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Information and Communication Materials Lab.

1. 2. Wang resin (cleavage : TFA). Merrifield resin (cleavage : HF). Rink resin (cleavage : 10% TFA). Trityl Chloride resin (cleavage : AcOH). Photolabile resin (cleavage : hv). Si containing resin (cleavage : TBAF). Hanyang . University. Hanyang . University.

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Information and Communication Materials Lab.

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  2. 2 Wang resin (cleavage : TFA) Merrifield resin (cleavage : HF) Rink resin (cleavage : 10% TFA) Trityl Chloride resin (cleavage : AcOH) Photolabile resin (cleavage : hv) Si containing resin (cleavage : TBAF) Hanyang University Hanyang University • Anchor groups for linking the substrate to the solid support Polymeric Reagent 화학 반응이 진행하는 동안 reagent로 작용하는 functional group 을 포함하고 있는 polymer. Resins 일반적으로 polystyrene (1-2 % divinylbenzene 으로 crosslink 된 ) 이 많이 쓰임. 넓은 범위의 solvent polarity 에서 사용이 적합 resin의 mechanical damage 가 적음 resin의 interior area 가 넓음 Information and Communication Materials Lab. Information and Communication Materials Lab.

  3. 3 Hanyang University Hanyang University <Aromatic substitution> • Usages of Polymeric Reagents • : Solid-Phase Organic Synthesis(SPOS) • <Solid-Phase Organic Reactions : A Review of the Recent Literature, Pedro H. H. Hermkens, Harry C. J. Ottenheijm, David Rees, Tetrahedron, Vol. 52, No. 13, 4527-4554(1996)> • Amide Bond Formation • (natural biooligomer such as oligosaccharide, • oligopetide • unnatural biooligomer such as oligocarbamate, • small molecule such as benzodiazepine) • Aromatic Substitutions(Heck, Friedel-Craft) • Condensations(Claisen, Aldol, ) • Cycloaddition(Diels-Alder, ) • Olefination(Wittig Reaction) • Grignard reagents • Michael additions • Nucleophilic substitutions Information and Communication Materials Lab. Information and Communication Materials Lab.

  4. 4 Hanyang University Hanyang University <Condensation> <Cycloaddition> <Grignard reagent> Information and Communication Materials Lab. Information and Communication Materials Lab.

  5. 5 Hanyang University Hanyang University <Michael addition> <Nucleophilic substitution> Information and Communication Materials Lab. Information and Communication Materials Lab.

  6. Resin 을 유기용매에 swelling 후 첫번째 amino acid 와 반응. Filter 를 하면 미반응 amino acid 와 용매는 여과됨. 다시 swelling 후 deprotect. 두번째 amino acid 와 반응 위와 같은 과정을 반복. Resin 에 연결된 oligopeptide 를 HF 를 사용하여 떼어냄.

  7. 8 Hanyang University Hanyang University 2. Unnatural Biooligomer Peptide 구조가 체내에 있는 여러가지 효소에 의해 분해가 잘 일어남. 그러므로 peptidomestics( carbamate, urea, 등)을 사 용하여 peptide 의 단점을 보완. 효소에 의해 잘 분해되지 않으며 효소나 수용체를 억제할 수 있는 새로운 약품으로써의 가능성을 지님. (1) Oligocarbamate Charles. Y. Cho, Peter G. Schultz, et. al., Science, Vol. 261, 1303(1993) • Synthesis of oligocarbamate monomer Information and Communication Materials Lab. Information and Communication Materials Lab.

  8. 9 (2) Oligourea K. Burgess, D. S. Linthicum, and H. Shin, Angew. Chem. Int. Ed. Engl., 34, 907(1995) J. M. Kim et. al., Tetrahedron Lett., 37, 5305(1996) • Synthesis of oligourea Monomer

  9. 3. Small Molecule (1) Benzodiazepine B. A. Bunin and J. A. Ellman, J. Am. Chem. Soc., 114, 10997(1992) 10 Molecular weight 이 1000 이하인 화합물을 Small molecule 이라 함. 실제로 약효를 내는 화합물. Solid phase synthesis 의 장점을 이용하여 최근에 제약회사를 중심으로 급격히 확산. Fmoc으로 보호된 aminobenzophenone 유도체를 Piperidine으로 deprotect. Fmoc으로 보호된 amino acid fluoride와 반응. Piperidine을 사용 deprotect 후.5% acetic acid를 사용 60 oC로 반응. Alkylation을 통해 R4 를 도입 후 TFA로 resin에서 분리.

  10. Hanyang University Hanyang University Information and Communication Materials Lab. Information and Communication Materials Lab. 11 • 4.Oligosaccharide • J.Y.Roberge et. al., Science, 269, 202 (1995) • Hydroxy 기가 보호된 galactose glycal을 단량체로 사용. • Legin에 연결후 이중결합을 epoxydation으로 • 활성화 . • 두번째 단량체 합성. • 결합 – epoxidation을 반복. • Glucose로 마무리. Cleave and deprotect.

  11. 12 Hanyang University Hanyang University 5. Wittig reaction - disadvantage main product와 by-product(triphenylphosphine oxide)간의 분리가 어려움. 시약의 가격이 많이 듬 - alkene products by polymerica phosphine reagents high purity, 정량적인 수율을 얻을 수 있음. Information and Communication Materials Lab. Information and Communication Materials Lab.

  12. 13 Hanyang University Hanyang University <11C-Labelled Polymer-Bound Wittig Reagents in the Synthesis of 11C-Labelled Aromatic Alkenes> M. OGREN, K. HORNFELDT, K. J. FASTH AND B. LANGSTROM, Appl. Radiat. Iso., Vol. 46, No. 8, 771-775(1995)  Fast and efficient methods for the synthesis of 11C-labelled terminal and branched alkenes Information and Communication Materials Lab. Information and Communication Materials Lab.

  13. Hanyang University Hanyang University Information and Communication Materials Lab. Information and Communication Materials Lab.

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