RS20050092A - Method for the separation of intermediates which may be used for the preparation of escitalopram - Google Patents

Method for the separation of intermediates which may be used for the preparation of escitalopram

Info

Publication number
RS20050092A
RS20050092A YUP-2005/0092A YUP20050092A RS20050092A RS 20050092 A RS20050092 A RS 20050092A YU P20050092 A YUP20050092 A YU P20050092A RS 20050092 A RS20050092 A RS 20050092A
Authority
RS
Serbia
Prior art keywords
preparation
escitalopram
intermediates
separation
formula
Prior art date
Application number
YUP-2005/0092A
Other languages
English (en)
Inventor
Naoaki Taoka
Takahisa Kato
Shogo Yamamoto
Takashi Yoshida
Toshihiro Takeda
Yasuyoshi Ueda
Hans Petersen
Robert Dancer
Haleh Ahmadian
Lars Ole Lyngso
Original Assignee
H.Lundbeck A/S.,
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by H.Lundbeck A/S., filed Critical H.Lundbeck A/S.,
Publication of RS20050092A publication Critical patent/RS20050092A/sr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B57/00—Separation of optically-active compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C255/53—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and hydroxy groups bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/32—Separation; Purification; Stabilisation; Use of additives
    • C07C253/34—Separation; Purification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/34—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring with cyano groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by unsaturated carbon chains
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C255/58—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
    • C07C255/59—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P13/00—Preparation of nitrogen-containing organic compounds
    • C12P13/001—Amines; Imines
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P13/00—Preparation of nitrogen-containing organic compounds
    • C12P13/002—Nitriles (-CN)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P13/00—Preparation of nitrogen-containing organic compounds
    • C12P13/008—Preparation of nitrogen-containing organic compounds containing a N-O bond, e.g. nitro (-NO2), nitroso (-NO)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P13/00—Preparation of nitrogen-containing organic compounds
    • C12P13/02—Amides, e.g. chloramphenicol or polyamides; Imides or polyimides; Urethanes, i.e. compounds comprising N-C=O structural element or polyurethanes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
    • C12P41/006—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by reactions involving C-N bonds, e.g. nitriles, amides, hydantoins, carbamates, lactames, transamination reactions, or keto group formation from racemic mixtures
    • C12P41/007—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by reactions involving C-N bonds, e.g. nitriles, amides, hydantoins, carbamates, lactames, transamination reactions, or keto group formation from racemic mixtures by reactions involving acyl derivatives of racemic amines
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/02—Preparation of oxygen-containing organic compounds containing a hydroxy group
    • C12P7/22—Preparation of oxygen-containing organic compounds containing a hydroxy group aromatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Hydrogenated Pyridines (AREA)

Abstract

Ovaj pronalazak se odnosi na novi postupak za dobijanje intermedijara diola sa formulom (II) i/ili suprotnog enantiomera aciliranog diola sa formulom (IV) korisnih za dobijanje escitaloprama obuhvatajući selektivnu enzimsku acilaciju ili deacilaciju.
YUP-2005/0092A 2002-08-12 2003-08-12 Method for the separation of intermediates which may be used for the preparation of escitalopram RS20050092A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DKPA200201201 2002-08-12
PCT/DK2003/000537 WO2004014821A1 (en) 2002-08-12 2003-08-12 Method for the separation of intermediates which may be used for the preparation of escitalopram

Publications (1)

Publication Number Publication Date
RS20050092A true RS20050092A (en) 2007-09-21

Family

ID=34717090

Family Applications (1)

Application Number Title Priority Date Filing Date
YUP-2005/0092A RS20050092A (en) 2002-08-12 2003-08-12 Method for the separation of intermediates which may be used for the preparation of escitalopram

Country Status (24)

Country Link
US (2) US20070129561A1 (sr)
EP (2) EP1534654A1 (sr)
JP (3) JP4694837B2 (sr)
KR (1) KR20050053618A (sr)
CN (2) CN100548939C (sr)
AR (1) AR040970A1 (sr)
AU (1) AU2003250321B2 (sr)
BR (1) BR0313114A (sr)
CA (1) CA2495118C (sr)
EA (1) EA011762B1 (sr)
HK (2) HK1131514A1 (sr)
IL (1) IL166319A0 (sr)
IS (1) IS7642A (sr)
ME (1) MEP1608A (sr)
MX (1) MXPA05001400A (sr)
NO (1) NO20051292L (sr)
NZ (1) NZ537785A (sr)
PE (1) PE20040991A1 (sr)
PL (1) PL374835A1 (sr)
RS (1) RS20050092A (sr)
TW (1) TWI306846B (sr)
UA (1) UA78840C2 (sr)
WO (1) WO2004014821A1 (sr)
ZA (1) ZA200500728B (sr)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TR200504022T1 (tr) * 2003-03-24 2006-08-21 Hetero Drugs Limited (S)-sitalopram oksalatın yeni sıvı kristal formları.
ES2228274B1 (es) * 2003-09-24 2006-06-01 Astur Pharma, S.A. Sintesis quimioenzimatica de (+)-citalopram y (-)-citalopram.
TWI339651B (en) * 2004-02-12 2011-04-01 Lundbeck & Co As H Method for the separation of intermediates which may be used for the preparation of escitalopram
WO2005084643A1 (en) * 2004-03-05 2005-09-15 H. Lundbeck A/S Crystalline composition containing escitalopram oxalate
US20050196453A1 (en) 2004-03-05 2005-09-08 H. Lundbeck A/S Crystalline composition containing escitalopram
ITMI20040717A1 (it) * 2004-04-09 2004-07-09 Adorkem Technology Spa Procedimento chemo-enzimatico per la preparazione dell'escitalopram
ITMI20041872A1 (it) * 2004-10-01 2005-01-01 Adorkem Technology Spa Processo per la preparazione di citalopram e di scitalopram
EP1736550A1 (en) * 2005-06-22 2006-12-27 Adorkem Technology SpA Chemoenzymatic process for the synthesis of escitalopram
GB0601286D0 (en) 2006-01-23 2006-03-01 Sandoz Ag Asymmetric synthesis
WO2008059514A2 (en) * 2006-07-31 2008-05-22 Cadila Healthcare Limited Process for preparing escitalopram
US7686946B2 (en) 2007-08-17 2010-03-30 Uop Llc Method of altering a feed to a reaction zone
CN100548974C (zh) * 2007-10-11 2009-10-14 浙江大学 西酞普兰中间体的萃取分离方法
WO2009094569A2 (en) * 2008-01-25 2009-07-30 Xenoport, Inc. Method for the enzymatic kinetic resolution of acyloxyalkyl thiocarbonates used for the synthesis of acyloxyalkyl carbamates
ITMI20120448A1 (it) 2012-01-30 2013-07-31 Carthesia Sas Composizione liofilizzata di escitalopram ossalato per somministrazione sublinguale
ES2554563B2 (es) * 2014-05-05 2016-08-16 Universidad De Sevilla Cepas bacterianas y sus usos en reacciones de acilación y/o desacilación
WO2017009866A1 (en) * 2015-07-11 2017-01-19 Ipca Laboratories Limited Novel recovery and recycling process of racemic 4-(4-dimethylamino)-1-(4'-fluorophenyl)-1-(hydroxybutyl)-3-(hydroxymethyl)-benzonitrile

Family Cites Families (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1526331A (en) 1976-01-14 1978-09-27 Kefalas As Phthalanes
GB8419963D0 (en) * 1984-08-06 1984-09-12 Lundbeck & Co As H Intermediate compound and method
EP0285287A3 (en) * 1987-03-23 1990-08-16 Smithkline Beecham Corporation 3-benzazepine compounds for use in treating gastrointestinal motility disorders
GB8814057D0 (en) * 1988-06-14 1988-07-20 Lundbeck & Co As H New enantiomers & their isolation
JP3097145B2 (ja) * 1991-02-27 2000-10-10 日産化学工業株式会社 コーリーラクトンジオールの光学分割方法
SE511903C2 (sv) 1996-06-28 1999-12-13 Sca Hygiene Prod Ab Absorberande alster innefattande en absorptionskropp med förbättrade vätskeinsläppsegenskaper
IT236075Y1 (it) 1997-06-26 2000-07-26 Emilio Brocco Macchina segatrice per la divisione in lastre di blocchi di materialelapideo
UA62985C2 (en) * 1997-11-10 2004-01-15 Lunnbeck As H A method for the preparation of citalopram
JP3813820B2 (ja) 1997-11-11 2006-08-23 ハー・ルンドベック・アクチエゼルスカベット シタロプラムの製造方法
JPH1129418A (ja) * 1998-06-12 1999-02-02 Takeda Chem Ind Ltd 農園芸用殺虫殺菌組成物
DE19832547A1 (de) * 1998-07-21 2000-01-27 Basf Ag Enzymhaltige Polymere
US6294571B1 (en) * 1998-09-11 2001-09-25 Independent Ink, Inc. Method for using neem extracts and derivatives for protecting wood and other cellulosic composites
WO2000023431A1 (en) 1998-10-20 2000-04-27 H. Lundbeck A/S Method for the preparation of citalopram
AR022329A1 (es) 1999-01-29 2002-09-04 Lundbeck & Co As H Metodo para la preparacion de 5-cianoftalida
CN1142926C (zh) * 1999-04-14 2004-03-24 H·隆德贝克有限公司 制备西酞普兰的方法
ITMI991581A1 (it) 1999-06-25 2001-01-15 Lundbeck & Co As H Metodo per la preparazione di citalopram
ITMI991579A1 (it) 1999-06-25 2001-01-15 Lundbeck & Co As H Metodo per la preparazione di citalopram
ITMI991486A1 (it) 1999-07-06 2001-01-06 Vis Farmaceutici S P A Processo per la sintesi di citalopram
PT1298124E (pt) * 1999-10-25 2007-05-31 Lundbeck & Co As H Método para a preparação de citalopram
EP1228056B1 (en) 1999-10-25 2004-09-22 H. Lundbeck A/S Method for the preparation of citalopram
NL1017415C1 (nl) 2000-02-24 2001-05-18 Lundbeck & Co As H Werkwijze voor de bereiding van Citalopram.
NL1017417C1 (nl) 2000-03-03 2001-03-16 Lundbeck & Co As H Werkwijze voor de bereiding van Citalopram.
GB0005477D0 (en) * 2000-03-07 2000-04-26 Resolution Chemicals Limited Process for the preparation of citalopram
NZ521201A (en) 2000-03-13 2004-02-27 H Method for the preparation of citalopram
EP1265881A1 (en) 2000-03-13 2002-12-18 H. Lundbeck A/S Stepwise alkylation of 5-substituted 1-(4-fluorophenyl)-1,3-dihydroisobenzofurans
IL151488A0 (en) 2000-03-14 2003-04-10 Lundbeck & Co As H Method for the preparation of citalopram
EA200200982A1 (ru) 2000-03-16 2003-02-27 Х.Лундбекк А/С Способ получения 5-циано-1-(4-фторфенил)-1,3-дигидроизобензофуранов
IL144816A (en) * 2000-08-18 2005-09-25 Lundbeck & Co As H Method for the preparation of citalopram
AR034612A1 (es) * 2001-06-25 2004-03-03 Lundbeck & Co As H Proceso para la preparacion del citalopram racemico y/o del s- o r-citalopram mediante la separacion de una mezcla de r- y s-citalopram
AR034759A1 (es) * 2001-07-13 2004-03-17 Lundbeck & Co As H Metodo para la preparacion de escitalopram
IL159326A0 (en) 2001-07-31 2004-06-01 Lundbeck & Co As H Crystalline composition containing escitalopram
IS7239A (is) * 2001-12-14 2004-04-29 H. Lundbeck A/S Aðferð til framleiðslu á essítalóprami
CA2381341A1 (en) * 2002-04-09 2003-10-09 Torcan Chemical Ltd. Process and intermediates for preparing escitalopram
CN1510024A (zh) * 2002-12-24 2004-07-07 北京德众万全药物技术开发有限公司 可用于制备西酞普兰(s)-对映异构体的新的化合物及其制备方法

Also Published As

Publication number Publication date
EA200500349A1 (ru) 2005-08-25
EP1534654A1 (en) 2005-06-01
ME00028B (me) 2010-02-10
NO20051292L (no) 2005-03-14
AU2003250321A1 (en) 2004-02-25
JP4694837B2 (ja) 2011-06-08
JP5520077B2 (ja) 2014-06-11
AU2003250321B2 (en) 2009-06-25
PL374835A1 (en) 2005-10-31
NZ537785A (en) 2006-12-22
JP2010150270A (ja) 2010-07-08
MXPA05001400A (es) 2005-04-28
PE20040991A1 (es) 2004-12-27
CA2495118A1 (en) 2004-02-19
TWI306846B (en) 2009-03-01
TW200418750A (en) 2004-10-01
HK1131514A1 (en) 2010-01-15
US20110065937A1 (en) 2011-03-17
CN101045664A (zh) 2007-10-03
CN1675144A (zh) 2005-09-28
CA2495118C (en) 2010-11-30
JP2011055842A (ja) 2011-03-24
EP2360150A1 (en) 2011-08-24
AR040970A1 (es) 2005-04-27
CN100548939C (zh) 2009-10-14
IL166319A0 (en) 2006-01-15
HK1083828A1 (en) 2006-07-14
EA011762B1 (ru) 2009-06-30
BR0313114A (pt) 2005-07-12
US20070129561A1 (en) 2007-06-07
US8067640B2 (en) 2011-11-29
UA78840C2 (en) 2007-04-25
KR20050053618A (ko) 2005-06-08
JP2005535322A (ja) 2005-11-24
CN101045664B (zh) 2011-06-15
MEP1608A (xx) 2010-02-10
WO2004014821A1 (en) 2004-02-19
ZA200500728B (en) 2006-07-26
IS7642A (is) 2005-01-12

Similar Documents

Publication Publication Date Title
NO20051292L (no) Fremgangsmate for separasjon av intermediater som kan anvendes for fremstillingen av escitalopram.
AU2002359522A8 (en) Compositions and methods of selective nucleic acid isolation
WO2004001062A3 (en) Multiplex nucleic acid reactions
HK1074059A1 (en) Enzymatic processes for the production of 4-substituted 3-hydroxybutyric acid derivatives
WO2005005679A3 (en) Super-hydrophobic surfaces, methods of their construction and uses therefor
WO2004071975A3 (en) Methods of making glass- ceramic particles
WO2004013294A3 (en) Method of producing non-recombinant bmp-2 and use thereof
AU2003238717A1 (en) POLYPEPTIDES HAVING Alpha- H-Alpha-AMINO ACID AMIDE RACEMASE ACTIVITY AND NUCLEIC ACIDS ENCODING THE SAME
WO2001016303A3 (de) Nucleinsäuren, die für enzymaktivitäten der spinosyn-biosynthese codieren
EP1557586A4 (en) METHOD FOR THE PRODUCTION OF TORSION DAMPERS
AU2003234900A1 (en) Method of preparing tetraacetylethylenediamine
PT2258847T (pt) Outras novas formas de moléculas de arn de interferência
ATE530639T1 (de) Mikroorganismen und verfahren zur verbesserten produktion von panthothenat
EP1483403A4 (en) IDENTIFICATION OF NUCLEOTIDE SEQUENCES BASED ON ENZYMATIC LIGATURES
AU2002361162A1 (en) Evanescence-based multiplex sequencing method
AU2003298492A8 (en) Enzymatic method for the isolation of dna from plant tissue
TWI347932B (en) Producing method of purified 2-cyanoacrylates
IL174219A0 (en) Enzymatic synthesis of enantiopure intermediates by means of cholesterolesterase from yeasts
PT1252327E (pt) Processo para a separacao enzimatica de racematos de derivados de aminometilaril-ciclo-hexanol
AU2002336564A1 (en) Method of enzyme production by microorganisms
WO2005065017A3 (en) Methods of inducing il-10 production
MXPA03005400A (es) Metodo para preparacion de 11 (12)-pentadecen-15-olidos.
AU2002321819A1 (en) Novel process for the production of pancreatic lipase inhibitor
ZA200202262B (en) Method of adhering coatings to substrates.
ITMI20030042A1 (it) Processo di sintesi enzimatica di antibiotici b lattamici.