Van Maarseveen J H, Hermkens P H, De Clercq E, Balzarini J, Scheeren H W, Kruse C G
Department of Organic Chemistry, University of Nijmegen, The Netherlands.
J Med Chem. 1992 Aug 21;35(17):3223-30. doi: 10.1021/jm00095a019.
The in vitro antiviral and antitumor activities of (-)-debromoeudistomin K (1a) and 10 structural analogues (1b-1j and 11) were evaluated. The synthesis was accomplished with an intramolecular Pictet-Spengler condensation reaction as the key step. This examination revealed some structural and stereochemical features that are important for both the antiviral and antitumor activities. The most striking points for activity are the necessity to have the correct natural stereochemistry at both C(1) and C(13b) and the presence of the C(1)-NH2 substituent. As was revealed before with naturally isolated eudistomins a substituent in the indole ring greatly influences the biological activity. The 5-OMe derivative 1h shows high potency in both antiviral and antitumor models.
评估了(-)-去溴优地斯明K（1a）和10种结构类似物（1b - 1j和11）的体外抗病毒和抗肿瘤活性。合成以分子内Pictet - Spengler缩合反应为关键步骤完成。该研究揭示了一些对抗病毒和抗肿瘤活性都很重要的结构和立体化学特征。活性最显著的要点是在C(1)和C(13b)处都具有正确的天然立体化学以及C(1)-NH2取代基的存在。正如之前对天然分离的优地斯明所揭示的那样，吲哚环中的取代基对生物活性有很大影响。5 - OMe衍生物1h在抗病毒和抗肿瘤模型中均显示出高效力。
