We describe an improved synthetic strategy for the preparation of nucleic acid encoded peptide and protein libraries. A solid-phase format was used to prepare and purify a novel type of mRNA-template for in vitro mRNA-protein fusion synthesis. The present protocol simplifies and accelerates the preparation of fusion libraries and should prove most useful for in vitro protein evolution procedures which involve repetitive cycles of fusion library preparation and selection.

Combinatorial chemistry, combined with recent advances in robotic screening, which enable the testing of a large number of compounds in a short period of time, is becoming an important tool in accelerating drug discovery. This technique involves the preparation of a large number of structurally related compounds either as mixtures in the same reaction vessel or individually by parallel synthesis. In this manner large pools of similar compounds can be synthesized within a short period of time. Combinatorial libraries have been prepared using both solution chemistry and by solid phase synthesis; however, solid phase synthesis allows the use of excess reagents to drive the reaction to completion and easy removal of the reagents and side-products by simple filtration of the polymeric support and washing with solvent. Therefore, solid phase synthesis offers a more attractive approach to the generation of chemical libraries for screening purposes.

According to the toxin hypothesis, reactive chemical compounds (e.g. alkanes, carbolines, cyanides, isoquinolines, heavy metals, pesticides) arising from environmental pollution or drug abuse are discussed to be causative factors for the induction of neurodegenerative processes, e.g. Parkinson's disease.

The significance of rodent damage to health, agricultural production or structures has come to be widely recognised as economically very important (1). Plants offer an excellent source of biologically active natural products. The most important botanical rodenticides are scilliroside (2), reserpine (3) and strychnine (4). The natural products used as rodenticides per se are all acute poisons until the discovery of the anticoagulant rodenticides in the early 1950s (4). The spread of rat resistance to anticoagulant rodenticides limited the effectiveness of rat control (5). Therefore, and beside resistance management (6), the development of new natural products, to be directly used or as lead for synthesis, will be the most practicable method to solve most rat problems.

In our on-going programs aimed to the discovery of new pesticides of plant origin, we have extensively studied the composition in secondary metabolites of various indigenous plants from the Sudan, known for their promising biological activity and sometimes even used in traditional agriculture for pest management purposes.

The role of plant secondary metabolites in host plant recognition, especially in oligophagous insects, is of great importance. Substances eliciting feeding responses of the insects have been extensively studied and numerous attempts have also been made in the past decades to isolate antifeedants from plants avoided by insect species. As the most studied of these plant secondary metabolites with antifeedant activity, but also in some cases insecticide activity, one should cite polygodial 1 1, waburganal 2 2, azadirachtine3 , toosendanine 4 4, clerodanes 5 (clerodine 5) and ecdysteroids 6 (20-hydroxyecdysone 6). However, the diversity of structure of these products, the diversity of their biological activities and their structural complexity did not allow establishment of unambiguous structure-antifeedant activity relationships.

The role of plant secondary metabolites in host plant recognition, especially in oligophagous insects, is of great importance. Substances eliciting feeding responses of the insects have been extensively studied and numerous attempts have also been made in the past decades to isolate antifeedants from plants avoided by insect species. As the most studied of these plant secondary metabolites with antifeedant activity, but also in some cases insecticide activity, one should cite polygodial 1 1, waburganal 2 2, azadirachtine3 , toosendanine 4 4, clerodanes 5 (clerodine 5) and ecdysteroids 6 (20-hydroxyecdysone 6). However, the diversity of structure of these products, the diversity of their biological activities and their structural complexity did not allow establishment of unambiguous structure-antifeedant activity relationships.

The scientific interest of the immunological properties of sphingolipids 11-6 and related glycosphingolipids 2 7 has recently increased on account of the role that they could play as therapeutic agents. Their antifongic properties have been the first studied 8. For number of them, immunomodulating activity as well as in vivo antitumoral activities have been reported 9-12. Some other compounds with original chemical structure have also been recently isolated from sponges 13-14

Clerodanes diterpenes have been considerably studied by biologists and chemists, according to their interesting antifeedant activity on insects as well as their unique structure, which make them a challenging target for total synthesis. Several problems related to their synthesis have been solved1,2,3, and some natural products have been synthesised in the ajugarin's series4 as well as in the dehydroclerodanes 4c. However, the problem of the stereoselective construction of the acyclic C-9-C-115 double bond, drastically related to this of the stereochemical control of stereogenic centers C-8, C-10 and C-5 remains up to date. We have developped two stategies aimed to this goal. Both strategies consist in controlling the configurations of some of the stereogenic centers of the target molecule in an early bicyclic structure easy accessible. One of the ring of these precursors should prefigurate the B ring of the clerodanes, the cleavage of the other ring giving access to functionnalized side chains which should allow the further elaboration of either the decalinic moeity of the molecule or the furofuran system through well known methodologies.

Allylic esters of TFA-protected amino acids undergo asymmetric Claisen rearrangements in the presence of cinchona alkaloids, giving rise to g,d-unsaturated amino acids in a highly stereoselective fashion. The products are useful precursors for the short and efficient synthesis of more complex compounds such as substituted 4-hydroxyprolines, 4-hydroxyornithines and iminosugars.