Template host-guest

Vogtle has developed this approach further and employed a series of anionic templates to prepare rotaxanes (instead of the neutral template in the above reaction) [65-67]. In this approach a phenolate, thiophenolate or sulfonamide anion is non-covalently bound to the tetralactam macrocycle (46) forming a host-guest complex via hydrogen bonding (see Scheme 21). 

Loeb has reported a series of pseudorotaxanes [84,85] and rotaxanes [86,87] where C-H- 0 hydrogen bonding interactions (together with N+- -O attractive forces) play an important contribution in templating the formation of the interlocked species. In particular, the formation of a pseudorotaxane was observed when equimolar amounts of [pyCH2CH2py]2+ and the crown ether 20 were mixed. The structural characterization of the resulting host-guest complex... 

Chemical templates are being increasingly employed for the development of dynamic combinatorial libraries (DCL) [94-98]. These (virtual) libraries of compounds are produced from all the possible combinations of a set of basic components that can reversibly react with each other with the consequent potential to generate a large pool of compounds. Because of the dynamic equilibria established in a DCL, the stabilization of any given compound by molecular recognition will amplify its formation. Hence the addition of a template to the library usually leads to the isolation of the compound that forms the thermodynamically more stable host-guest complex (see Scheme 37). 

From the viewpoint of stereochemistry, Sections 5.2-5.4 focus on the templated/amplified components of the DCL itself, with the emphasis on how diastereomeric receptors differentially respond to the host-guest assay. Spectacular structures have emerged from the internal competition for the best binder(s) to an analyte. 

In order to show that HIT-1 was a-helix compatible and induces a-helical conformations in short peptides from the N- and C-terminus as well as from internal positions, template-linked peptides have been compared to nonconstrained reference peptides. In the N- and C-cap projects a hydrophobic 12-mer peptide was used as a standard reference. The 12-mer reference peptide 104 was originally developed for host guest experiments to evaluate the a-helix propensities of unnatural amino acids (see Section II.A) and had later been used to confirm N-cap induced helix formation.141,202,214 In the C-cap series and for position-independent templates the same reference peptide could be used after minor modification of the terminal protection groups. The suitably protected reference peptide and the corresponding template-linked model peptides used for the evaluation of N-terminal, C-terminal, and internal helix induction are depicted in Figure 39. 

From your reading of Section 6.7, guess possible values for the template ratios for the synthesis of 6.98 in NMP in the presence of the following guests. Consider the influence of molecular size and shape, as well as host-guest interactions such as C— FI hydrogen bonds, n-nstacking etc. 

Fortunately, more efficient methods for the complexation of macrocyclic hosts with acyclic guest molecules have become available with the advent of supramo-lecular chemistry, resulting in higher yields in rotaxane and catenane synthesis. In the following sections, the preparation of different types of interlocked molecules, with the use of host-guest recognition, is discussed. It should be noted that these template-directed methods differ significantly from the above-mentioned stochastic approach [28]. 

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