COMMUNICATIONS
2000, 103, 467), confirmed the pharmacophore analysis reported in
[6a, b].
[7] a) H. C. Kolb, B. Ernst, Chem. Eur. J. 1997, 1571; b) W. Jahnke, H. C.
Kolb, M. J. J. Blommers, J. L. Magnani, B. Ernst, Angew. Chem. 1997,
109, 2715; Angew. Chem. Int. Ed. Engl. 1997, 36, 2603; c) H. C. Kolb,
B. Ernst, Pure Appl. Chem. 1997, 69, 1879.
Hensley, P. J. McDevitt, I. Brooks, J. J. Trill, J. A. Feild, D. E. McNulty,
J. R. Connor, D. E. Griswold, N. V. Kumar, K. D. Kopple, S. A. Carr,
B. J. Dalton, K. Johanson, J. Biol. Chem. 1994, 269, 23949; d) R.
Harris, G. R. Kiddle, R. A. Field, B. Ernst, J. L. Magnani, S. W.
Homans, J. Am. Chem. Soc. 1999, 121, 2546.
[22] The H2G ± H5F NOE value decreases in the bound state, not only for
antagonist 2, but also for sLex.[21] This effect can be readily interpreted
as a lateral translation of fucose relative to galactose in the direction of
more negative (f,y) values, which accompanies the relative approach
of fucose and galactose upon binding.
[23] a) A. Fersht in Enzyme Structure and Mechanism, 2nd ed., Freeman,
New York, 1985; b) M. S. L. Lim, E. R. Johnston, C. A. Kettner, J.
Med. Chem. 1993, 36, 1831; c) D. G. Alberg, S. L. Schreiber, Science
1993, 262, 248; d) H. Kessler, Angew. Chem. 1982, 94, 509; Angew.
Chem. Int. Ed. Engl. 1982, 21, 512.
[8] G. Thoma, W. Kinzy, C. Bruns, J. T. Patton, J. L. Magnani, R. Bänteli,
J. Med. Chem. 1999, 42, 4909.
[9] Individual protein ± carbohydrate interactions are generally weak
(KD 10 3 ± 10 4 m) and cannot readily be greatly improved. a) Y. C.
Lee, R. T. Lee, Acc. Chem. Res. 1995, 28, 321; b) G. S. Jacob, C.
Kirmaier, S. Z. Abbas, S. C. Howard, C. N. Steininger, J. K. Welpley, P.
Sudder, Biochemistry 1995, 34, 1210; c) M. Mammen, S.-K. Choi,
G. M. Whitesides, Angew. Chem. 1998, 110, 2908; Angew. Chem. Int.
Ed. 1998, 37, 2754.
[10] A series of compounds with different R groups, such as aliphatic and
aromatic amides, carbamates, sulfonamides, and ureas, has been tested
and all of the compounds showed very similar affinities to E-selectin.
Compounds 3b ± d were selected as representative examples. See: R.
Bänteli, P. Herold, C. Bruns, J. T. Patton, J. L. Magnani, G. Thoma,
Helv. Chim. Acta 2000, 83, 2893.
1
[11] Compound 4: H NMR (600 MHz, D2O, 25 8C, DSS): d 5.03 (H1F),
3.78 (H2F), 3.88 (H3F), 3.80 (H4F), 4.77 (H5F), 1.19 (H6F), 4.49 (H1G),
3.60 (H2G), 3.38 (H3G), 3.89 (H4G), 3.60 (H5G), 3.72 (H6G), 3.47
(H1aS), 3.94 (H1eS), 1.62 (H2aS), 2.21 (H2eS), 3.98 (H3S), 3.27 (H4S),
3.43 (H5S), 1.35 (H6S). Compound 5: 1H NMR (600 MHz, D2O, 25 8C,
DSS): d 4.96 (H1F), 3.74 (H2F), 3.88 (H3F), 3.79 (H4F), 4.42 (H5F),
1.19 (H6F), 4.49 (H1G), 3.58 (H2G), 3.38 (H3G), 3.90 (H4G), 3.62 (H5G),
3.72 (H6G), 3.55 (H1aS), 3.90 (H1eS), 1.67 (H2aS), 2.15 (H2eS), 4.01
(H3S), 3.66 (H4S), 3.46 (H5aS), 3.99 (H5eS). Compound 6: 1H NMR
(600 MHz, D2O, 25 8C, DSS): d 4.91 (H1F), 3.76 (H2F), 3.87 (H3F),
3.78 (H4F), 4.12 (H5F), 1.20 (H6F), 4.44 (H1G), 3.59 (H2G), 3.40 (H3G),
3.91 (H4G), 3.66 (H5G), 3.75 (H6G), 3.88, 3.70 (H1S), 4.08, 3.86 (H2S).
F fucose, G galactose, S spacer between F and G.
Benzene-Free Synthesis of Phenol**
James M. Gibson, Phillip S. Thomas, Joshua D. Thomas,
Jessica L. Barker, Sunil S. Chandran, Mason K. Harrup,
Karen M. Draths, and John W. Frost*
Although phenol has been synthesized by a succession of
processes, the Hock oxidation of benzene-derived cumene
(Scheme 1) is currently the predominant method used in the
[12] a) H. C. Kolb, WO 9701569, 1997; b) T. Ogawa, Y. Ito, S. Sato, Y.
Morisawa, JP 63051396, 1998.
[13] U. Spohr, M. Bach, R. G. Spiro, Can. J. Chem. 1993, 71, 1919.
[14] F. Yamazaki, T. Kitajima, T. Numata, T. Ito, T. Ogawa, Carbohydr.
Res. 1990, 201, 15.
[15] D. H. R. Barton, J. C. Jaszberenyi, Tetrahedron Lett. 1989, 30, 2619.
[16] S. Bouhroum, J. A. Grondin, S. Houdier, H. Lazrek, M. Rhazi, A.
Tolaimate, P. J. A. Vottero, J. Carbohydr. Chem. 1991, 10, 309.
[17] S. Rio, J. M. Beau, J. C. Jacquinet, Carbohydr. Res. 1991, 219, 71.
[18] G. Thoma, J. L. Magnani, R. Oehrlein, B. Ernst, F. Schwarzenbach,
R. O. Duthaler, J. Am. Chem. Soc. 1997, 119, 7414.
[19] a) G. Thoma, R. O. Duthaler, B. Ernst, J. L. Magnani, J. T. Patton, WO
9719105, 1997; b) G. Thoma, J. T. Patton, J. L. Magnani, B. Ernst, R.
Oehrlein, R. O. Duthaler, J. Am. Chem. Soc. 1999, 121, 5919.
[20] NMR spectroscopic measurements were carried out on a Varian
UnityPlus 600 spectrometer operating at a frequency of 600 MHz. All
experiments were carried out at 258C with compound concentrations
of approximately 10 mm in D2O solutions. ROESY experiments were
carried out with mixing times of 150 ms. For some compounds,
ROESY spectra were recorded using 50 ms and 100 ms mixing times,
and the results were indistinguishable. Typical acquisition times in the
direct and indirect dimensions were 340 ms and 64 ms, respectively.
The data were zero-filled to yield a digital resolution of 1.46 Hz and
2.92 Hz, respectively. For bound 2, NOE values were extracted from
transfer NOE spectra (see ref. [7b]). Signal integration was performed
using Varian VNMR software. All NOEs were normalized using
intraglycosidic NOE enhancements such as H1G ± H3G and H4F ± H5F.
The distances between these hydrogens are given by the chair
conformations of fucose and galactose and should be very similar
for compounds 2, 4, 5, and 6. It should be noted that the measured
NOE values do not refer to a distinct conformation of the molecule
but represent the weighted mean distance over several coexisting low
energy conformations.
Scheme 1. Synthesis of phenol. Conditions: a) E. coli SP1.1PTS /
pSC6.090B; b) 1) H2O, 3508C, 2) Cu0, H2O, 3508C; c) propene, AlCl3;
~
d) 1. O2, 1008C, 2. , H2SO4.
production of phenol, which amounts to 5 Â 109 kg annually.[1]
Most of the past and currently employed phenol syntheses use
benzene,[1] a volatile organic carcinogen, as the starting
[*] Prof. J. W. Frost, Dr. J. L. Barker, Dr. S. S. Chandran,
Dr. M. K. Harrup, Prof. K. M. Draths
Departments of Chemistry and Chemical Engineering
Michigan State University
East Lansing, MI 48824 (USA)
Fax : (1)517432-3873
Prof. J. M. Gibson, P. S. Thomas, J. D. Thomas
Chemistry Department, Wingate University
Wingate, NC 28174 (USA)
Fax : (1)704-233-8233
[**] This research was supported by
Department of Agriculture.
[21] a) K. Scheffler, B. Ernst, A. Katopodis, J. L. Magnani, W. T. Wong, R.
Weisemann, T. Peters, Angew. Chem. 1995, 107, 2034; Angew. Chem.
Int. Ed. Engl. 1995, 34, 1841. For the investigation of the bioactive
conformation of sLex, see also: b) R. M. Cooke, R. S. Hale, S. G.
Lister, G. Shah, M. P. Weir, Biochemistry 1994, 33, 10591; c) P.
a grant awarded by the U.S.
Supporting information for this article is available on the WWW under
Angew. Chem. Int. Ed. 2001, 40, No. 10
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
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