Progress in the Chemistry of Organic Natural Products
- PDF / 3,361,040 Bytes
- 80 Pages / 430.866 x 649.134 pts Page_size
- 91 Downloads / 233 Views
Research, Bayer HealthCare AG, Wuppertal, Gennany* Chemistry, Schering AG, Berlin, Gennany* 3 Central Research, Bayer Chemicals AG, Leverkusen, Gennany* 4Institut fiir Organische Chemie der Universitiit Hannover, Hannover, Gennany 2 Medicinal
Contents 1. Introduction 2. Synthesis of Bissteroidal Pyrazines ............................. 2.1. Synthesis of Symmetrical Pyrazines and Subsequent Desymmetrization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Directed Synthesis of Unsymmetrical Pyrazines ................. 2.2.1. Nonacyclic Cephalostatin Analogues .................... 2.2.2. Dienes .........................................
15 16 28 37 39
3. A-D-Ring Functionalization .................................. 3.1. Introduction of the Steroidal .6,14.15 -Bond ..................... 3.2. Chemical Modifications on the .6,14,15_ Double Bond .............
42 44 56
4. The Spiroketal Area of CephaJostatins . . . . . . . . . . . . . . . . . . . . . . . . . . .
60
5. Summary ...............................................
70
Acknowledgements ..........................................
74
References ................................................
75
1. Introduction The cephalostatin field started off with the seminal publication of Pettit et ai. in 1988 describing structure and biological activity of cephalostatin 1 (1) (84). Since then several reviews have covered the activities regarding isolation, structure elucidation, biological activities, and synthetic efforts up to 1995 (1, 2, 34-36, 54, 111). This account will focus on the synthesis and biological activity of cephalostatin analogues as published until early 2002. The authors understand the *Current address.
H. Budzikiewicz et al., Progress in the Chemistry of Organic Natural Products © Springer-Verlag/Wien 2004
2
T. Flessner et al.
purpose of this review to provide a complete overview of the cephalostatinJritterazine analogue field. However, this article will in parts be biased to describe some work of the Winterfeldt group in more detail, based on the personal experience of the authors. Natural products from a wide variety of sources have always played an important role in medical treatment. Either these compounds or their derivatives are employed as drugs or as starting points for diverging drug discovery programs or as tools to investigate and elucidate novel targets for the treatment of diseases. In this respect at least one third of the currently available drugs are based on natural products or close derivatives and numerous prominent "synthetic drugs" would have not been found without natural products leading the way. In 1955, the National Cancer Institute (NCI) started a large program aimed at identifying novel compounds possessing anti-tumor effects. Based on the excellent track record of natural products, a substantial part of these efforts was directed towards natural products and only from 1955 to 1980 approximately 130000 extracts from plants and animals were examined. In 1974 extracts originating from t
Data Loading...
