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the antibody. We have prepared a series of taxanes in
which a simple disulfide bond has been incorporated at
various positions. This positional scanning approach
has identified that both the C-7 and C-10 positions are
most suitable for this endeavor. Using the C-10 position
to maintain the disulfide, we also prepared a series of C-
2 modified taxanes. This led to the development of
‘linkable’ taxanes with exceptional potency (17a,c,d).
These taxanes have the desired potency needed and can
be coupled to an antibody for evaluation as immuno-
conjugates. The preparation and pre-clinical evaluation
of these immunoconjugates will be reported in due
course.
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Acknowledgements
This work was supported in part by a grant from the
National Institutes of Health (GM 427980 to I.O.)
17. Kingston, D. G. I.; Chaudhary, A. G.; Chordia, M. G.;
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19. Experimental data example for taxoid 17a: 1H NMR
(CDCl3) d 1.15 (s, 3H), 1.26 (s, 3H), 1.35 (s, 9H), 1.68 (s,
3H), 1.75 (s, 3H), 1.76 (s, 3H), 1.85 (m, 1H), 1.88 (m, 1H),
1.91 (s, 3H), 2.32 (m, 1H), 2.37 (s, 3H), 2.43 (s, 3H), 2.57
(m, 1H), 3.00 (m, 4H), 3.82 (d, J ¼ 7:2 Hz, 1H), 4.16 (d,
J ¼ 8:4 Hz, 1H), 4.20 (d, J ¼ 2:4 Hz, 1H), 4.30 (d,
J ¼ 8:4 Hz, 1H), 4.42 (dd, J ¼ 6:8, 10.8 Hz, 1H), 4.74
(m, 2H), 4.98 (d, J ¼ 8:0 Hz, 1H), 5.32 (br s, 1H), 5.62 (d,
J ¼ 7:2 Hz, 1H), 6.15 (t, J ¼ 8:8 Hz, 1H), 6.34 (s, 1H), 7.43
(t, J ¼ 7:6 Hz, 1H), 7.59 (d, J ¼ 7:6 Hz, 1H), 7.99 (d,
J ¼ 7:6 Hz, 1H), 8.12 (s, 1H). 13C NMR (CDCl3) d 9.5,
15.0, 16.6, 22.3, 23.2, 25.7, 26.6, 28.0, 32.1, 34.2, 35.5, 35.6,
43.1, 45.6, 51.6, 58.5, 72.2, 72.3, 73.7, 75.4, 75.8, 76.3, 79.3,
81.0, 84.4, 116.5, 120.5, 128.4, 130.0, 130.2, 131.0, 132.5,
133.7, 134.8, 143.0, 152.1, 155.4, 165.6, 170.0, 172.1, 203.5.
HRMS (FAB): m=z HRMS for C45H60ClNO15S2Naþ:
calcd: 976.2991; found: 976.2984 (D ¼ 0:7 ppm).
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