WO2002044193A1 - Procedimiento de obtencion de azaeritromicina - Google Patents
Procedimiento de obtencion de azaeritromicina Download PDFInfo
- Publication number
- WO2002044193A1 WO2002044193A1 PCT/ES2001/000452 ES0100452W WO0244193A1 WO 2002044193 A1 WO2002044193 A1 WO 2002044193A1 ES 0100452 W ES0100452 W ES 0100452W WO 0244193 A1 WO0244193 A1 WO 0244193A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- azaerythromycin
- catalyst
- obtaining
- hydrogenation
- deoxo
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
Definitions
- Azaerythromycin [formula I] (9-deoxo-9a-aza-9a-homoer ⁇ tromycin A) is a key intermediate for the synthesis of azithromycin [formula II] (9-deoxo-9a-aza-9a-methyl- 9a- homoerithromycin A).
- the present invention describes a process for its preparation from 6,9-iminoether [formula III] (9-deoxo-6-deoxy-6,9-epoxy-9,9a-didehydro-9a-aza omoerythromycin A) by hydrogenation low pressure catalytic
- Azithromycin is a macrolide antibiotic obtained by chemical synthesis from erythromycin A, it is more stable than this and has a broad spectrum of action that includes gram negative bacteria and intracellular microorganisms. It is described in patents US 4474768 and US 4517359.
- azithromycin is obtained by reductive methylation of azaerythromycin with a mixture of formic acid and aqueous formaldehyde under chloroform reflux (Eschweiler-Clarke reaction).
- azithromycin is obtained by oxidation of azaerythromycin to obtain the N-oxide derivative, followed by methylation and catalytic hydrogenation.
- erythromycin (9-deoxo-9a-aza-9a-homoerythromycin A) is described in US 4328334. Its synthesis from erythromycin A consists of several stages:
- EP 0879823 describes the synthesis of azithromycin from the iminoether directly in the same reactor.
- the yields range between 50 and 87%;
- hydrogenations are carried out at 60-70 bar using radius as catalyst and acetic acid as solvent.
- the object of the present invention is a new method of obtaining azaerithromycin that is simpler, cheaper and more industrializable than those described to date.
- 6,9-iminoether of erythromycin can be catalytically reduced at low pressure (less than 5 bar), after a pH adjustment with an appropriate acid and using alcohol solvents of 1 -3 carbon atoms or mixtures of these with water. Under the right conditions a high purity azaerythromycin is obtained with a good yield.
- the 6,9-iminoether of erythromycin A is catalytically reduced at low pressure (between 1-5 bar) to obtain azaerythromycin.
- the solvent for the reaction alcohols of 1-3 carbon atoms or mixtures thereof with water are used. It has been found that in these solvents and after a pH adjustment with a suitable acid (such as perchloric acid or hydrochloric acid), the reaction proceeds relatively quickly (3-4 hours) under mild temperature conditions (25 -45 ° C). Furthermore, in hydroalcoholic media, 6,9-iminoether does not evolve towards 9,11 -iminoether described in WO 94 26758. The product obtained had crystallized directly in basic aqueous solution. Heating the suspension between 35-45 ° C improves the crystallization performance.
- the solvents used are low molecular weight alcohols or mixtures thereof with water;
- the catalyst can be used several times, without detecting yield losses and / or noble metal;
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Saccharide Compounds (AREA)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2002220757A AU2002220757A1 (en) | 2000-11-30 | 2001-11-26 | Method for obtaining azaerythromycin |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ES200002858A ES2179756B1 (es) | 2000-11-30 | 2000-11-30 | Procedimiento de obtencion de azaeritromicina. |
ESP200002858 | 2000-11-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2002044193A1 true WO2002044193A1 (es) | 2002-06-06 |
Family
ID=8495813
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/ES2001/000452 WO2002044193A1 (es) | 2000-11-30 | 2001-11-26 | Procedimiento de obtencion de azaeritromicina |
Country Status (4)
Country | Link |
---|---|
AU (1) | AU2002220757A1 (pt) |
ES (1) | ES2179756B1 (pt) |
PT (1) | PT102564B (pt) |
WO (1) | WO2002044193A1 (pt) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007015265A2 (en) * | 2005-05-24 | 2007-02-08 | Kopran Research Laboratories Ltd | A process for preparing 6,9-imino ether |
WO2007017898A2 (en) * | 2005-05-24 | 2007-02-15 | Kopran Research Laboratories Ltd. | A process of recovery of pt/c catalyst in the preparation of azithromycin dihydrate |
CN1304407C (zh) * | 2004-09-03 | 2007-03-14 | 南京圣和药业有限公司 | 一种阿奇霉素的精制方法 |
WO2007029266A2 (en) * | 2005-05-24 | 2007-03-15 | Kopran Research Laboratories Ltd | A process for preparing 9-deoxo-9a-aza-9a-homoerythromycin a |
CN109575092A (zh) * | 2018-12-19 | 2019-04-05 | 宜昌东阳光药业股份有限公司 | 一种阿奇霉素重排杂质内酰胺的合成方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4328334A (en) * | 1979-04-02 | 1982-05-04 | Pliva Pharmaceutical And Chemical Works | 11-Aza-10-deoxo-10-dihydroerythromycin A and derivatives thereof as well as a process for their preparation |
WO1994026758A1 (en) * | 1993-05-19 | 1994-11-24 | Pfizer Inc. | Intermediate for azithromycin |
EP0879823A1 (en) * | 1997-05-19 | 1998-11-25 | Hovione Inter Ltd. | Preparation of azithromycin |
-
2000
- 2000-11-30 ES ES200002858A patent/ES2179756B1/es not_active Expired - Fee Related
-
2001
- 2001-02-12 PT PT10256401A patent/PT102564B/pt not_active IP Right Cessation
- 2001-11-26 WO PCT/ES2001/000452 patent/WO2002044193A1/es not_active Application Discontinuation
- 2001-11-26 AU AU2002220757A patent/AU2002220757A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4328334A (en) * | 1979-04-02 | 1982-05-04 | Pliva Pharmaceutical And Chemical Works | 11-Aza-10-deoxo-10-dihydroerythromycin A and derivatives thereof as well as a process for their preparation |
WO1994026758A1 (en) * | 1993-05-19 | 1994-11-24 | Pfizer Inc. | Intermediate for azithromycin |
EP0879823A1 (en) * | 1997-05-19 | 1998-11-25 | Hovione Inter Ltd. | Preparation of azithromycin |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1304407C (zh) * | 2004-09-03 | 2007-03-14 | 南京圣和药业有限公司 | 一种阿奇霉素的精制方法 |
WO2007015265A2 (en) * | 2005-05-24 | 2007-02-08 | Kopran Research Laboratories Ltd | A process for preparing 6,9-imino ether |
WO2007017898A2 (en) * | 2005-05-24 | 2007-02-15 | Kopran Research Laboratories Ltd. | A process of recovery of pt/c catalyst in the preparation of azithromycin dihydrate |
WO2007029266A2 (en) * | 2005-05-24 | 2007-03-15 | Kopran Research Laboratories Ltd | A process for preparing 9-deoxo-9a-aza-9a-homoerythromycin a |
WO2007017898A3 (en) * | 2005-05-24 | 2007-04-26 | Kopran Res Lab Ltd | A process of recovery of pt/c catalyst in the preparation of azithromycin dihydrate |
WO2007029266A3 (en) * | 2005-05-24 | 2007-12-06 | Kopran Res Lab Ltd | A process for preparing 9-deoxo-9a-aza-9a-homoerythromycin a |
WO2007015265A3 (en) * | 2005-05-24 | 2007-12-06 | Kopran Res Lab Ltd | A process for preparing 6,9-imino ether |
CN109575092A (zh) * | 2018-12-19 | 2019-04-05 | 宜昌东阳光药业股份有限公司 | 一种阿奇霉素重排杂质内酰胺的合成方法 |
CN109575092B (zh) * | 2018-12-19 | 2022-05-10 | 宜昌东阳光生化制药有限公司 | 一种阿奇霉素重排杂质内酰胺的合成方法 |
Also Published As
Publication number | Publication date |
---|---|
AU2002220757A1 (en) | 2002-06-11 |
ES2179756B1 (es) | 2004-10-01 |
ES2179756A1 (es) | 2003-01-16 |
PT102564A (pt) | 2002-05-31 |
PT102564B (pt) | 2004-07-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6013778A (en) | Process for the preparation of azithromycin | |
EP1077986B1 (en) | Improvements in macrolide production | |
HU199864B (en) | Process for production of derivatives of macrolide | |
EP2358732A1 (en) | Method of synthesizing macrolide compounds | |
ES2317561T3 (es) | Procedimiento de preparacion de la 4-amino-4'-demetil-4-desoxipodofilotoxina. | |
WO2002044193A1 (es) | Procedimiento de obtencion de azaeritromicina | |
US7205395B2 (en) | Process of preparing azithromycin and crystalline 9-deoxo-9a-aza-9a-homoerythromycin A hydrate used therein | |
JP3056035B2 (ja) | 9−デオキソ−9a−アザ−11−デオキシ−9a−ホモエリスロマイシンA 9a,11−環式カルバメート | |
PL155812B1 (en) | Method of obtaining novel derivatives of thylosine and 10,11,12,13-tetrahydrothylosine | |
WO2007015265A2 (en) | A process for preparing 6,9-imino ether | |
ES2260047T3 (es) | Proceso de etapa unica para la preparacion de 7,16-deoxi-2-aza-10-o-cladinosil-12-o-desosaminil-4,5-dihidroxi-6-etil-3,5,9,11,13,15-hexametilbiciclo(11.2.1)hexadeca-1(2)-en-ona y obtencion de una forma nueva de 9-deoxo-9a-metil-9a-homoeritromicina a. | |
SK37199A3 (en) | Compound 6-o-methyl erythromycin a 9-hydrazon, method for the preparation of 6-o-methyl erythromycin a 9-hydrazon and method for the preparation of 6-o-methyl erythromycin a 9-oxime | |
EP1490382A1 (en) | Process of preparing azithromycin and crystalline 9-deoxo-9a-aza-9a-homoerythromycin a hydrate used therein | |
DK172766B1 (da) | Derivater af det neutrale macrolid betegnet CP-63693 og farmaceutiske præparater indeholdende disse | |
WO2007029266A2 (en) | A process for preparing 9-deoxo-9a-aza-9a-homoerythromycin a | |
EP1887013A1 (en) | A process for preparing didanosine | |
EP1513857A1 (en) | Process for preparing high purity azithromycin | |
CN111574458A (zh) | 一种麦角硫因的合成方法 | |
WO2011054874A1 (en) | Method for the preparation of 2-amino-6-ethylbenzoic acid | |
MXPA98003916A (en) | Novedoso process for the preparation of azitromic | |
RU2144924C1 (ru) | Способ получения азитромицина и способы получения промежуточных соединений | |
EP1910393A2 (en) | A novel process for the preparation of didanosine using novel intermediates | |
SK282511B6 (sk) | Deriváty 12,13-epoxy-tylozínu a spôsob ich výroby | |
FI76098C (fi) | N-metyl-11-aza-10-deoxi-10 -dihydroerytromycin-n-oxidderivat, foerfarande foer framstaellning av dessa, vid foerfarandet anvaend mellanprodukt samt deras anvaendning vid framstaellning av n-metylderivat av 11-aza-10-deoxi-10 -dihydroerytromycin-a. | |
PL217775B1 (pl) | Sposób syntezy i izolacji N-demetylo-azytromycyny |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
32PN | Ep: public notification in the ep bulletin as address of the adressee cannot be established |
Free format text: NOTING LOSS OF RIGHTS PURSUANT TO RULE 69(1) EPC (EPO FORM 1205A SENT 01.10.03) |
|
122 | Ep: pct application non-entry in european phase | ||
NENP | Non-entry into the national phase |
Ref country code: JP |
|
WWW | Wipo information: withdrawn in national office |
Country of ref document: JP |