Polymer-bound compounds

The successful assembly of organic compounds on a solid support represents only part of the challenge in SPOS. After completion of synthetic sequence, the compounds must be cleaved from linkers attached to polymer by a chemical or photochemical reaction, for example, treatment of a polymer-bound compound with acids, bases, nucleophiles, redox reagents, and even photons. Acid-labile linker and amine-cleavable Marshall linker are two major classes of hnkers used in combinatorial synthesis. 

To examine the second way of binding the chloro ester 1-Me to a polymer as in 268 (Fig. 12), the TentaGel-S-COOH resin 279 which contains a succinyl linker, was esterified with the 2 -(4-hydroxybutyl)-substituted chloro ester 280 (prepared by debenzylation of compound 2l-Me) (Scheme 81) [11b]. Only the Michael addition of secondary amines onto 281 and the removal of the adducts 283 from the resin has been probed so far, any further transformations of polymer-bound compounds 281 need yet to be developed. 

The two hnkers can be identical but they can also be different, with the restriction that both need to be cleaved under the same conditions. Simultaneous cleavage results in the cleavage of all polymer-bound compounds. If, after cleavage, the desired compound is stiU attached to linker 2 and the spacer, this indicates incomplete cleavage from hnker 2. On the other hand, if the desired compound is obtained free of hnker 2, this is an indication of a complete cleavage. Hence, the constructs are useful in establishing conditions for the complete removal of the compounds. 

IR microscopy analysis allows the spatially resolved and destruction-free characterization and quality control of polymer-bound compound libraries. Furthermore, by superpositioning of different IR maps, compounds immobilized on individual resin beads can be identified. Through improved embedding techniques, even larger areas with many resin beads can be mapped very quickly, thus improving the statistical evaluation by image analysis. 

The formation of the polymer-bound compounds was routinely monitored by FT-IR of the resin beads. The product composition 300 301 was strongly influenced by differences in nucleophilicity and/or steric hindrance. When those differences were minimal, both possible compounds 300 and 301 were generally formed in 1 1 ratio.i i 32... 

The polymer-bound compound is separated from the mixture and then released. 

Evaporate the filtrate to yield a mixture of alcohol 22 and diol 23 as a yellow oil. Alcohol 22 can then be isolated by column chromatography of the yellow oil using a mixture of hexanes and ethyl acetate (1 1) as eluent (see Note 8). Alcohol 22 is isolated as a colorless oil. The expected yield should be 27% from syn-20, assuming 100% conversion in aU the steps carried out with polymer-bound compounds). 

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