@article {4194, title = {Granulatimide and isogranulatimide, aromatic alkaloids with G2 checkpoint inhibition activity isolated from the Brazilian ascidian Didemnum granulatum: Structure elucidation and synthesis}, journal = {Journal of Organic Chemistry}, volume = {63}, number = {26}, year = {1998}, note = {ISI Document Delivery No.: 153LPTimes Cited: 72Cited Reference Count: 34}, month = {Dec}, pages = {9850-9856}, type = {Article}, abstract = {Crude methanol ex-tracts of the ascidian Didemum granulatum collected in Brazil showed activity in a new screen for G2 cell cycle checkpoint inhibitors. Bioassay-guided fractionation of the extract yielded the known alkaloids didemnimides A (1) and D (2), the new alkaloid didemnimide E (3), and a new G2 checkpoint inhibitor. Two candidate structures for the inhibitor, named granulatimide (4) and isogranulatimide (5), have been prepared via a short and efficient biomimetic synthesis involving the photolysis of didemnimide A (1). The synthesis revealed that the correct structure for the naturally occurring G2 checkpoint inhibitor is isogranulatimide (5). Granulatimide (4), the other candidate structure, was also found to be a G2 checkpoint inhibitor, and it was subsequently detected in chromatographic fractions associated with purification of D. granulatum alkaloids. Granulatimide (4) and isogranulatimide (5) represent the first examples of a new class of G2 specific cell cycle checkpoint inhibitors and the first ones identified through a rational screening program.}, keywords = {BHK CELLS, CAFFEINE, CELL-CYCLE CHECKPOINTS, DNA-REPLICATION, HELA-CELLS, INDUCED G(2) DELAY, mitosis, PROTEIN-KINASE, RADIOSENSITIZATION, STAUROSPORINE}, isbn = {0022-3263}, url = {://000077834800044}, author = {Berlinck, R. G. S. and Britton, R. and Piers, E. and Lim, L. and Roberge, M. and da Rocha, R. M. and Andersen, R. J.} }