Highly cross-linked polymeric supports

Details Highly cross-linked polymeric supports Highly cross-linked polymeric supports

1997-06-06

1999-06-08

Schofer, Joseph L.

Synthetic resins or natural rubbers -- part of the class 520 ser

Synthetic resins

Polymers from only ethylenic monomers or processes of...

C08F 1800

Patent

active

059105542

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

An increasing array of organic chemical reactions, e.g., acylations, alkylations, enolate additions, Wittig reactions, reductions, oxidations, etc., that are traditionally carried out in homogeneous solution are now being adapted for solid-phase synthesis. For this reason, there is a large demand for suitable polymeric supports. For the most well-studied case, i.e., solid-phase peptide synthesis (SPPS), a wide range of materials have been developed.
Mertifield's original studies, and much subsequent work, used low (1963)!. Polystyrene, however, is limited in the number and variety of solvents that can be used. Because peptide synthesis takes place within a one aspect that has been considered in the development of supports for SPPS is how well the material swells. To ensure good swelling properties, most polymeric supports used previously for this purpose have had a minimum amount of crosslinking consistent with mechanical stability. Generally, it is believed that the more crosslinking, the more mechanically stable is the polymer, but the less swellable it is. Thus, polymers used as solid supports have been developed to balance swelling with mechanical stability by using a low level of crosslinker (e.g., typically less than about 10 mole- % and usually only about 1-2 mole- %).
For SPPS, another consideration is to produce a support of the same polarity as the peptide backbone. Sheppard and coworkers developed a Soc., Perkin Trans. I, 529-537 (1981)!. This material, however, has not been commercially successful. Another consideration, of particular importance for continuous-flow procedures, is the mechanical stability of the support. Efforts to develop materials for this purpose resulted in Commun., 1589-1591 (1989)!.
Earlier work in the area of solid-phase synthesis also focused on supports that comprise polyethylene glycol (PEG) grafted onto low crosslinked polystyrene (PS). The resultant PEG-PS can be used in continuous-flow processes, has good swelling properties, and shows good compatibility with No. 5,235,028 (Barany et al.)!. Solid-phase peptide synthesis procedures and supports are summarized, for example, by G. Barany et al., Int. J. Peptide Protein Res. 30 705-739 (1987) and J. M. Stewart et al., Innovation and Perspectives in Solid Phase Synthesis: Peptides, Polypeptides, and Olizonucleotides. Macro-organic Reagents and Catalysts, R. Epton, Ed., SPCC UK Ltd., 1-9 (1990).
A need exists for other polymeric supports, particularly for solid- phase synthesis, but also for applications in chromatography, immobilization, etc.


SUMMARY OF THE INVENTION

The polymers of the present invention are prepared from multifunctional oxyacetylene- or oxypropylene-containing (meth)acrylate crosslinkers and optional secondary crosslinkers and olefin-containing monomers, preferably functionalized olefin-containing monomers. The multifunctional (meth)acrylate crosslinkers used in making the highly crosslinked polymers of the present invention are represented by the following formula (I): ##STR2## wherein R.sup.1, R.sup.2, and R.sup.3 are each independently hydrogen (acrylate) or a methyl group (methacrylate); R.sup.4 is hydrogen or an organic group or substituent that can interact in the polymerization and/or crosslinking process or is nonreactive under the conditions of the polymerization and/or crosslinking process; R.sup.7, R.sup.8, and R.sup.9 are each independently --CH.sub.2 --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --CH.sub.2 --, --CH(CH.sub.3)--CH.sub.2 --, or --CH.sub.2 --CH(CH.sub.3)--(preferably --CH.sub.2 --CH.sub.2 --); and each of 1, m, and n is no greater than about 100 with the proviso that at least one of 1, m, or n is at least 1 (preferably each of 1, m, and n is 1-30, and more preferably 1+m+n total 5-25). The crosslinkers are polymerized with one or more olefinic monomers optionally functionalized with amino groups, carboxyl groups, hydroxyl groups, etc. The synthesis of the polymers of the present invention is particularly advantageous because it occurs in one step.


BRIEF

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