Resins macrocycle function

The first task was to design a linker between the primary amine functionality on the resin and the hydrazine function that ultimately binds the macrocyclic aldehyde. As mentioned above, the employed resin (PEGA1900) features a primary amino group at the end of a PEG spacer connected to the polyacrylamide backbone. To assure monofunctionalization, the amino group was monobenzylated, thereby preventing possible proximity problems. Subsequently, the resulting secondary amine was provided with a handle for the introduction of the hydrazine functionality (see Scheme 29). 

In addition to post-functionalizing polymers by bonding the macrocycle to the preformed polymer backbone, macrocycles can be incorporated into polymer matrices by direct polymerization of the macrocycle, either by a step-growth mechanism or a chain-growth mechanism. [46] Polymeric crown ether stationary phases were pioneered by Blasius et al. [34, 59-62] These resins were used to separate both cations (including protonated amines) with a common anion, and anions with a common cation in high... 

However, the ability of gold(III) chloride to provide protic catalysis under exceptionally mild conditions is further demonstated by two recent examples the hydroxyallene 35 bearing a silyl protecting group is efficiently cyclyzed to give the 2,5-dihydrofuran 36 without deprotection [20] other acidic catalysts which in principle sufficiently promote this type of cyclization - such as HC1 gas or Amberlyst 15 resin - are of course much less compatible with acid sensitive functionalities. Also for the formation of macrocycle 39 gold(III) chloride turned out to be the catalyst of choice [21],... 

Muscone (40) is a sex pheromone of the musk deer and a chemical component of cosmetics. A 12-member library of racemic muscone analogs was synthesized by Nicolaou et al.," who anployed a cyclorelease method on solid support to form the macrocycle scaffold (Figure 11.17). A phosphonate-functionalized resin loaded on encoded SMART microreactors 36 was coupled to olelinic esters 35 to form the p-ketophosphonates 37. Sorting and cross olefin metathesis of 37 with two alkenols followed by oxidation with Dess-Martin reagent gave aldehydes 38. An intramolecular ketophosphonate-aldehyde condensation (Homer-Emmons-Wadsworth reaction) of 38 caused smooth cyclorelease of macrocyclic enones 39. Parallel solution-phase chemistry completed the sequence. 

As described in Section 11.7.1, palladium (0) chemistry has been found particularly well-suited for constructing macrocyclic structures and, hence, applications for libraries have also been pursued. Indeed, as already noted, one of the first macrocyclic library efforts actually used the Heck reaction for solid phase construction of small collections of 20- to 24-membered semi-peptidic macrocycles (299, Figure 11.26, site of ring closure and chemistry indicated). In addition, modest-sized libraries of RGD mimic macrocycles (300) ° and macrosphelide analogues (301) were prepared using palladium-catalysed cyclocarbonylation on resin. This particular method proved to be tolerant of a variety of functional groups, including halides, ethers, ketones and esters. 

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