Antitumor agents possibly better than taxol might be drived from the epothilones (depicted on the right), which likewise bind to microtubules. The epothilones, which were discovered by Höfle et al. and Reichenbach et al., are easier to synthesize and more soluble in polar solvents than taxol. The results of in vivo activity studies are now eagerly awaited. The exceptional importance of these new tubulin stabilizers is reflected in the race for synthetic approaches to these compounds that has already led to the first total syntheses and several partial solutions.

Möglicherweise noch bessere Cytostatica als Taxol sind die von den Arbeitsgruppen Höfle und Reichenbach entdeckten Epothilone (siehe rechts), die ebenfalls an Tubulinaggregate binden. Obendrein sind sie relativ leicht zu synthetisieren und in polaren Lösungsmitteln gut löslich. Mit Spannung werden nun die Ergebnisse aus In‐vitro‐Aktivitätsstudien erwartet. Die außergewöhnliche Bedeutung dieser neuen Tubulinstabilisatoren spiegelt sich in einem Wettlauf um synthetische Zugänge wider, der zu den ersten Totalsynthesen und zahlreichen Teillösungen führte.

0

The tissue-specific and development-dependent accumulation of secondary products in roots and mycorrhizas of larch (Larix decidua Mill.; Pinaceae) was studied using high-performance liquid chromatography and histochemical methods. The compounds identified were soluble catechin, epicatechin, quercetin 3-O-[alpha]-rhamnoside, cyanidin- and peonidin 3-O-[beta]-glucoside, 4-O-[beta]-hydroxybenzoyl-O-[beta]-glucose, 4-hydroxybenzoate 4-O-[beta]-glucoside, maltol 3-O-[beta]-glucoside, and the wall-bound 4-hydroxybenzaldehyde, vanillin, and ferulate. In addition, we partially identified a tetrahydroxystilbene monoglycoside, a quercetin glycoside, and eight oligomeric proanthocyanidins. Comparison between the compounds accumulating in the apical tissue of fine roots, long roots, and in vitro grown mycorrhizas (L. decidua-Suillus tridentinus) showed elevated levels of the major compounds catechin and epicatechin as well as the minor compound 4-hydroxybenzoate 4-O-[beta]-glucoside specifically in the root apex of young mycorrhizas. The amounts of wall-bound 4-hydroxybenzaldehyde and vanillin were increased in all of the mycorrhizal sections examined. During the early stages of mycorrhization the concentrations of these compounds increased rapidly, perhaps induced by the mycorrhizal fungus. In addition, studies of L. decidua-Boletinus cavipes mycorrhizas from a natural stand showed that the central part of the subapical cortex tissue and the endodermis both accumulate massive concentrations of catechin, epicatechin, and wall-bound ferulate compared with the outer part of the cortex, where the Hartig net is being formed.

Jasmonic acid is distributed throughout higher plants, synthesized from linolenic acid via the octadecanoic pathway. An important and probably essential role seems to be its operation as a ‘master switch’, responsible for the activation of signal transduction pathways in response to predation and pathogen attack. Proteins encoded by jasmonate-induced genes include enzymes of alkaloid and phytoalexin synthesis, storage proteins, cell wall constituents and stress protectants. The wound-induced formation of proteinase inhibitors is a well-studied example, in which jasmonic acid combines with abscisic acid and ethylene to protect the plant from predation.

Methyl 3-methyljasmonate was synthesised from methyl jasmonate via methyl 3,7-dehydrojasmonate. Molecular modelling predicted an increase in the proportion of cis-orientated side-chains for equilibrated 3-methyl-substituted jasmonate. The synthetic 3-methyljasmonate was shown by gc-ms analysis to equilibrate to a 2:1 ratio of isomers, which appeared from the NMR spectra to comprise mainly the cis-isomer. Surprisingly, both 3,7-dehydro- and 3-methyl-derivatives were inactive in four well established jasmonate bioassays. Methyl-2-methyljasmonate was synthesised and also found to be inactive. Methyl 4,5-dehydrojasmonate was prepared, via the 5-diazo derivative. Both of these compounds have low activity. Our results are discussed with reference to previous knowledge of jasmonate structure-activity relationships and indicate that there are stringent steric demands in jasmonate-receptor interactions.

The synthesis of 24-epicathasterone (20), 22-deoxy-24-epiteasterone (22) and 24-hydroxy-6-oxo-24-epicampestanol (24) via 22,23-epoxy- and 22,23-bromohydrin intermediates starting with ergosterol is reported. The structures of the new brassinosteroids were determined especially by X-ray analysis of intennediate bromohydrins.The synthesis of 24-epicathasterone, 22-deoxy-24-epiteasterone and 24-hydroxy-6-oxo-24-epicampestanol via 22,23-epoxy- and 22,23-bromohydrin intermediates starting with ergosterol is reported. The structures of the new brassinosteroids were determined especially by X-ray analysis of intermediate bromohydrins.

Uridine 5′-diphosphoglucose:betanidin 5-O- and 6-O-glucosyltransferases (5-GT and 6-GT; EC 2.4.1) catalyze the regiospecific formation of betanin (betanidin 5-O-β-glucoside) and gomphrenin I (betanidin 6-O-β-glucoside), respectively. Both enzymes were purified to near homogeneity from cell-suspension cultures of Dorotheanthus bellidiformis, the 5-GT by classical chromatographic techniques and the 6-GT by affinity dye-ligand chromatography using UDP-glucose as eluent. Data obtained with highly purified enzymes indicate that 5-GT and 6-GT catalyze the indiscriminate transfer of glucose from UDP-glucose to hydroxyl groups of betanidin, flavonols, anthocyanidins and flavones, but discriminate between individual hydroxyl groups of the respective acceptor compounds. The 5-GT catalyzes the transfer of glucose to the C-4′ hydroxyl group of quercetin as its best substrate, and the 6-GT to the C-3 hydroxyl group of cyanidin as its best substrate. Both enzymes also catalyze the formation of the respective 7-O-glucosides, but to a minor extent. Although the enzymes were not isolated to homogeneity, chromatographic, electrophoretic and kinetic properties proved that the respective enzyme activities were based on the presence of single enzymes, i.e. 5-GT and 6-GT. The N terminus of the 6-GT revealed high sequence identity to a proposed UDP-glucose:flavonol 3-O-glucosyltransferase (UF3GT) of Manihot esculenta. In addition to the 5-GT and 6-GT, we isolated a UF3GT from D. bellidiformis cell cultures that preferentially accepted myricetin and quercetin, but was inactive with betanidin. The same result was obtained with a UF3GT from Antirrhinum majus and a flavonol 4′-O-glucosyltransferase from Allium cepa. Based on these results, the main question to be addressed reads: Are the characteristics of the 5-GT and 6-GT indicative of their phylogenetic relationship with flavonoid glucosyltransferases?

Quantitative 2D NOE measurements and restrained molecular dynamics simulations (with explicit solvent) were carried out in order to determine preferential solution side chain conformations of the two most important native brassinosteroids, brassinolide and 24‐epibrassinolide. The NOE assignment was assisted by 1D NOE difference spectroscopy and included prochiral assignment of the side chain methyl groups Me‐26 and Me‐27. 2D NOE intensities were converted into inter‐proton distances using the ‘complete relaxation matrix analysis’ methodology. Restrained molecular dynamics simulations in a chloroform solvent box led to a well defined solution conformation in the case of brassinolide. The increased side chain flexibility in the case of 24‐epibrassinolide is discussed, considering missing NOE correlations and vicinal proton coupling constants.

In addition to khasianine, solamargine, xylosylsolamargine and solasonine, three steroidal alkaloid glycosides, solasuaveoline, dihydrosolasuaveoline and isosolasuaveoline, have been isolated from aerial parts of Solanum suaveolens. The structures have been assigned by NMR investigations as (25R)-3β-{O-β-d-glucopyranosyl-(1 → 2)-O-β-d-glucopyranosyl-(1 → 4)-[O-α-l-rhamnopyranosyl-(1 → 2)]-β-d-galactopyranosyloxy}-22αN-spirosol-5-ene, (25R)-3β-{O-β-d-glucopyranosyl-(1 → 2)-O-β-d-glucopyranosyl-(1 → 4)-[O-α-l-rhamnopyranosyl-(1 → 2)]-β-d-galactopyranosyloxy}-5α,22αN-spirosolane and (25R)-3β-{O-β-d-glucopyranosyl-(1 → 6)-O-β-d-glucopyranosyl-(1 → 3)-[O-α-l-rhamnopyranosyl-(1 → 2)]-β-d-galactopyranosyloxy}-22αN-spirosol-5-ene, respectively.