Staurosporine, 7-hydroxy

The UV 242, 291, 320, 334, 354, and 370 nm) and IR 1670 and 3400 cm ) spectra of 4 -N-methyl-5 -hydroxystaurosporine (300) were very similar to those of (+)-staurosporine (295) (see Scheme 2.74), indicating the presence of a similar indolo[2,3-fl]carbazole framework with a lactam function. The NMR spectra of 4 -N-methyl-5 -hydroxystaurosporine (300) were also very similar to those of (+)-staurosporine (295) (see Scheme 2.74), except for the difference in the substitution pattern of the sugar moiety. Thus, the H-NMR spectrum showed two shielded N-methyl singlets at 2.37 and a doublet (/=9.9Hz) for the C-5 proton at 4.43 and the C-3 singlet at 5 3.95, and a shielded doublet (/=9.9 Hz) for the C-4 proton at 5 3.02, indicating the presence of additional methyl and hydroxy groups at the C-4 N-methyl and the C-5 carbon, respectively. Based on these spectral data, and the structural similarity to (+)-staurosporine (295), the structure 300 was assigned to 4 -N-methyl-5 -hydroxystaurosporine. This structure was further supported by the C-NMR and NOESY spectra (298) (Scheme 2.75). 

The potent protein kinase inhibitor staurosporine (121) was first isolated in 1977 from the actinomycete strain AM-2282 [133], which was later reclassified as Lentzea albida [134]. Staurosporine (121) has received immense attention as a potential chemotherapeutic, possessing nanomolar inhibitory activity against protein kinase C (PKC) [135]. Its inhibitory activity against multiple protein kinases in cells has prompted an investigation of related molecules with less potent, but more PKC-specific, activity [12, 136]. A related molecule, UCN-01 or 7-hydroxy-staurosporine (122), differing from staurosporine (121) only in the presence of a... 

To complete the total S3mthesis of ent-staurosporine (2), a two-step deprotection strategy (hydrogenation followed by aminal hydrolysis) delivered 64 from 63 in high yield (Scheme 8). Danishefsky et al. preferred to clarify the monosaccharide domain prior to reducing the maleimide function [45], The most efficient method involved reduction of the imide group with sodium borohydride to provide a mixture of hydroxy lactams. Further reduction... 

Many other alkaloids have been isolated from polydtorid ascidians, and we will present only some of the most important structures. Among these, it is worth mentioning two hydroxy derivatives of staurosporine and rigidins A-E, which form a group of pyrrolopyrimidine derivatives. Some of them are calmodulin antagonists. These derivatives were isolated from species of the genera Cystodytes and Eudistoma. 

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