Polymer-supported chemistry has undergone a dramatic revival. The primary impetus has been the development of """"""""small-molecule"""""""" combinatorial technology for drug discover. However, despite the popularity and successes of resins such as cross-linked polystyrene, insoluble polymers have a number of drawbacks for use in organic synthesis. There can be detrimental effects on reaction rates, selectivities and yields. and spectroscopic analyses are hampered. Furthermore, solid supports are not particularly effective in water. Hence, a number of currently valuable biocatalytic transformations can not be efficiently performed. A soluble support would allow the expectations and methods of traditional solution chemistry, while affording the benefits of the polymer phase. The investigators have embarked on a multifaceted program to develop the utility of soluble polymers in organic synthesis. This includes the discovery of unique soluble polymers for synthetic applications. Significantly a method coined """"""""parallel polymer synthesis"""""""" will provide access to a large number of novel materials. Finally, examples are presented that highlight the power of soluble technology in the synthesis of complex molecules such as prostanoids and chiral building blocks. This will include library construction and the implementation of a polymer- supported technique termed the """"""""oscillating liquid phase"""""""" made possible by the variance in physical properties of our new co-polymers. It is anticipated that soluble-polymer supports will finding increasing utility in synthesis in the coming years.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM056154-02
Application #
6019302
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1998-09-30
Project End
2002-09-29
Budget Start
1999-09-30
Budget End
2000-09-29
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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Lee, Sang-Hyeup; Clapham, Bruce; Koch, Guido et al. (2003) Solid-phase rhodium carbenoid N-H insertion reactions: the synthesis of a diverse array of indoles. J Comb Chem 5:188-96
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Reed, Neal N; Delgado, Mercedes; Hereford, Kristina et al. (2002) Preparation of soluble and insoluble polymer supported IBX reagents. Bioorg Med Chem Lett 12:2047-9
Spanka, Carsten; Wentworth Jr, Paul; Janda, Kim D (2002) Developing soluble polymers for high-throughput synthetic chemistry. Comb Chem High Throughput Screen 5:233-40
Shimomura, Osamu; Clapham, Bruce; Spanka, Carsten et al. (2002) Application of microgels as polymer supports for organic synthesis: preparation of a small phthalide library, a scavenger, and a borohydride reagent. J Comb Chem 4:436-41
Clapham, B; Spanka, C; Janda, K D (2001) Solid-phase rhodium carbenoid reactions: an N-H insertion route to a diverse series of oxazoles. Org Lett 3:2173-6

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