1
358
4
. Watson-Clark, R. A.; Banquerigo, M. L.; Shelly, K.; Hawthorne, M. F.; Brahn, E. Proc. Natl. Acad. Sci. USA 1998, 95,
531–2534.
2
5
. Binello, E.; Shefer, R. E.; Yanch, J. C. In Advances in Neutron Capture Therapy; Larsson, B.; Crawford, J.; Weinreich, R.,
Ed.; Elsevier Science: Amsterdam, 1997; I, pp. 459–463. Harling, O. K.; Yanch, J. C.; Choi, J. R.; Solares, G. R.; Rogus, R.
D.; Moulin, D. J.; Johnson, L. S.; Olmez, I.; Wirdzek, S.; Bernard, J. A. Nucl. Sci. Eng. 1992, 110, 330–348.
. Hollander, J. L. Arthritis and Allied Conditions; Hollander, J. L.; McCarty, D. J., Eds.; Lea and Febiger: Philadelphia, 1972;
pp. 517–534. Shaw, J. H.; Knight, C. G.; Thomas, D. P. P.; Phillips, N. C.; Dingle, J. T. Br. J. Exp. Path. 1979, 60, 142–150.
. The synthesis of the acid was based on a personal communication from the research group of Professor Hawthorne, M. F.,
Department of Chemistry and Biochemistry, University of California, Los Angeles, California, USA.
. Kahl, S. B. Tetrahedron Lett. 1990, 11, 1517–1520.
6
7
8
9
. Diago-Meseguer, J.; Palomo-Coll, A. L. Synthesis 1980, 547–551.
1
0. The carborane 3 (591 mg, 2.73 mmol) was dissolved in dichloromethane (50 mL) and BOP-Cl (696 mg, 2.73 mmol)
was added followed by freshly distilled triethylamine (553 mg, 5.47 mmol) and hydrocortisone (1.0 g, 2.76 mmol). The
reaction was stirred at room temperature under nitrogen for 24 h whereupon additional BOP-Cl (348 mg, 1.37 mmol) and
triethylamine (178 mg, 1.36 mmol) were added. The reaction was stirred for an additional 48 h whereupon it was diluted
with dichloromethane (60 mL) and extracted with distilled water (50 mL), 0.1 M HCl (2×50 mL) and 10% NaHCO (2×50
3
mL). The aqueous layers were combined and further extracted with dichloromethane (2×30 mL). The organic layers were
combined and dried over sodium sulfate, filtered, and the solvent evaporated on a rotary evaporator. The resulting yellow
solid was dissolved in a minimum volume of 10% hexanes in dichloromethane and the product (998 mg, 65%) isolated by
silica gel chromatography (CH
2 2 3 2 2 f 3
Cl ). The product showed: TLC (5% CH OH in CH Cl ) R =0.31; MS-NH CI: cluster of
−1
peaks centered around 562 (M+1); IR (nujol, cm ): 3479 (bw, OH), 2923, 2855 (s, CH), 2590 (s, BH), 1721 (s, ester CO),
1
1
655 (s, ketone CO); H NMR (500 MHz, CDCl
3
): δ 5.65 (d, J4,6=1.37 Hz, H-4), 5.14 (AB, J=−17.48 Hz, H-21A), 4.89
0
(AB, H-21B), 4.43 (m, H-11), 3.99 (bs, H-2 ), 2.65 (m, overlap, H-23, 24, 16β), 2.48 (m, H-6), 2.44 (m, H-2β), 2.32 (m,
H-2α), 2.24 (m, H-6α), 2.19 (m, H-1β), 2.10 (m, H-12β), 2.04 (m, H-8), 2.02 (m, H-7β), 1.84 (m, H-1α), 1.77 (m, overlap,
H-14, 15α), 1.71 (m, H-12α), 1.52 (m, H-16α), 1.45 (s, H-18), 1.39 (m, H-15β), 1.11 (m, H-7α), 1.00 (m, H-9α), 0.89
(
(
(
(
s, H-19); 13C NMR (126 MHz, CDCl
C-17), 73.81 (C-1 ), 68.43 (C-21), 67.60 (C-11), 61.34 (C-2 ), 55.79 (C-9), 51.71 (C-14), 47.13 (C-13), 39.42 (C-12), 39.00
C-10), 34.60 (C-1), 33.84 (C-16), 33.57 (C-2), 32.90 (C-23 or 24), 32.60 (C-7), 32.33 (C-23 or C-24), 31.84 (C-6), 31.16
C-8), 23.37 (C-15), 20.71 (C-18), 16.66 (C-19); B NMR (160 MHz, CDCl
12.04, −13.10 (broad, overlap).
3
): δ 205.06 (C-20), 199.26 (C-3), 172.39 (C-5), 170.54 (C-22), 121.83 (C-4), 89.04
0
0
11
3
): δ −2.52 (d), −5.87 (broad), −9.76 (d),
−
1
1. To a flask containing dichloromethane (25 mL) was added 3 (172 mg, 0.793 mmol), BOP-Cl (354 mg, 1.39 mmol), and
triethylamine (276 µL, 2.31 mmol). These reagents were mixed whereupon α-methylprednisolone (349 mg, 0.80 mmol)
was added. The heterogeneous reaction was stirred for 48 h under nitrogen and protected from light. The reaction was
extracted with 0.1 M HCl (2×25 mL) and 10% NaHCO (2×25 mL). The aqueous phases were combined and extracted
3
with dichloromethane (2×20 mL). The organic fractions were combined and dried over sodium sulfate, gravity filtered and
the solvent evaporated. Compound 5 was isolated by radial chromatography (100% EtOAc) followed by recrystallization
−
1
from acetone (300 mg, 66%). The product showed: TLC (100% EtOAc): R =0.58; IR (NaCl, cm ): 3414 (b, OH), 2965,
f
1
2
J
912 (s, CH), 2593 (s, BH), 1727 (ester CO), 1656 (ketone CO); H NMR (500 MHz, CDCl
3
): δ 7.24 (s, H-1), 6.25 (d,
0
1,2=9.8 Hz, H-2), 6.00 (s, H-4), 5.01 (AB, J=−17.5 Hz, H-21A), 4.92 (AB, H-21B), 4.47 (m, H-11), 3.73 (bs, H-2 ), 2.73
(
m, H-16β), 2.64 (m, overlap, H-6, H-23, H-24), 2.20 (m, H-8), 2.07 (m, H-7β), 2.05 (m, H-12β), 1.80 (m, H-15α), 1.66 (m,
H-12α), 1.60 (m, H-14), 1.46 (m, overlap, H-15β, H-16α), 1.43 (s, H-18), 1.10 (d, J6,27=5.50 Hz, H-25), 1.01 (m, H-9), 0.93
13
(
s, H-19), 0.79 (m, H-7α); C NMR (126 MHz, CDCl
3
): δ 204.25 (C-20), 186.69 (C-3), 173.15 (C-5 or C-22), 171.07 (C-5
0
0
or C-22), 156.72 (C-1), 127.53 (C-2), 119.77 (C-4), 89.66 (C-17), 73.76 (C-1 ), 70.11 (C-11), 68.44 (C-21), 61.37 (C-2 ),
5
2
−
5.86 (C-9), 51.36 (C-14), 47.92 (C-13), 44.24 (C-10), 42.92 (C-7), 39.73 (C-12), 34.88 (C-16), 33.11, 33.02, 32.65 (C-6,
1
1
3, 24) 31.10 (C-8), 23.77 (C-15), 21.53 (C-18), 17.73 (C-25), 16.98 (C-19); B NMR (160 MHz, CDCl
3
): δ −2.32 (d),
5.47 (d), −9.31 (d), −11.27, −12.61 (broad, overlap).
1
2. Duddeck, H.; Rosenbaum, D.; Hani, M.; Elgamal, A.; Fayez, M. B. E. Magn. Reson. Chem. 1996, 24, 999–1003. Bhacca,
N. S.; Giannini, D. D.; Jankowski, W. S.; Wolff, M. E. J. Am. Chem. Soc. 1973, 25, 8421–8426.