Repetitive synthesis

Keywords Dendrimers, linear aliphatic molecules, oligophenylenes, repetitive synthesis, supramolecular chemistry. 

Because of their high molecular weight and their defined structure, dendrimers offer themselves for studying the expression of chirality on a macromolecular level. The construction of configurationally uniform macromolecules is otherwise a complex task but can be achieved more easily with dendrimers because of repetitive synthesis from identical (chiral) building blocks. Comparison of optical rotation values and circular dichroism (CD) spectra should demonstrate what influence there is of the chiral building blocks on the structure of the whole dendrimer. 

Scheme 6.3 Moore and coworkers repetitive synthesis of linear phenylacetylene sequences capable of undergoing high-yield macrocyclizations.

The term iterative hbrary deconvolution describes a process consisting of repetitive synthesis, screening, and selection steps, during which all mixture positions of the hbrary (see also Section 4.3.7.3.2.1) are successively defined, resulting in the identification of individual peptides with the desired bioactivify.P At each step of this iterative process, the number of peptides per mixture is reduced by a factor equal to the number of amino adds in the mixture position that was defined at that step. At the final step of the process, individual peptides are synthesized and tested. For a hexapeptide library with two defined and four mixture positions, the iterative deconvolution consists of four cycles of synthesis, screening, and selection (see Table 2).P 1... 

In 1978, we reported the repetitive synthesis of noncyclic and cyclic (so called nonskid chainlike ) polyaza compounds, which were the first examples of cascade molecules (Scheme 1). Since that time, dendrimers have gained widespread attention in organic, as well as in inorganic2,3 and physical chemistry.4 In 1992, De Gennes received the Nobel prize in physics for his studies on chaos and fractals. His results are relevant for the molecular design of cascade polymers especially in their three-dimensional growth. 

One common example of repetitive synthetic strategy comes from the field of natural products. The preparation of oligo- and polypeptides is a repeating sequence of protection and activation of the reactants, followed by the addition of a new amino acid. In 1963, one of the highlights in repetitive synthesis was the automation of peptide production by Merrifield8 (Figure 1). In the literature, authors often speak of a protein machine since it is now possible to build up peptides mechanically without the preparative help of a chemist. 

Mekelburger HB, Rissanen K, Voegtle F. 1993. Repetitive synthesis of bulky dendrimers a reversibly photoactive dendrimer with six azobenzene side chains. Chem Ber 126(5) 1161 1169. 

The next UDP-sugar (in this specific case, UDP-GlcUA) was added to the reaction mixture and then applied to the next reactor (converting pentasaccharide into the hexasaccharide with immobilized GlcUA-Tase) to perform the reaction of Equation 3. This repetitive synthesis was continued by adding the next appropriate UDP-sugar and switching enzyme reactors. 

Apart from the major variation in temperature and humidity caused by the seasons, there are more frequent periodic fluctuations that may have played an important role on the repetitive synthesis of biopolymers and facilitated the elongation and replication of polynucleotides. These are, for instance, evaporation, drying and refilling of mainland and coastal pools and lagoons, the similar daily effects of tides, and the fluctuations in temperature between night and day. 

Apart from basis polymers, such as poly(vinyl alcohol), which contain already the functional group for attaching the first nucleoside, the polymer has to be derivatized in many cases in order to obtain the suitably functionalized support [31, 126, 134, 13S]. For the selection of the appropriate functional group, one has to consider that the bond between the port and the oligonucleotide must be resistant to cleavage during the repetitive synthesis. In addition, the same bond should be cleavable at the end of synthesis without... 

To initiate the first step of the repetitive synthesis, the trityl chloride derivative of polystyrene was subjected to reaction with thymidine in pyridine (Scheme 6). It is note-worthy that unreacted trityl chloride groups were blocked as methyl ethers by addition of methanol [41], The thymidine content was found to be 60-340 jumol g" after polymer-analogous cleavage from the support. This capacity corresponds to a degree of functionalization of 15-85% and points to steric problems of this attachment to the polymer. 

The high regio- and diastereoselectivity to be gained from aluminum-chelated transition states was demonstrated with a repetitive synthesis of a polypropionate chain [24]. 

Being ba on solid-phase synthesis in principle, the liquid-phase method for the synthesis of biopolymers is characterized by the same limitations due to polymer reactions. These mainly concern the attachment and retease from the polymer which are the most crucial steps in polymer-supported synthesis. However, additional problems are caused by the heterogeneity of the reactions which decreases the yield considerably. The main reason why this concept has found a widespread application is the ease of experimental procedure, using filtration for separation, thus avoiding the laborious and time-consuming procedure of separation of products from reagents during repetitive synthesis [1-7]. 

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