Four new natural dikctopipcrazine derivatives, cyclouyprostatins A (1). B (2), C (3) and D (4). were isolarcd as new inhibilors of the mammalian cell cycle from lhc secondary mclabolites of Aspergiflus fumigalus BM939 through a separation prc~cdnre guided by ccl1 cycle inhibitory activity. The suucturcs of 1-4 were tirmined by spectroscopic methods cspccially by dctailcd analysts of their lH and l3C NMR spcclra with the aid of 2D NMR techniques. Compounds 1-4 Inhibited the cell cycle progrcwon of tsFl210 cells at the G2/M phase with IC50 values of 5.6 FM (1). 19.5 FM (2). 23.4 FM (3) and 25.3 KM (4), rcspcctivcly. Copyright 0 I996 Elsevier Science Ltd In the course of our screening for new cell cycle inhibitors from microbial origini-?, which might be good candidates for cancer chemotherapy and also be a source for providing molecular probes useful in elucidating regulatory mechanism of the cell cycle, we have previously reported novel diketopiperazine derivatives, tryprostatins2.4.5) A, B and spirotryprostatins 6.71 A, B as well as a new natural diketopiperazine derivative, demethoxyfumitremorgin C4.5), together with four known diketopiperazines'J), fumitremorgin C, 12,13dihydroxyfumitremorgin C, fumitremorgin B and vertuculogen, as a new group of G2/M-phase inhibitors of the mammalian cell cycle, which were isolated from the fermentation broth of a fungus, Aspergillusfumigaru BM9392-7). In the continuation of that work, we have recently isolated four new natural diketopiperazine derivatives, cyclottyprostatins A (l), B (2), C (3) and D (4) (Chart l), from the fermentation broth of Aspergillus futnigatus BM939 through a separation procedure guided by inhibitory activity on the cell cycle progression of 1: R=H 2: R=CHs Chart 1 Structures of Cyclotryprostatins A (I), B (2), C 3 4
(3) and D (4).