Isolation and Structure of Bryostatin 1

Journal of the American Chemical Society

Volumn 104, Issue 24, 1982, Pages 6846-6848

  Pettit, George R ^a   Herald, Cherry L ^a   Doubek, Dennis L ^a   Herald, Delbert L ^a   Arnold, Edward ^b   Clardy, Jon ^b  

^a ARIZONA STATE UNIVERSITY   (United States)

^b Cornell University ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BRYOSTATIN 1; NEW DRUG;

BLOOD AND HEMOPOIETIC SYSTEM; CRYSTALLOGRAPHY; DRUG ANALYSIS; DRUG CYTOTOXICITY; DRUG IDENTIFICATION; DRUG ISOLATION; DRUG SCREENING; DRUG STRUCTURE; IN VITRO STUDY; INFRARED SPECTROMETRY; INTOXICATION; INVERTEBRATE; LEUKEMIA P 388; MASS SPECTROMETRY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PRELIMINARY COMMUNICATION; THIN LAYER CHROMATOGRAPHY; ULTRAVIOLET SPECTROPHOTOMETRY;

EID: 0020408957     PISSN: 00027863     EISSN: 15205126     Source Type: Journal    
DOI: 10.1021/ja00388a092     Document Type: Article

References (25)

1. Contribution 86 of the series “Antineoplastic Agents”; for part 85 refer to: Pettit, G. R.; Paull, K. D.; Herald, C. L.; Herald, D. L.; Riden, J. R., submitted for publication in Can. J. Chem.
2. Woollacott, R. M., Zimmer, R. L., Eds., “Biology of Bryozoans”; Academic Press: New York, 1977.
3. Day, J. H. “A Guide to Marine Life on South African Shores”; Balkema: Cape Town, 1974; p 123. One type (avicularium) of Bugula neritina L. polypide resembles the beak of a bird and by closing one jaw against the other is able to protect the colony from uninvited encroachment. Such avicularia are a common component of B. neritina L.
4. Benson, P. H.; Moncreiff, R. W. C. R. Congr. Int. Corros. Mar. Salissures, 4th 1977.
5. Pettit, G. R.; Day, J. F.; Hartwell, J. L.; Wood, H. B. Nature (London) 1970, 227, 962–963.
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9. Wulff, P., Carlé, J. S.; Christophersen, C. J. Chem. Soc., Perkin Trans. 1 1981, 2895;
10. Comp. Biochem. Physiol. B 1982, 71B, 525, 523.
11. Of the presently known cyclic ionophores only the Streptomyces griseus component aplasmomycin seems distantly related to bryostatin 1: Okami, Y.; Okazaki, T.; Kitahara, T.; Umezawa, H. J. Antibiot. 1976, 29, 1019.
12. Nakamura, H.; Iitaka, Y.; Kitahara, T.; Okazaki, T.; Okami, Y. J. Antibiot. 1977, 30, 714.
13. Schmidt, J. M.; Pettit, G. R. Experientia 1978, 34, 659–660.
14. Pettit, G. R.; Ode, R. H. “Biosynthetic Products for Cancer Chemotherapy”; Plenum Press: New York, 1979; Vol. 3, p 59.
15. Pettit, G. R.; Herald, C. L.; Kamano, Y.; Gust, D.; Aoyagi, R. J. Nat. Prod., in press.
16. A similar type of transformation has been observed for the hydrochloride of gramicidin S: Hodgkin, D. C.; Oughton, B. M. Biochem. J. 1957, 65, 752–756.
17. All crystallographic calculations were done on a Prime 850 computer, operated by the Cornell Chemistry Computing Facility. Principal programs employed were REDUCE and UNIQUE, data reduction programs: Leonowicz, M. E., Cornell University, 1978.
18. MULTAN 78, “A System of Computer Programs for the Automatic Solution of Crystal Structures from X-ray Diffraction Data”, direct methods programs and fast Fourier transformation routine (locally modified to perform all Fourier calculations including Patterson syntheses): Main, P.; Hull, S. E.; Lessinger, L.; Germain, G.; Declercq, J.-P.; Woolfson, M. M., University of York, England, 1978.
19. NQEST, CYBER 173 version, negative quartets figure of merit calculation: Weeks, C. M., Medical Foundation of Buffalo, Inc., August 1976.
20. BLSA, anisotropic block-diagonal least-squares refinement: Hirotsu, K.; Arnold, E., Cornell University, 1980.
21. ORTEP, crystallographic illustration program: Johnson, C. K., Oak Ridge, TN, ORNL-3794, June, 1965.
22. Karle, J. Acta Crystallogr., Sect. B 1968, B24, 182–186.
23. Main, P. Acta Crystallogr., Sect. A 1979, A35, 779–785.
24. For more detail see: Arnold, E. Ph.D. Dissertation, Cornell University, Ithaca, NY, 1982.
25. The enantiomer of bryostatin 1 shown in Figure 1 was selected as follows: The method of Engel (Engel, D. W. Acta Crystallogr., Sect. B 1972, B28, 1498–1509) was used to measure anomalous scattering effects due to oxygen and carbon (Δf″ = 0.032 and Δf″= 0.009 electrons, respectively, for Cu Kα radiation). Seven groups of Bijvoet pairs that were expected to have the largest Bijvoet ratios were measured (three times) very slowly by using Cu Kα radiation and the same crystal that had been used for the Mo Kα data collection. Neighboring pairs, which in each case were centrosymmetric reflections, were measured in a manner similar to provide an empirical correction for absorption and other anisotropic effects. The absorption-corrected Bijvoet ratios that were obtained for each of the seven groups indicated the enantiomer shown in Figure 1. Efforts to determine the absolute configuration of bryostatin 1 are continuing.