New developments in chemical library synthesis. Norbornenyl tags for use in phase-switching, sequestration, capture-release and soluble support applications

Current Opinion in Drug Discovery and Development

Volumn 5, Issue 4, 2002, Pages 571-579

  Flynn, Daniel L ^a   Hanson, Paul R ^b   Berk, Scott C ^a   Makara, Gergely M ^a  

^a NeoGenesis Pharmaceuticals Inc   (United States)

^b UNIVERSITY OF KANSAS   (United States)

Author keywords

Chemical tagging; Combinatorial chemistry; In situ polymerization; Phase switching; Resin capture; Ring opening metathesis polymerization

Indexed keywords

NORBORNENE DERIVATIVE; POLYSTYRENE; REAGENT; DYES, REAGENTS, INDICATORS, MARKERS AND BUFFERS; NORBORNANE DERIVATIVE;

CATALYSIS; CATALYST; CHEMICAL STRUCTURE; COMBINATORIAL CHEMISTRY; MITSUNOBU REACTION; PHASE TRANSITION; POLYMERIZATION; PURIFICATION; REVIEW; RING OPENING METATHESIS POLYMERIZATION; SYNTHESIS; ANIMAL; CHEMISTRY; DRUG DESIGN; HUMAN; METHODOLOGY; PHARMACEUTICS;

ANIMALS; COMBINATORIAL CHEMISTRY TECHNIQUES; DRUG DESIGN; HUMANS; INDICATORS AND REAGENTS; NORBORNANES; TECHNOLOGY, PHARMACEUTICAL;

EID: 0036654301     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (16)

1. Flynn DL, Devraj RV, Parlow JJ: Recent advances in polymer-assisted solution-phase chemical library synthesis and purification. Curr Opin Drug Discovery Dev (1998) 1:41-50.
2. Studer A, Hadida S, Ferritto R, Kim SY, Jeger P, Wipf P, Curran DP: Fluorous synthesis: A fluorous-phase strategy for improving separation efficiency in organic synthesis. Science (1997) 275:823-826.
3. Barrett AGM, Roberts RS, Schroder J: Impurity annihilation: Chromatography-free parallel Mitsunobu reactions. Org Lett (2000) 2:2999-3001. This is the first published disclosure of the use of in situ ROMP to polymermize norbornenyl-tagged reagent byproducts. The article specifically describes the post-reaction in situ ROMP of a norbornenyl-tagged DNAD byproduct from Mitsunobu reactions.
4. Hamed AM, Hanson PR: Capture-ROMP-release: Application for the synthesis of O-alkylhydroxylamines. Org Lett (2002) 4:1007-1010. This is the first phase-switching example that showcases norbornenyl-tagged hydroxylamine synthons in a multi-step reaction sequence. Norbornenyl-tagged monomeric substrates are separated from Mitsunobu reagents and byproducts by in situ polymerization, using a second-generation Grubbs catalyst.
5. Moore JD, Hamed AM, Henle J, Flynn DL, Hanson PR: Scavenge-ROMP-filter: A facile strategy to soluble scavenging via norbornenyl tagging of electrophilic reagents. Org Lett (2002) 4:1847-1849. This is the first published example of the use of in situ ROMP in a sequestration enabling reagent (SER) mode. Norbomenylmethanol is introduced as an SER during a purification protocol to scavenge excess electrophilic reactants. After derivatization, the norbomenyl-tagged electrophiles are removed from the reaction product by in situ ROMP.
6. Barrett AGM, Cramp SM, Roberts RS: ROMP-spheres: A novel high-loading polymer support using cross metathesis between vinyl polystyrene and norbornene derivatives. Org Lett (1999) 1:1083-1086.
7. Amauld T, Barrett AGM, Seifried R: ROMPgel supported allylboronate: A purification-free method for the preparation of homoallylic alcohols. Tetrahedron Lett (2001) 42:7899-7901. This paper describes the use of preformed ROMP-supported reactants, including allylation of aldehydes. The use of a strained diene (tetracyclo[6.2.1.1.0]dodeca-4,9-diene) as a ROMP cross-linking additive was also reported.
8. Barrett AGM, Cramp SM, Hennessy AJ, Procopiou PA, Roberts RS: Oxazole synthesis with minimal purification: Synthesis and application of a ROMPgel tosmic reagent. Org Lett (2001) 3:271-273.
9. Enholm EJ, Gallagher ME: Free radical reactions on soluble supports from ring-opening metathesis. Org Lett (2001) 3:3397-3399. This paper describes the use of preformed ROMP-supported substrates in radical reactions.
10. Enholm EJ, Cottone JS: Highly diastereoselective radical cyclizations on soluble ring opening metathesis supports. Org Lett (2001) 3:3959-3962.
11. Barrett AGM, Cramp SM, Roberts RS, Zecri FJ: Horner-Emmons synthesis with minimal purification using ROMPGEL: A novel high-loading matrix for supported reagents. Org Lett (1999) 1:579-582. This paper describes the use of preformed ROMP-supported Homer-Emmons reagents, including their use in olefination reactions. The utility of Barton's base in combinatorial chemistry is also discussed.
12. Amauld T, Barrett AGM, Cramp SM, Roberts RS, Zecri FJ: ROMPGEL scavengers: A high-loading supported anhydride for sequestering amines and hydrazines. Org Lett (2000) 2:2663-2666. This is the first published report on the use of a preformed ROMP-supported scavenging electrophile (anhydride) for the removal of excess nucleophiles from reaction mixtures.
13. Barrett AGM, Cramp SM, Roberts RS, Zecri FJ: A ROMPGEL-supported N-hydroxysuccinimide: A host of acylations with minimal purification. Org Lett (2000) 2:261-264.
14. Ball CP, Barrett AGM, Poitout LF, Smith ML, Thom ZE: Polymer backbone disassembly: Polymerisable templates and vanishing supports in high loading parallel synthesis. Chem Comm (1998):2453-2454. This is a novel paper that describes the phase-trafficking of reaction intermediates from solution (monomer)-phase to a ROMP polymer-phase, with final disassembly of the polymer backbone to afford monomeric 3-aza-8-oxabicylco[3.2.1]octanes.
15. Ahmed M, Barrett AGM, Braddock DC, Cramp SM, Procopiou PA: A recyclable 'boomerang' polymer-supported ruthenium catalyst for olefin metathesis. Tetrahedron Lett (1999) 40:8657-8662. This paper describes the use of a polystyrene-supported Grubbs catalyst. During catalytic cycle, the catalyst undergoes an initiation reaction by its metathesis reaction-release into the solution-phase. Propagation steps (ring-closing metathesis reactions) take place in solution-phase. A termination step involves recapture of the catalyst by vinyl polystyrene.
16. Ahmed M, Amauld T, Barrett AGM, Braddock DC, Procopiou PA: Second generation recyclable 'boomerang' polymer supported catalysts for olefin metathesis: Application of Arduengo carbene complexes. Synlett (2000):1007-1009. This paper offers an improvement in boomerang catalyst technology. The second-generation Grubbs IMes catalyst provides superior reaction kinetics and recyclability compared to the first-generation catalyst.