A Selective and Efficient Method for the Deprotection of N-Benzyloxymethyl (BOM) Protecting Groups from Pyrimidine and Dihydropyrimidine Ring Systems

References

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• The iodo-, trifluoromethyl- and methyl esters 4, 3 and 1 are susceptible to elimination or hydrolysis under basic conditions.
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• See compounds 1–7 in the Table. The unsaturated functions at C-5 prohibit the use of catalytic hydrogenation to remove either benzyl or benzyloxymethyl groups.
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• Corresponding BOM and MEM derivatives were prepared by standard N-alkylation procedures and the products were fully characterized by analytical and spectral data.
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• Yields cited in Table I are for chromatographically and spectroscopically homogeneous substances. All the products were identified by comparing with authentic samples by mp, NMR and TLC.
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• N1,N3-di-BOM-5-(trifluoromethyl)uracil (3): 1H nmr (80 MHz, CDCl3) δ 4.63 (2H, s), 4.69 (2H, s), 5.24 (2H, s), 5.44 (2H, s), 7.51 (11H, m). CIMS (CH4) m/z (relative intensity %) 421 (M+H+) (60), 401 (11), 301 (16), 271 (10), 211 (6), 181 (50), 119 (15), 91 (100), EI-HRMS, obsd. 420.1292 (M+) calcd for C21H19F3N2O4, 420. 1296.
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• N1,N3-di-BOM-5-N-iodouracil (4): 1H nmr (80 MHz, CDCl3) δ 4.59 (2H, s), 4.68 (2H, s), 5.17 (2H, s), 5.48 (2H, s), 7.50 (11H, m). CIMS (isobutane) m/z (relative intensity %) 479 (M+H)+ (100), 449 (11), 353 (25), 147 (33), 101 (37), 91 (52). Found C, 50.18; H, 4.17; N, 5.6 calcd for C20H19IN2O4, C, 50.22; H, 4.00; N, 5.85.
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• N3-BOM-2′,3′,5′-tri-O-acetyl uridine (5): 1H nmr (200 MHz, CDCl3) δ 2.09 (3H, s), 2.12 (3H, s), 2.13 (3H, s), 4.35 (3H, m), 4.68 (2H, m), 5.34 (2H, m), 5.46 (2H, s), 5.78 (1H, d, J = 7.8 Hz), 5.98 (1H, d, J = 4 Hz), 7.34 (6H, m). CIMS (NH3) m/z (relative intensity %) 508 (M+NH3+H)+ (100), 491 (M+H)+ (10), 466 (M-OAc) (75), 424 (M-20Ac) (37), 382 (M-30Ac) (2), 259 (sugar moiety) (7), CI-HRMS, obsd. 491.1690 (M+H)+ calcd for C23H26N2O10+H+, 491.1666.
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• Methyl N1,N3-di-(MEM)-5-iodo-orotate (6): 1H nmr (80 MHz, CDCl3) δ 3.33 (3H, s), 3.34 (3H, s), 3.81–3.42 (8H, m), 3.99 (3H, s), 5.41 (2H, s), 5.53 (2H, s). CIMS (CH4) m/z (relative intensity %) 473 (M+H)+ (9), 397 (42), 323 (19), 89 (100), CI-HRMS, obsd, 473.0421 (M+H)+ calcd for C14H21IN2O8+H, 473.0401.
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• Methyl N1,N3-di-(BOM)-5,6-dihydroorotate (7): 1H nmr (80 MHz, CDCl3) δ 2.46 (1H, dd, J = 16.8, 7.2 Hz), 2.94 (1H, dd. J = 2, 16.8 Hz), 3.66 (3H, s), 4.23 (1H, dd, J = 2, 7.2 Hz), 4.48 (1H, d, J = 10.8 Hz), 4.62 (2H, s), 4.70 (1H, d, J = 10.8 Hz), 4.91 (1H, d, J = 10.8 Hz), 5.27 (2H, d, J = 10 Hz), 5.28 (1H, d, J = 10.8 Hz), 5.41 (1H, d, J = 10 Hz), 7.32 (10H, s), CI-HRMS, obsd. 413.1720 (M+H)+ calcd for C22H24N2O6+H+, 413.1713.
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• Methyl N3-BOM-5,6-dihydroorotate (8) m. p. 97°C: 1H nmr (80 MHz, DMSO-d6) δ 2.65 (1H, dd, J = 3.7, 16.8 Hz), 3.14 (1H, dd, J = 6.8, 16.8 Hz), 3.67 (3H, s), 4.25 (1H, ddd, J = 3.8, 3.7, 6.8 Hz), 4.49 (2H, s), 5.17 (2H, s), 7.32 (5H, s), 8.34 (1H, brd, J = 3.8 Hz). CIMS (CH4), m/z (relative intensity %), 369 (M+H)+ (9), 351 (14), 2′ (90), 91 (100). Found C, 57.78; H, 5.46; N, 9.60. calcd for C20H20N2O5, C, 57.73; H, 5.19; N, 9.62.
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• N1,N3-di(BOM)-6-methyl-5,6-dihydrouracil (10). 1H nmr (200 MHz, CDCl3) δ 1.21 (3H, d, J = 6.8 Hz), 2.43 (1H, dd, J = 3.7, 15.5 Hz), 2.52 (1H, dd, J = 5.4, 15.5 Hz), 3.73 (1H, m), 4.52 (1H, d, J = 12.1 Hz), 4.61 (1H, d, J = 12.1 Hz), 4.67 (2H, s), 4.79 (1H, d, J = 10.7 Hz), 5.26 (1H, d, J = 10.7 Hz), 5.30 (1H, d, J = 10.2 Hz), 5.42 (1H, d, J = 10.2 Hz), 7.32 (10H, m). CIMS (isobutane), m/z (relative intensity %) 369 (M+H)+ (15), 325 (6), 261 (100), CI-HRMS, obsd, 369.1825 (M+H) calcd for C21H24N2O4, 369.1814.
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