A catalytic enantioselective approach for the formation of chiral CO(2)-synthons is presented. The described methodology is based on the reaction of dienes with diethyl ketomalonate using C(2)-symmetric bisoxazolines as the chiral ligands and copper(II) and zinc(II) as the Lewis acids. For cyclic dienes the reaction proceeds in good yield and with up to 93% ee for 1,3-cyclohexadiene, while for cyclopentadiene the reaction also proceeds well at low temperature, but increasing the temperature leads to a retro-Diels-Alder reaction. The reaction has been studied under different conditions and for various dienes, and it has been found that for activated dienes both the hetero-Diels-Alder and Mukaiyama aldol products are isolated. The compound formed by the enantioselective hetero-Diels-Alder reaction of 1,3-cyclohexadiene with ketomalonate has been converted to both the CO(2)-synthon formed in principle from the [2+4] cycloaddition reaction of CO(2) and 1,3-cyclohexadiene, and attractive optically active 1,4-disubstituted cyclohexene diols. The absolute configuration of the hetero-Diels-Alder adduct has been assigned on the basis of the structure of (1S)-camphanic ester of a 1,4-disubstituted cyclohexene diol which gave suitable crystals for X-ray analysis. The reactions have also been analyzed from a theoretical point of view. First, the [2+4] cycloaddition reaction of CO(2) with 1,3-cyclohexadiene has been investigated, and then the relative stability of the two major isomers of bidentate ketomalonate coordinated to a copper(II) or zinc(II) Lewis acid dication was investigated applying density functional theory calculations. Finally, the energetics of the [2+4] hetero-Diels-Alder addition mechanisms typical of the reaction with normal dienes catalyzed by C(2)-symmetric bisoxazoline-zinc(II) complexes using semiempirical calculations are presented.

The lipopeptide tripalmitoyl-S-glycerylcysteine (Pam3Cys) is derived from the N-terminal part of bacterial lipopeptides and is a polyclonal B-lymphocyte and macrophage activator. Derivatives of Pam3Cys constitute highly potent, nontoxic immunoadjuvants, and lipopeptide−antigen conjugates have found important applications as novel fully synthetic low-molecular-weight vaccines. To establish a possible correlation between molecular structure, aggregation properties, and biological activities, we have studied the self-assembly and monolayer properties of a range of Pam3Cys derivatives using transmission electron microscopy (TEM) and a Langmuir-film balance combined with a Brewster angle microscopy (BAM). It was found that the chirality of the glyceryl moiety and the additional serine unit impacted on the mode of aggregation and the monolayer properties. Correlations are discussed between these physicochemical properties and biological activities.

A novel class of glycopeptidolipids is described, which potentially can be used as a novel antigen-delivery system. The compounds have been prepared by a combination of solid-supported and solution-based methods. The use of the orthogonally protected FmocLysDde derivative provided an opportunity to incorporate two different types lipids. It was found that the model compound 1 forms aggregates in aqueous media which can be described as rod or tubelike structures. The aggregates can be stabilized by topotactic photopolymerization. Studies on the structural analogues 2-5 revealed the effect of the carbohydrate, peptide, and lipid moiety on the aggregation properties. It is concluded that none of the structure elements can lay claim to be exclusively important for the formation of highly organized aggregates such as tubes, fibers, or helical ribbons from 1, but the presence of all of these structural elements afforded the most uniformly shaped extended structures.

A facile and highly efficient synthesis of a glycopeptidolipid containing a heptose sugar, a synthetic T-epitope and a synthetic immunoadjuvant is presented which represents an important step towards the development of a fully synthetic vaccine against Neisseria meningitidis.