The first colchicine analogue with an eight membered B-ring. Structure, optical resolution and inhibition of microtubule assembly

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 21, 1997, Pages 2771-2776

  Berg, Ulf ^a   Bladh, Håkan ^a   Svensson, Christer ^a   Wallin, Margareta ^b  

^a LUND UNIVERSITY   (Sweden)

^b UNIVERSITY OF GOTHENBURG   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

COLCHICINE DERIVATIVE;

ANIMAL CELL; ARTICLE; CIRCULAR DICHROISM; CRYSTAL STRUCTURE; DRUG ACTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; MICROTUBULE ASSEMBLY; NONHUMAN; STEREOCHEMISTRY;

EID: 0030785167     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)10070-1     Document Type: Article

References (14)

1. This is Part 3 in the series: Stereochemical Variations on the Colchicine Motif. Part 2: see ref. 3b.
2. a) Capraro, H.-G.; Brossi, A. "Tropolonic Colchicum Alkaloids", In The Alkaloids, Ed A. Brossi, Academic, New York, 1984, 23, 1-70;
3. b) Boyé, O.; Brossi, A. "TropolonicColchicum Alkaloids", In The Alkaloids, Ed. A. Brossi, Academic, New York, 1992, 41, 125-176;
4. c) Bane Hastie, S. Pharmac. Ther., 1991, 51, 377-401.
5. a) Berg, U.; Deinum, J.; Lincoln, P.; Kvassman, J. Bioorg. Chem., 1991, 19, 53-65;
6. b) Berg, U.; Bladh, H.; Hoff, M.; Svensson, C. J. Chem. Soc., Perkin Transaction 2, in print.
7. Detrich, III, H. W.; Williams, Jr., R. C.; Macdonald, T. L.; Wilson, L.; Puett, D. Biochemistry, 1981, 21, 5999-6005.
8. Hastie, S. B.; Rava, R. P. J. Am. Chem. Soc., 1989, 111, 6993-7001.
9. Lincoln, P.; Nordh, J.; Deinum, J.; Ångström, J.; Nordén, B. Biochemistry, 1991, 30, 1179-1187.
10. Shi, Q.; Verdier-Pinard, P.; Brossi, A.; Hamel, E.; McPhail, A. T.; Lee, K.-H. J. Med. Chem. 1997, 40, 961-966.
11. 5S calcd for 387.1140 found 387.1137.
12. max = 50° at 25 °C. Some selected bond lengths (Å) and bond angles(°): S1-C10 1.741(6), S1-C16 1.787(6), O1-C1 1.377(6), O1-C13 1.401(8), O2-C2 1.377(6), O2-C14 1.413(7), O3-C3 1.374(6), O3-C15 1.421(7), O4-C7 1.227(7), O5-C9 1.226(7), Cla-Cl 1.399(7), Cla-C4a 1.404(7), Cla-C12a 1.494(7), C6-N1 1.450(7), N1-C7 1.330(7), C7a-C7 1.514(8), C7a-C8 1.356(7), C7a-C12a 1.430(8), C8-C9 1.439(7), C9-C10 1.465(8), C10-C11 1.366(7), C11-C12 1.428(8), C12a-C12 1.370(8), C10-S1-C 16 104.0(3), C4a-C5-C6 115.9(3), C1-O1-C13 114.5(5), C5-C6-N1 115.1(5), C6-N1-C7 124.9(6), C2-O2-C14 116.3(5), C3-O3-C15 118.3(5), C8-C7a-C12a 129.9(5), N1-C7C7a 115.3(5), C7a-C8-C9 133.7(6), C8-C9-C10 122.2(6), C9-C10-C11 127.7(5), C10-C11-C12 130.5(6), C7a-C12a-C12 123.4(5), Cll-C12-C12a 131.6(6). The structure was solved by direct methods (SIR-92), and refined on F using the teXsan programme package. All non-hydrogen atoms were refined with anisotropic thermal parameters. Hydrogen atoms were included at calculated positions with fixed isotropic thermal parameters, except for the amino hydrogen, which was refined isotropically. R = 0.053, wR = 0.056, S = 1.19 for 2017 observed data, I>3 σ(I). Crystallographic data (excluding structure factors) for the stucture reported in this paper have been deposited with the Cambridge Crystallographic Data Centre. Copies of the data can be obtained free of charge on application to The Director, CCDC,12 Union Road, Cambridge CB2 1EZ UK (fax: Int. Code +(1223) 336-033; e-mail: deposit@chemcrys.cam.ac.uk). Cambridge Structural Database, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, England.
13. Equipment according to: Isaksson, R.; Roschester, J. J. Org. Chem., 1985, 50, 2519-2521. The eluate was analyzed by both UV (254 nm) and polarimeter (436 nm).
14. Preparation of bovine brain tubulin and microtubule associated proteins and turbidity measurements were performed according to: de Pereda, J. M; Wallin, M.; Billger, M.; Andreu, J. M. Cell Motil. Cytoskeleton, 1995, 30, 153-163.