Biogenetically orientated enantioselective syntheses of the bicyclic-ether substructure of Azadirachtin and of the spirocyclohexenone building block for the Agelorines are communicated. In the first case the kinetic resolution of a cyclopentenone starting material is exercised in a high pressure Diels-Alder cycloaddition and in the second case the cycloadduct of a prochiral spirocyclohexadienone is used for the differentiation of enantiotopic groups.

N-Glycosyl imines show an efficient diastereofacial differentiation in their reactions with nucleophiles. Coordination to suitable Lewis acids enhances this effect, which is demonstrated in the enantioselective syntheses of -amino acids, homoallylamines and -amino acids. Asymmetric aza Diels-Alder and tandem Mannich-Michael reactions have been applied for the enantioselective synthesis of chiral piperidine derivatives including alkaloids, e.g. anabasin, gephyrotoxin 167B, pumiliotoxin C and its 4a-epimer.

Asymmetric syntheses of furyl alcohols and amines, as well as kinetic resolution of racemic mixtures of furylcarbinols are described. Some examples of asymmetric alkyl-
ation of furan derivatives and preparation of butenolides are also presented.

The asymmetric [2+2]cycloadditions of chlorosulfonyl isocyanate to vinyl ethers derived from sugars and hydroxy acids are presented. The account focuses on various aspects of the cycloaddition and on the transformations of the resulting [2+2]cycloadducts into clavams and 1-oxacephams. In order to rationalize the results of direction and magnitude of [2+2]cycloaddition, the stereochemical models of this reaction are discussed.

From epoxy sugars, neighbouring an O-triflyl residue, efficient short-cut new routes to aminodeoxy, (amino acid)-deoxy, cyclopropanated, -hydroxyketo or -butyrolactone pyranoses are developed.

Efficient and economic syntheses of multifunctional dihydrofurans, tetrahydrofurans and -lactones are described. The regiochemistry of the ring junctions of the annulated oxa ring systems are controlled using temporary or permanent protection of the C-4 hydroxyl group.

The fragment C1-C9 of tylonolide was synthesized by stereoselective functionalization of the acyclic enedione 71, obtained via transformation of a 2-methylfuran derivative 68.

The evaluation of RNAse active site model systems based on rigid steroid templates is described. Our preliminary work on steroid derived RNAse model systems showed that preorientation of guanidinium groups and one imidazole moiety leads to active compounds. We found that within the corticosterone derived steroid series, the C11--configurated compounds were superior to their -diastereomers. In order to evaluate the influence of the conformational flexibility of the imidazole group, a flexible side chain was introduced at C17. The fact that this more flexible imidazole group leads to a decrease in the hydrolytic behavior of the steroid derivative further validates our approach of establishing a preorientated RNAse model system for an efficient RNA hydrolysis.

A mild three-dimensional orthogonal protection scheme, based on Nps/Fmoc-groups for -amino, benzyl residues for hydroxyl and carboxyl protection and 2-chlorotrityl esters as anchoring linkage proved to be a new effective approach for the synthesis of glycopeptides. The oligosaccharide moiety of the nephritogenoside glycopeptide is conveniently assembled via phenyl thioglycosides as glycosyl acceptors and phenyl thioglycosyl sulfoxides as donors, readily accessible from the thioglycosides by oxidation with m-chloroperbenzoic acid.

Possible routes leading from Amadori product precursors to glucose-derived protein crosslinks has been suggested by model studies examining the fate of the Amadori products in vitro. For instance, the Amadori product can undergo dehydration to give 1,4-dideoxy-1-alkylamino-2,3-hexodiulose (AP-dione), which has been isolated by trapping with aminoguanidine. In a model reaction, we selected as an AGE target the dipeptide N-Z-arg-lys. The proximity of the arginine and lysine residues to each other promotes stable intramolecular crosslink formation. Incubation of N-Z-arg-lys with 10 equivalents of glucose in 0.2 M phosphate buffer (pH 7.4) at 37°C for five weeks produces at least 25 distinct reaction products upon fractionation of this mixture by HPLC. Each fraction was isolated, concentrated, and analyzed for its reactivity with a polyclonal anti-AGE antibody (RU) that has been shown previously to recognize a class of AGEs that increase as a consequence of hyperglycemia and which are inhibited from forming in human subjects by treatment with the advanced glycation inhibitor aminoguanidine. The products present within one fraction (1.5% yield) were found to block antibody binding in a dose-dependent fashion. Further purification of this fraction by HPLC revealed the presence of one major (0.6% yield) immunoreactive compound. Characterization of this adduct by UV, ESMS and ¹H-NMR spectra revealed the presence of intramolecular arg-lys-imidazole crosslink. This crosslink is non-fluorescent and acid labile and may represent an important class of immunoreactive AGE-crosslinks that form in vivo.

The carbohydrate moieties, linked to mistletoe lectin I (ML-I) are characterized by enzymatic digestion of the individual A and B chains (MLA and MLB), HPLC separation of the (glyco)peptide digests and their sequence and mass spectrometric analysis. All carbohydrate chains are linked via Asn residues to the MLA protein molecule. A xylomannose-type oligosaccharide (I) structure (Man₃Xyl₁Fuc₁GlcNac₂) is attached to the Asn¹¹² residue of the A chain. Three different glycosylation sites are identified for the B chain: oligosaccharide (I) is bound to position 61, oligosaccharide II (Man₆GlcNac₂) is found to be linked to Asn⁹⁶ as well as Asn¹³⁶ residues. In homologous mistletoe lectins, isolated from different harvest batches, oligosaccharide III (Man₅GlcNac₂) is attached to Asn¹³⁶ instead of oligosaccharide II

The classical valence isomers of benzene, namely Dewar-benzene, benzvalene, and prismane, are well known. Phospha-, azaphospha-, and diphosphabenzenes as well as the Dewar and benzvalene derivatives with the same combinations of heteroatoms are described in this review. Phospha- and azaphosphaprismanes are now also known and discussed. Starting materials for these compounds are the kinetically stabilized cyclobutadienes, azacyclobutadienes, as well as the short-lived 1,3-diphosphacyclobutadienes which, upon reaction with phosphaalkynes, provide an access to the mentioned classes of compounds (Scheme 1).

Selected examples of oxidative nucleophilic aromatic substitution in nitroarenes are discussed with emphasis on the authors results. Generalization of this process is attempted.

For a number of examples strategies are developed and explained how structures of complex natural products, such as triterpene glycosides and related compounds, can be efficiently elucidated by application of modern one- and two-dimensional NMR techniques.

It was shown that nitrogen NMR is a powerful tool in the studies of different types of hydrogen bridges (NHN)⁺, (NHN)^-, (NHN), and (NHO). Some of the NMR parameters, originally proposed by us, provide information about the charge redistribution and the extent of proton transfer. The character of hydrogen bonds depend upon solvent, temperature and the physical phase. The results of studies in the solid state using the ¹⁵N NMR CP MAS method were also discussed.

Several Lewis glycolipds were characterized by homo- and heteronuclear NMR methods. The experimental NOE data served as restraints in molecular dynamics simulations. The common structural motif was mimiced by a tetrasaccharide building block with a central trehalose moiety.

The solvation of sucrose and other carbohydrates in DMSO and water is probed by intermolecular NOE measurements. The NOE effects are interpreted in terms of specific binding of the solvent to certain sites of the molecules. It is shown that DMSO attaches to specific sites of the sucrose molecule, whereas for water such a clear differentiation cannot be proven.

Derivatives of mesoionic 1,2,3,4-thiatriazolo-5-aminides, 1 and 2, interact strongly with metal cations. The interactions with Pb(II), Fe(II), Fe(III), Cu(II) and Cd(II) were studied by means of UV-VIS spectroscopy, ¹H and ¹¹³Cd NMR. The stoichiometry of the complex was determined by Job's method. Few species, being in equilibrium in the solution, are found in most cases. Some cations form insoluble materials with thiatriazoles 1 and 2. Ligand 2 interacts with cadmium acetate giving a 2:1 complex with a stability constant (4.3 ± 0.5) × 10⁷ mol^-2.

Any chirality measurements, e.g. circular dichroism (CD) or helical twisting power (HTP), should offer a possibility to develop a method for the determination of the absolute configuration. Measurements of CD and optical rotatory dispersion (ORD) have been used as standard methods for decades. Since the HTP is very sensitive to variations in the molecular structure, the question of the conditions under which determination of HTP can also be used as a method for the determination of the absolute configuration has been analyzed. It has been found, that a sector rule can be developed for a specific class of compounds. A quadrant or octant rule can be applied successfully for mono- and bis-aminoanthraquinones, as has been shown by a correlation of HTP with the CD of the long-wavelength charge transfer band. However, a rule of this type breaks down for compounds with low HTP and CD values.

Optically active carboxylic acids can act as uni- or bidentate ligands in complexes of general formula [M₂(O₂CR)₄]^+k X^-k (M = Mo, Rh or Ru). An in situ exchange of ligand(s) gives rise to several Cotton effects in the spectral range from 800 to 200 nm. In the case of molybdenum complexes with optically active hydroxy and amino acids a hexadecant rule is valid for the two Cotton effects between 400 and 300 nm. For rhodium and ruthenium complexes it was found that the sign of Cotton effects at around 600 nm can be correlated with the structure of investigated acids.