Chemicals inducing seed germination and early seedling development.

Seed germination and early seedling development are essential events in the plant life cycle that are controlled largely by the interplay and cross-talk between several plant hormones. Recently, major progress has been achieved in the elucidation at the molecular level of the signalling of these phytohormones. In this review, we summarise the data for the most promising classes of compounds, which could find potential agronomic applications for promoting seed germination and early seedling development even under abiotic stress conditions. Structural modifications of plant hormones are required to improve their biological performance and their specificity to allow commercial application.

New ventures in the chemistry of avermectins.

An overview is given on recent work towards new avermectin derivatives of extremely high insecticidal and acaricidal activity. These compounds were prepared from commercially available abamectin (avermectin B1) 1. For the synthesis, many novel entries have been opened up, making use of modern synthetic methods and applying them, for the first time, to the chemistry of avermectins. Several types of avermectin derivatives can be regarded as key innovations in the field. These are, in particular, 4''-deoxy-4''-(S)-amino avermectins 3, 4'-O-alkoxyalkyl avermectin monosaccharides 5, 4''-deoxy-4''-C-substituted 4''-amino avermectins 6 and 2''-substituted avermectins 7. 4''-Deoxy-4''-(S)-amino avermectins 3 were obtained by the consecutive application of the Staudinger and Aza-Wittig reaction. 4'-O-Alkoxyalkyl avermectin monosaccharides 5 were prepared by alkoxyalkylation of 5-O-protected avermectin monosaccharide. For the synthesis of 4''-deoxy-4''-C-substituted 4''-amino avermectins 6, several methods were used to construct the fully substituted 4''-carbon centre, such as a modified Strecker synthesis, the addition of organometallics to a 4''-sulfinimine and a modified Ugi approach. In order to prepare 2''-substituted avermectins 7, 5-O-protected avermectin monosaccharide was coupled with carbohydrate building blocks. An alternative synthesis involved the hitherto unknown enol ether chemistry of 4''-oxo-avermectin and the conjugate addition of a cuprate to an avermectin 2'',3''-en-4''-one. In addition, a number of other highly potent derivatives were synthesised. Examples are 4''-O-amino avermectins 8, as well as products arising from intramolecular rhodium catalysed amidations and carbene insertions. A radical cyclisation led to an intriguing rearrangement of the avermectin skeleton. Many of the new avermectins surpassed the activity of abamectin 1 against insects and mites.

Copper-free synthesis of skipped diynes via cross-coupling reactions of alkynylalanes with propargylic electrophiles.

Alkynylalanes provide a new, copper-free route to skipped diynes when combined with propargylic electrophiles bearing an aluminum-complexing leaving group. The reaction is mild, efficient, and, in contrast to copper-mediated methods, highly regioselective. [reaction: see text]

Search for alpha-glucosidase inhibitors: new N-substituted valienamine and conduramine F-1 derivatives.

A solid-phase synthesis of new N-substituted valienamines has been developed and new synthesis of (+/-)-conduramine F-1, (-)-conduramine F-1, and (+)-ent-conduramine F-1 is presented, together with the preparation of N-benzylated conduramines F-1. N-Benzylation of both valienamine and (+)-ent-conduramine F-1 improves their inhibitory activity toward alpha-glucosidases significantly. The additional hydroxymethyl group makes valienamine derivatives more active than their (+)-ent-conduramine F-1 analogues.

New method based on 1-(trimethysilyl)alk-1-yne to prepare 1,4-skipped diynes.

[reaction: see text] We have developed a novel reaction between a terminal TMS-alkyne and a propargyl halide in the presence of a fluoride source and a catalytic amount of copper iodide to prepare 1,4-skipped diynes with good yields and in mild conditions. We have shown that this reaction also works very well with germanium and tin derivatives as an alternative to silicon. This new method can be useful for the synthesis of polyunsaturated fatty acids.

Recognition of RNA by amide modified backbone nucleic acids: molecular dynamics simulations of DNA-RNA hybrids in aqueous solution.

Thermodynamic and structural properties of a chemically modified DNA-RNA hybrid in which a phosphodiester linkage is replaced by a neutral amide-3 linkage (3'-CH(2)-CONH-5') were investigated using UV melting experiments, molecular dynamics simulations in explicit water, and continuum solvent models. van't Hoff analysis of the experimental UV melting curves suggests that the significant increase of the thermodynamic stability of a 15-mer DNA-RNA with seven alternated amide-3 modifications (+11 degrees C) is mainly due to an increased binding enthalpy. To further evaluate the origin in the observed affinities differences, the electrostatic contribution to the binding free energy was calculated by solving the Poisson-Boltzmann equation numerically. The nonelectrostatic contribution was estimated as the product of a hydrophobic surface tension coefficient and the surface area that is buried upon double strand formation. Structures were taken from 10 ns molecular dynamics simulations computed in a consistent fashion using explicit solvent, counterions, and the particle-mesh Ewald procedure. The present preliminary thermodynamic study suggests that the favorable binding free energy of the amide-3 DNA single strand to the complementary RNA is equally driven by electrostatic and nonpolar contributions to the binding compared to their natural analogues. In addition, molecular dynamics simulations in explicit water were performed on an amide-3 DNA single strand and the corresponding natural DNA. Results from the conformations cluster analysis of the simulated amide-3 DNA single strand ensembles suggest that the 25% of the population sampled within 10 ns has a pre-organized conformation where the sugar C3' endo pucker is favored at the 3'-flanking nucleotides. These structural and thermodynamic features contribute to the understanding of the observed increased affinities of the amide-3 DNA-RNA hybrids at the microscopic level.

Diastereofacial Selective Addition of Ethynylcerium Reagent and Barton-McCombie Reaction as the Key Steps for the Synthesis of C-3'-Ethynylribonucleosides and of C-3'-Ethynyl-2'-deoxyribonucleosides.

We describe the preparation of 3'-alkynyluridine 4a and -adenosine 4b and of 3'-alkynyl-2'-deoxyuridine 16a and -adenosine 16b starting from the corresponding nucleosides. The desired stereochemistry of the C-3' tertiary alcohol was obtained by reaction of an ethynylcerium-lithium reagent on a 3'-ketonucleoside with the hydroxyl group at C-5' unprotected. The 2'-deoxygenation was performed by a Barton-McCombie reaction under appropriate conditions where the addition of tin hydride to the triple bond was suppressed. Evaluation of the anti-HIV activity of the C-3' modified nucleosides is reported.