Advances in Organic Synthesis

Carbohydrate-protein interactions play a major-role in recognition of cells by external macromolecules. Single saccharide ligands, however, bind only weakly to their protein receptors. Sufficient affinity is achieved by appropriate mutual orientation of the saccharide epitopes and their protein receptors, which allows multiple simultaneous interactions. In other words, high affinity binding is achieved through multivalency, where the high number of simultaneous binding events compensates the lack of strength of an individual interaction. Solid-supported methods allowing synthesis of multiantennary glycoconjugates have, hence, been under active development. The present paper is a review of the solid-phase protocols useful for preparation of glycoconjugates.

This review highlights the development of new receptors based on enantiopure trans-cyclohexane-1,2-diamine, a chiral building block presenting unique structural and conformational properties. Different architectures sharing this structural motif, which were prepared following several synthetic approaches, have been summarized from the recent literature.

Three-membered heterocyclic rings offer a powerful combination of reactivity, stability, availability, and atom economy. In fact, the asymmetric ring opening of allylic epoxides with nucleophiles of different kinds, as will be discussed in this Review, offers the possibility of generating valuable chiral non-racemic building blocks in a very simple manner and in a stereodefined fashion.

Fully conjugated dendrimers are interesting materials as active chromophores for a range of optoelectronic applications. The rigid and well-defined framework of these materials enables structure-property relationships to be more easily understood. In this paper, we summarize the main strategies for the synthesis of poly(phenylenevinylene)- and poly(phenyleneethynylene)-based dendrimers as well as approaches to hybrid dendritic structures that combine both scaffolds. Along with the synthetic features, some physical and chemical properties are also discussed.

Under catalysis with an appropriate Lewis acid, the intermolecular Diels-Alder cycloaddition and intramolecular polyene cyclization of the α-activated cross conjugated cycloalkenone systems, possessing particularly increased dienophilicity/electrophilicity in the cross conjugated double bond, proceeded constantly with a high degree of stereochemical control, leading to a variety of synthetically useful molecules, which may serve as advanced intermediates towards many structurally challenging natural products, especially cis-clerodane diterpenoids. Mechanistically, an additional conjugated double bond incorporated into the cycloalkenone core of the titled systems might contribute synergistically to the classical secondary orbital effects, thus significantly enhancing the endo-to-ketone addition. In addition, a tandem multiple σ-bond migration process, an enzymatic pathway prevalent in nature, was proposed to rationalize the formation of structurally unusual polyene-cyclization products occurring under standard chemical conditions. On the other hand, these highly polarized cross-conjugated compounds was found to be a superior Michael acceptor for Grignard reagents. In that regard, the introduction of ω-unsaturation to the titled substrates via 1,4-addition could serve as a springboard for a diverse array of annulation processes.

This chapter reviews the recent findings on the synthetic methods developed for the direct introduction of a trifluoromethyl group in carbonyl compounds. It was organized by type of reagent highly considering the description of the trifluoromethylating agents, their activation mode, their asymmetric approaches, as well as applications in organic synthesis.

The ubiquity of the piperazine-2,5-dione core (2,5-diketopiperazine, DKP) in natural products and the preponderance of this heterocyclic framework in many bioactive compounds have encouraged the development of methods for the selective functionalization of readily available piperazine-2,5-dione substrates. C-functionalization using DKPs as electrophilic glycine templates is generally mediated by N-acyliminium ions. These intermediates show highly versatile reactivities, which are reflected in an impressive number of synthetic applications. However, even in some highly comprehensive treatments of Nacyliminium ions, references to the construction of these species on piperazine-2,5-dione frameworks are scarce. The present review aims at filling this gap, placing emphasis upon the construction of endocyclic and exocyclic acyliminium ions derived from piperazine-2,5- diones and their synthetic applications. More complex structures that include this framework as a structural fragment, such as pyrazino[1,2-b]isoquinoline-1,4-diones or pyrazino[2,1- b]quinazoline-3,6-diones, are also overviewed.

Incorporation of metal chelating amino acids in protein or peptide sequences helps protein purification due to the metal ion affinity of the protein or peptide. Structure and function of synthetic amino acids with side chain metal complexes have particular importance for extending our understanding of organometallic compounds under physiological conditions and mimic protein folding and stabilization. Chemists are now designing biomimetic organo-metallic amino acids that can form both secondary and tertiary structures through various noncovalent interactions. An overview of the design and synthesis of non-proteinogenic amino acids containing metal ions in the side chain is discussed.