Iterative block synthesis

For this synthesis a photolabile link-up to a Merrifield-type resin was used. The following summarizes the synthesis, which elegandy combines the advantages of solid-phase synthesis with that of iterative block synthesis ... 

Iteration and sequential glycosidation in a stepwise manner or by block synthesis (e.g., disaccharide donor and disaccharide acceptor for tetrasaccharide synthesis)... 

The repeated succession of similar reaction sequences for the stepwise synthesis of molecules which consist of repeated building blocks has been termed in literature as repetitive or iterative synthesis. To a molecule with a defined framework having one or more functional groups A (Fig. 1) an identical molecule unit is attached (Iter. 1). Subsequently the functional groups are then reobtained (Iter. 2) so that the reaction sequences can be repeated over and over with the molecule growing by one unit in each reaction cycle (Iter. 1 + 2). This growth... 

Meijer and co-workers also used a divergent dendrimer synthesis to prepare AB diblock structures (Figure 7.13B) in which the polystyrene linear block is used to initiate growth of the polypropylene imine) dendritic block [45], An amino end group had to be introduced in the polystyrene as a core for subsequent growth of the dendritic fragment via an iterative protocol of sequential... 

Its design versatility, as generic dendrons may be prepared to be used later as building blocks in conjunction with other reactive molecules, or coupled to a multifunctional core to afford functional dendrimers, dendritic-linear hybrids, dendronized polymers, etc. This may be a particularly significant advantage if the coupled reactive or core molecule is itself sensitive to the reaction conditions used in the multiple steps of the iterative synthesis of a dendrimer. 

Similarly, iterative NRPSs operate in a linear fashion but utilize at least one domain or module multiple times for the synthesis of a single NRP product. Thus, peptides assembled by iterative synthetases contain short, repeating units of peptide building blocks. In such systems, the terminal PCP-TE (or infrequendy PCP-C) didomain is responsible for both condensation of the repeating peptide units and chain release from the assembly line. NRPs biosynthesized in this manner include enniatin, enterobactin, bacillibactin, " gramicidin and the depsi-peptides valinomycin and cereulide. Of these examples, condensation of the precursor peptides for both enterobactin and gramicidin S has been extensively studied and will be discussed in detail. 

Three categories of synthetases are distinguished, based on their substrate specificity and mode of product synthesis. The two known types of polyketide synthetases (PKSs) (Type I and II) utilize acyl-coenzyme A (CoA) monomers while nonribosomal peptide synthetases (NRPSs) use amino acids and their analogs as substrates. Type I PKS and NRPS oligomerize these building blocks by a modular assembly-line arrangement while type II PKS iteratively assembles monomeric units. 

Solid-phase synthesis has also been used to make peptoids, some examples of which are shown in Fig. 2.4. Compounds of general structure 2.8, where the amino acid side chain is on the nitrogen, have been prepared either by the corresponding Fmoc-protected N-aUcylated glycines (33) or, in an improved method, via treatment of a resin-bound secondary amine with bromoacetic acid to produce the first peptoid building block, which is then elaborated via iteration of the procedure (34). Other modified P-peptoid structures such as 2.9 with repeating P-amino propionic units have been prepared by acylation of a resin-bound amine with acriloyl chloride followed by Michael addition of a primary amine. The cycle is repeated to build up the polymer... 

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