Chiral resolution by ch.vamsi anil krishna(Tinky)
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Transcript of Chiral resolution by ch.vamsi anil krishna(Tinky)
CHIRAL RESOLUTIONS AN INDUSTRIAL PROSPECTIVE
Presented by
Ch.Vamsi Anil Krishna(10AB1R0026)
Adderss:
Dept of Pharmaceutical Chemistry
Vignan Pharmacy College,Vadlamudi,
Guntur, Andhra Pradesh, India.
Contents: Introduction Resolution Methods Resolving agents Stereoselectivity of action Chiral drug sales Chiral BIOCKBUSTER DRUGS Conclusion
INTRODUCTION:
A chiral molecule and its mirror image are called a pair of
enantiomers. Enantiomers have identical chemical and physical
properties(IR, NMR, mp, mass spectra,…etc), except for their ability to
rotate plane-polarized light(+/-) by equal amounts but in opposite
directions.
RESOLUTION METHODS
Various techniques used:
Chromatography
Widely used in development laboratories
Applicable to >99% of small molecules at analytical scale
Used in manufacturing scale
Methods for Preparing Chiral Compounds
Chromatography
A small scaleseparation of thechiral compounds in labs.
Handling of chromatography
Kinetic Resolution
Evalution of an historical process(> 100 years)
Based upon different reaction rates of the isomers
Theoretically 100% yield
Technology applied on limited scale to date
Diastereomer Crystallisation
Most widely used technique in industry
Widely used in development
Cheap additives
Only one isomer recovered per stage
Resolving Agents
Stereoselectivity of action
SS
Dextro(+)
RR
Levo(-)
ENANTIOMERS
Out 100 drugs sold
in 1994:
Pure enantiomer
20%
Racemate
21%
No chiral
33%
Out 100 drugs sold
in 1997:
Pure enantiomer 30%
Racemate 9%
No chiral 57%
Racemic Mixture Single-enantiomer
Amphetamine(Benzedrine) Dextroamphetamine(Dexedrine)
Bupivacaine(Marcain) Levobupivacaine (Chirocaine)
Cetirizine(Zyrtec/ Reactine) Levocetirizine(Xyzal)
Citalopram(Celexa/ Cipramil) Escitalopram(Lexapro/ Cipralex)
Methylphinidate(Ritalin) Dexmethylphenidate(Focalin)
Racemic Mixture Single-enantiomer
Modafinil(Provigil) Armodafinil(Nuvigil)
Ofloxacin(Floxin) Levofloxacin(Levaquin)
Omeprazole(Prilosec) Esomeprazole(Nexium)
Salbutamol(Ventolin) Levalbuterol(Xopenex)
Zopiclone(Imovane) Eszopliclone(Lunesta)
Statical data: CHIRAL DRUG SALE SHOW NO SIGN OF SLOWING
$ MILLIONS 1998 1999 2000
Cardio vascular $21,906 $24,805 $26,012
Antibiotics 19,756 20,907 23,265
Cancer 8,006 9,420 13,360
Central Nervous System 7,027 8,592 13,720
Antiviral 6,131 7,540 13,446
Gastrointestinal 1,718 2,998 5,355
TOTAL $6,45,44 $74,262 $95,198
CHIRAL TECHNOLOGY IN COMMERCIALLY
Chiral technology is a rapidly
developing area
Chiral technology represents a huge commercial business opportunity that has yet to be fully realised
MARKET OF CHIRAL DRUGS
Single–enantiomer drug sales show a continuous growth worldwide
and many of the top selling drugs are marketed as single enantiomers
Annual sales of chiral drugs:
$133billion(2000), $172billion(2005)
Conclusion: It is necessary to consider the chiral nature of a com-pound in drug Research.
Enantiomers of all chiral bioactive molecules must be separated and tested.
The FDA and regulatory authorities in Europe, China, and Japan have provided guidelines indicating that only the active enantiomer of a chiral drug should be brought to market.
References:Chiral drug separation
Bingyun LiDonald T. Haynie Engineering and Physics, Bionano systems Engineering Labo Biomedical ratory, Center for Applied Physics Studies, Louisiana Tech University, Ruston, Louisiana, U.S.A
The impact of chiral technology on the pharmaceutical industry
ANDY RICHARDS & RAY McCAGUE
Acknowledgement:
This work was supported by
A.VISWANATH M.pharm (Ph.D)
Dept of Pharamaceutical chemisrty.
My beloved PRINCIPAL
Dr.P.SRINIVASA BABU
Thank you