1182
S. A. Adediran et al. / Bioorg. Med. Chem. 9 (2001) 1175±1183
product was dissolved in acetone and precipitated by
addition of pentane. The collected solid was then dis-
solved in ether, the solution ®ltered on a hydrophobic
®lter (0.45 mm) and the solvent evaporated to give the
duct was directly acylated by phenylacetyl chloride as
previously described to give the title acid 8m which was
puri®ed by chromatography (ethyl acetate:acetic acid
95:5), aording 97 mg (75%) of the title product.
title lactone 7; mp 226±229 ꢂC; H NMR (CD3COCD3)
1
d: 3.61 (s, 2H, ArCH2), 5.46 (d, J=6.44, 1H, CH), 7.18
to 7.32 (m, 5H, Ar), 7.38 (d, J=7.72, 1H, H5), 7.64 (d,
J=1.29, 1H, H2), 7.83 (dd, 1H, H6), 8.48 (d, 1H, NH).
13C NMR (CD3COCD3) d: 42.71 (CH2Ar), 52.09 (CH),
111.86±l36.24 (C Ar), 155.11 (C phenol), 166.81, 171.53
and 173.26 (CO2 and CON). MS (ES): m/z 312 (MH+),
334 (M+Na+), and 350 (M+K+). HRMS (ESÀ) calcd
for [C17H12NO5]À: 310.0715. Found: 310.0719.
Acknowledgements
This research was supported by a National Institutes of
Health grant to RFP.
References and Notes
1. Levy, S. B. Sci. Am. 1998, 278, 46.
2. Pratt, R. F.; Govardhan, C. P. Proc. Natl. Acad. Sci.
U.S.A. 1984, 81, 1302.
3. Govardhan, C. P.; Pratt, R. F. Biochemistry 1987, 26, 3385.
4. Adam, M.; Damblon, C.; Plaitin, B.; Christiaens, L.; Frere,
J.-M. Biochem. J. 1990, 270, 525.
5. Xu, Y.; Soto, G.; Hirsch, K. R.; Pratt, R. F. Biochemistry
1996, 35, 3595.
6. Cabaret, D.; Adediran, S. A.; Garcia Gonzalez, M. J.;
Pratt, R. F.; Wakselman, M. J. Org. Chem. 1999, 64, 713.
7. Adediran, S. A.; Cabaret, D.; Pratt, R. F.; Wakselman, M.
Bioorg. Med. Chem. Lett. 1999, 9, 341.
8. Cabaret, D.; Garcia Gonzalez, M.; Wakselman, M.; Ade-
diran, S. A.; Pratt, R. F. Eur. J. Org. Chem., 2001, 141.
9. Ben-Ishai, D.; Sataty, I.; Bernstein, Z. Tetrahedron 1976,
32, 1571.
10. Lofthouse, G. J.; Suschitzky, H.; Wake®eld, B. J.; Tuck,
B. J. Chem. Soc., Perkin Trans. 2 1979, 1634.
Methyl 3-benzyloxy-4-formyl benzoate (27). Methyl 3-
hydroxy-4-formyl benzoate 26 (178 mg, 0.99 mmol) was
dissolved in anhydrous DMF (6 mL). Dry K2CO3
(400 mg), then benzyl bromide, 0.12 mL (1 equiv) in
DMF (2 mL), were added. The mixture was stirred at
room temperature for 2 h. The product was extracted
into ethyl acetate and the organic phase washed with
water (3Â), dried over MgSO4 and evaporated. The
crude product was puri®ed by chromatography (penta-
ne:ether 3:1), aording 257 mg (96%) of the title pro-
1
duct 27; Rf 0.36; oil; H NMR (CDCl3) d: 3.96 (s, 3H,
CH3), 5.26 (s, 2H, CH2), 7.35±7.50 (m, 5H, Ar), 7.71
(dd, 1H, J=1.3 Hz, J=8.09 Hz, H6), 7.77 (d, 1H, H2),
7.91 (d, 1H, H5), 10.59 (s, 1H, CHO); 13C NMR
(CDCl3) d: 52.84 (COOCH3), 70.97 (OCH2), 114.26±
136.56 (Ar), 160.81 (C phenol), 166.21 (CO), 189.52
(CHO). Anal. calcd for C16H14O4: C, 71.10; H, 5.22.
Found: C, 70.97; H, 5.26.
11. Schouteeten, A.; Chritidis, Y.; Mattioda, G. Bull. Soc.
Chim. Fr. 1978, 248.
12. Barrett, G. C. Chemistry and Biochemistry of the Amino
Acids. Chapman and Hall: London, 1985 p. 246.
13. Williams, R. M.; Hendrix, J. A. Chem. Rev. 1992, 92, 889.
14. In the literature, we could not ®nd an example of the pre-
paration of o-hydroxyphenyl-glycines by these methods.
Treatment of salicylaldehyde cyanohydrin with HCl gave 2,3-
dihydro-2-hydroxy-2H-l-benzofuran-3-one instead of the
2-Amino-2-(20-benzyloxy-40-methoxycarbonyl)phenylace-
tonitrile (28). The aldehyde 27 (162 mg, 0.6 mmol) was
dissolved in methanol (4 mL) and the solution was
added at 0 ꢂC to a mixture of 45 mg of NaCN and 75 mg
of NH4Cl in a 33% aqueous solution of ammonia
(1.5 mL). After the mixture was stirred overnight at
room temperature, the methanol was evaporated, water
was added, and the product extracted with dichloro-
methane. The solution was dried over MgSO4 and eva-
porated. Chromatography (ether:pentane 3:1) gave
120 mg (73%) of the a-aminonitrile 28; Rf 0.38; mp
expected
2,3-dihydro-3-hydroxy-2H-l-benzofuran-2-one.15
Condensation of cyanide anion with salicylaldehyde in the
presence of ammonia led to the 2,3-bis-salicylideneamino-
benzofuran (hydrocyansalide).16 On the other hand, 5-(o-
hydroxyphenyl)hydantoin could not be prepared by the
Bucherer method.17
15. Howe, R.; Rao, B. S.; Heyneker, H. J. Chem. Soc. (C)
1967, 2510.
16. Baldwin, J. E.; Blythin, D. J.; Waight, E. S. J. Chem. Soc.
(C) 1969, 735
17. Harvill, B. K.; Herbst, R. M. J. Org. Chem. 1944, 9, 21.
18. These peaks certainly could lie under the water peak since the
chemical shifts of the methine protons of 6±8 in d6-Me2CO(all as
neutral acids) were d, 5.44, 5.45, and 5.51, respectively.
19. Scheme 6 and the discussion surrounding it is supported
by the observations that the C3-H of 5-nitro-coumaran-2-
one20 and 3-phenyl-coumaran-2-one21 are rapidly exchanged
in D2O. The carbon acid pKas of these compounds are repor-
ted to be 9.720,22 and 8.4,21 respectively; the pKa of the parent
coumaran-2-one is 12.3.21
76 ꢂC; H NMR (CDCl3) d: 2.08 (s, 2H, NH2), 3.94 (s,
1
3H, CH3), 5.10 (s, CH), 5.23 (s, CH2), 7.35±7.50 (m, 5H,
Ar), 7.53 (d, 1H, J=6.07, H5), 7.70 (s, 1H, H2), 7.72 (d,
1H, H6); 13C NMR (CDCl3) d: 43.60 (CH), 52.63
(COOCH3), 70.99 (CH2), 120.37 (CN), 113.20±135.83
(Ar), 155.82 (C phenol), 166.47 (CO). Anal. calcd for
C17H16N2O3: C, 68.90; H, 5.44; N, 9.45. Found: C,
68.92; H, 5.41; N, 9.24,
2-Phenylacetyl-(20-hydroxy-40-carboxy)phenylacetic acid
(8m). The a-aminonitrile 28 was dissolved in 6 M HCI
(2 mL) and heated in a stoppered ¯ask for 16 h at
115 ꢂC. Evaporation to dryness gave 61.5 mg of the
a-amino acid hydrochloride 29, pure by TLC, Rf 0.56
(ethyl acetate:acetic acid 1:1). 1H NMR (CD3OD) d:
5.11 (s, 1H, CH), 7.36 (d, J=7.54 Hz, 1H, H5), 7.54 (d,
J=1.47 Hz, 1H, H2), 7.55 (dd, 1H, H6). 13C NMR
(CD3OD) d: 53.68 (CH), 117.33±134.40 (C Ar), 156.17
(C phenol), 168.68 and 169.84 (COO). The crude pro-
20. Tobias, P.; Kezdy, F. J. J. Amer. Chem. Soc. 1969, 91, 5171.
Â
21. Heathcote, D. M.; De Boos, G. A.; Atherton, J. H.; Page,
M. I. J. Chem. Soc., Perkin Trans. 2 1998, 535.
22. Farrar, C. R.; Williams, A. J. Chem. Soc., Perkin Trans. 2
1979, 1758.
23. Blackburn, G. M.; Dodds, H. L. H. J. Chem. Soc., Perkin
Trans. 2 1974, 377.