Spectral and Analytical Characterization

The crystal structure determination (77) of bryostatin 1 in 1982 and the interpretation (29) of the corresponding high field (400 MHz) NMR spectra formed the basis for all subsequent bryostatin structure determinations. All 400 MHz H-NMR spectra of the bryostatins until about 1986 were measured using an early model of the Bruker 400 instrument and required coupling assignments by hand. Hence some minor adjustments in the early proton assignments have already been found necessary. 

As illustrations. Tables 2 and 3 list assignments for the H-NMR spectra of two important bryostatins and two bryostatin acetates while Fig. 5 lists assignments for the C-NMR spectrum of bryostatin 12. Fig. 6 shows the ultraviolet spectra, while mention of other ultraviolet, infrared, and mass spectral characteristics has already been made in Section 5. However an illustration of the application of mass spectrometry to the structure elucidation of bryostatins 5-7 will be instructive (27). The solution phase secondary ion mass spectra of these three bryostatins were quite revealing when new techniques for detecting molecular ions of hitherto refractory substances were utilized. By employing an alkali metal iodide such as sodium iodide or silver tetrafluoro-borate or thallium tetrafluoroborate in sulfolane the molecular ions 

More recently it has been found (unpublished experiments) in the laboratories of Dr. Peter Blumberg (NCI) that bryostatins 1 and 2 will afford PS ED50 values in the 10pg/ml range if the leukemia cells are exposed to only that concentration range. In other words the cytostatic activity of the bryostatins markedly increases as their concentration 

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