystallographic Data Centre deposition numbers for 17, erythro-18, threo-18, threo-19, and threo-20 are 864226, 864227, 864228, 864229, and 864230, respectively. (20) Proposed prebiotic nucleotide syntheses must be evaluated for their potential to yield alternative structures capable of base-pairing. Constitutionally, 3 (C2) and 22 (C3) can react with azoles (C2 sugar- synthon) to furnish threose nucleic acid (TNA; C4-sugar)21 and DNA/RNA (C5-sugar) precursors, respectively.1 (21) Schöning, K.; Scholz, P.; Guntha, S.; Wu, X.; Krishnamurthy, R.; Eschenmoser, A. Science 2000, 290, 1347. (22) Cambridge Crystallographic Data Centre deposition numbers for erythro-23, threo-23, lyxo-24, and xylo-24 are 864231, 864232, 864233, and 864234, respectively. (23) (a) Anastasi, C.; Crowe, M. A.; Powner, M. W.; Sutherland, J. D. Angew. Chem. 2006, 118, 6322; Angew. Chem., Int. Ed. 2006, 45, 6176. (b) Sagi, V. S.; Karri, P.; Hu, F; Krishnamurthy, R. Angew. Chem. 2011, 123, 8277; Angew. Chem., Int. Ed. 2011, 50, 8127. (24) The formation of aminal 25 was observed during the formation of 2-aminothiazole 7 in presence of stoichiomtric glycolaldehyde 3 and mercaptoacetaldehyde 6 and substiochiometric cyanamide 2. (25) Cambridge Crystallographic Data Centre deposition numbers for 25 and D-27 are 864235 and 864236, respectively. 13894 dx.doi.org/10.1021/ja306176n | J. Am. Chem. Soc. 2012, 134, 13889−13895