Professional Documents
Culture Documents
CONTENTs
Introduction Background Basic concepts Combinatorial synthesis Combinatorial synthesis & Traditional synthesis Techniques Isolation/Detection/Purification /Analysis Chemical Diversity & Liabrary Design Application & limitation Recent & Future Prospect References
history
Continuous improvement in various field In 1992 Bunin & Ellman demonstrate the synthesis of 1,4-Benzodiazepine
Introduce the method of generating small Non-peptide molecule i.e.Peptoid
First combinatorial chemistry experiment
1982
In
Avoid
3 4
5 6
Avoid
Possible
The anchor / linker e.g. Polystyrene resin , Tentagel resin , Polyacrylamide resin, Glass & ceramic beads .
Phe
Val
Ser
Gly
Gly Phe
Gly
Parallel synthesis What is the basic idea behind parallel synthesis ? The process where a single reaction product is produced in each reaction vessel.
Approach Houghton's Tea bag Procedure Automated Parallel Synthesis
Problems : # difficulty of removing unwanted material # purification at each step is necessary # other practical problem
Reagent
Excess
2 3 4 5 6
Easy Easy Suitable for few substance Expensive Mainly on - support - Linkers
Quantities of analyzed are very small Nondestructive / Allow recovery Rapid / Parallel analysis
Use hyphenated analytical technique e.g. HPLC-MS Chromatography Use IR / FTIR (computerized method) Use NMR / 2D-NMR / HPLC-NMR / CE-NMR MS / EI / MALDI-TOF / SIMS Use HPLC Supercritical Fluid Chromatography
Isolation i.e. Deconvlution - micromanipulation - recursive deconvolution - sequential release Structural determination of the active compd. - Tagging - Encoded sheets - Photolithography
It has been suggested that effectiveness of combinatorial chemistry could be improved by enhancing the chemical diversity of screening libraries .
Two more important features : - Chirality - Rigidity
Early work carried on peptides Next work done on peptoid Now researcher get concentrated on the heterocyclic combinatorial libraries e.g.- 1,4-Benzodiazepine All common reaction ,moisture sensitive & organometallic reactions e.g. Aldol reaction ,Dibal Reduction, Wittig reaction etc.
HIV-1 Integrase Block viral integration Human 5-HT 6 Serotonin Receptor Farnesyl transferase KDO-8-P Synthetase Antagonist, cognitive disorders Inhibition Inhibition, Antibacterial .
Smith-Kline Beecham
3 4
Agro-Chemical sector Advances in solution phase & Solid phase organic synthesis
Computational chemistry
QSPR
QSAR
References
Douglas R Henry ; Wilson & Gisvolds Textbook of Organic Medicinal chemistry ; 11th edition ;Lippincott William & Wilkins Publication ; 2004 ;Page No. 43-63 . Grahm L. Patrick ; Introduction To Medicinal Chemistry ; 2nd Edition ; Oxford publication ; 2003 ;Page No. 289-318 Gareth Thomas ; Medicinal Chemistry An Introduction ; Willey publication ; 2000 ; Page No. 69-90 . R.B.Silverman ; Organic chemistry of drug design & Drug Action ; 2nd Edition ;Elsevier publication ;2004 ; Page No.35-43 . www.netsci.org/science/Combichem/feature02.html www.biotech.nature.com ; NATURE BIOTECHNOLOGY ; Vol 18 ; Supplement 2000.