THE STEREOSELECTIVITY OF ANTITUMOR ACTIVE [1,2-DIAMINO-1-PHENYLPROPANE]DICHLOROPLATINUM(II) COMPLEXES

The syntheses of enantiomeric threo- and erythro-1,2-diamino-1-phenylp ropanes (Ph/Me) and of the racemic 1,2-diaminophenylethane (Ph/H) are described. These diamines and related N-2-methyl- and N-1,N-2-dimethyl -l,2-diamino-1-phenylpropanes were transformed into dichloroplatinum(I I) complexes (Ph/H-PtCl2, Ph/Me-PtCl2, Ph/Me-Me-PtCl2, Ph/Me-Dime-PtCl 2). For the H-1 NMR spectroscopical determination of their optical pur ity the diamines (Ph/Me) were converted with (R)-myrtenal into their d iimines. In the test on the MCF-7 breast cancer cell line (R,R)-Ph/Me- PtCl2 produced the strongest effect of all new complexes, comparable w ith that of the standard cisplatin and of other Pt complexes. Its enan tiomer (S,S)-Ph/Me-PtCl2 possessed a distinctly weaker inhibitory pote ncy while the erythro-configurated counterparts were even less active [(R,R) > (S,S) > (S,R) = (R,S)]. All N-2-methylated and N-1,N-2-dimeth ylated complexes (Ph/Me-Me-PtCl2, Ph/Me-Dime-PtCl2) showed comparable activities equaling those of (R,S)- and (S,R)-Ph/Me-PtCl2. The molecul ar reasons for the differing potencies of the diastereomeric and enant iomeric Ph/Me-PtCl2 complexes are discussed in consideration of the co mplex conformation. (C) 1997 Elsevier Science S.A.