GB1591696A - 3-nitro-rifamycins s and sv - Google Patents
3-nitro-rifamycins s and sv Download PDFInfo
- Publication number
- GB1591696A GB1591696A GB9294/78A GB929478A GB1591696A GB 1591696 A GB1591696 A GB 1591696A GB 9294/78 A GB9294/78 A GB 9294/78A GB 929478 A GB929478 A GB 929478A GB 1591696 A GB1591696 A GB 1591696A
- Authority
- GB
- United Kingdom
- Prior art keywords
- nitro
- rifamycins
- formula
- rifamycin
- coch3
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
- 229940081192 rifamycins Drugs 0.000 title claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 235000010288 sodium nitrite Nutrition 0.000 claims description 4
- 239000000010 aprotic solvent Substances 0.000 claims description 3
- 235000010323 ascorbic acid Nutrition 0.000 claims description 3
- 229960005070 ascorbic acid Drugs 0.000 claims description 3
- 239000011668 ascorbic acid Substances 0.000 claims description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229940099259 vaseline Drugs 0.000 description 2
- BTVYFIMKUHNOBZ-ZDHWWVNNSA-N Rifamycin S Natural products COC1C=COC2(C)Oc3c(C)c(O)c4C(=O)C(=CC(=O)c4c3C2=O)NC(=O)C(=C/C=C/C(C)C(O)C(C)C(O)C(C)C(OC(=O)C)C1C)C BTVYFIMKUHNOBZ-ZDHWWVNNSA-N 0.000 description 1
- BTVYFIMKUHNOBZ-ODRIEIDWSA-N Rifamycin S Chemical compound O=C1C(C(O)=C2C)=C3C(=O)C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O BTVYFIMKUHNOBZ-ODRIEIDWSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FHKPLLOSJHHKNU-INIZCTEOSA-N [(3S)-3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]-(oxan-4-yl)methanone Chemical compound C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N=1)O[C@@H]1CN(CC1)C(=O)C1CCOCC1)C FHKPLLOSJHHKNU-INIZCTEOSA-N 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229940109171 rifamycin sv Drugs 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
(54) 3-NITRO-RIFAMYCINS S AND SV
(71) We, ARCHIFAR LABORATORI CHIMICO FARMACOLOGICI
S.p.A., of Corso Verona 165 Rovereto (Trento), Italy, an Italian Joint Stock
Company, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- The present invention relates to new 3-nitro-rifamycins S and SV useful as starting compounds for the production of useful antibiotic substances.
More particularly the present invention concerns 3-nitro-rifamycins S of formula
and their hydroquinonic derivatives 3-nitro-rifamycins SV of formula
wherein Y is -H or -COCH3.
The 3-nitro-rifamycins S of formula (I) are obtained by reacting a 3-bromorifamycin S of formula
wherein Y is -H or -COCH3, with sodium nitrite in a dipolar aprotic solvent according to the scheme
at a temperature ranging from ambient temperature to 400C and isolating the so formed compound.
The compounds of formula (II) are obtained by mild reduction by means of ascorbic acid of the compounds of formula (I).
The 3-bromo-rifamycins S of formula (III) are per se well known and are described in German Patent published application DOS 2548128.
The compounds of formulae (I) and (II) per se do not have a practical interest as antibiotic substances, but they have shown to be suitable as intermediates or starting materials for the production of valuable antibiotic compounds.
To aid further understanding of the present invention, processes for obtaining such compounds will now be described in the following Examples.
The thin layer chromatographs referred to in the Examples as Rf are carried out on silica gel plates by using benzene:ethyl acetate:methanol (20:8:7 v/v) as eluent.
Infrared spectra are performed in Vaseline oil (Nujol) mull-Vaseline and
Nujol are Registered Trade Marks.
EXAMPLE 1
7.8 g of 3-bromo-rifamycin S are dissolved in 50 ml of N,N-dimethylformamide and are reacted with 0.82 g of sodium nitrite while stirring: the temperature rises spontaneously to 300C and stirring is continued at this temperature for 45 minutes.
The reaction mixture is diluted with 500 ml of dichloromethane and washed several times with water: the dichloromethane solution is dried over sodium sulfate and evaporated to dryness at reduced pressure.
The residue is crystallized from ethanol to give 4.8 g of pure 3-nitro-rifamycin
S as orange crystals.
Rf. 0.63 I.R. 3350, 1740, 1705, 1630, 1605, 1550, 1485, 1415, 1320, 1270, 1205, 1185,
1170, 1130, 1090, 1060, 970, 915 and 825 cm-'.
U.V. (CHCl3): 402 nm (E1%m 68); 272 nm (E1%m 336); 224 nm (E1%m 434).
P.M.R. (CDCl3), 8 (using TMS as internal standard): 0.24, 0.68, 0.87 and 0.99
(4 d, CH3-CH), 1.73 (s, CH3-13), 2.03 (s, CH3-30 and CH3-Coo), 2.35 (s, CH3-14), 3.13 (s,
CH3O), 4.73 (broad d, H-25), 5.03 (dd, H-28), 6.05-6.60 (m, H-17, H-18,
H-l9 and H-29), 8.38 (s, NH) and 12.44 (S, OH-8);
Elemental analysis: for C37H44N20,4 calc. V0 found % C 59.99 59.79
H 5.99 6.12
N 3.78 3.77
The same product is obtained using dimethyl sulfoxide as solvent.
EXAMPLE 2
8 g of 3-nitro-rifamycin S are dissolved in 320 ml of chloroform and, while stirring at room temperature, a solution of 8 g of ascorbic acid in 20 ml of water is added; stirring is continued until thin layer chromatography shows a complete reduction. The reaction mixture is decanted and the chloroform layer is separated and washed several times with water, then dried over magnesium sulfate and evaporated to dryness at reduced pressure; the residue is then crystallized from methanol to give 6.9 g of 3-nitro-rifamycin SV as orange crystals.
Rf. 0.31 I.R. 3350(b), 1740(sh), 1720, 1710(sh), 1665, 1655(sh), 1605, 1575(sh), 1550,
1340, 1320, 1290, 1250, 1220, 1170, 1125, 1100, 1060, 1050(sh), 1015, 970,
945, 890, 840 and 805 cm-'.
U.V. (HC1 N/10 in methanol): 436 nm (E1%m 102), 300 nm (E1%m 265).
EXAMPLE 3
3 g of 3-bromo-25-deacetyl rifamycin S are dissolved in 30 ml of N,N-dimethylformamide and reacted with 0.6 ml of triethylamine and 0.4 g of sodium nitrite at room temperature in a nitrogen atmosphere for 70 minutes; the reaction mixture is diluted with 50 ml of dichloromethane and washed with a 5% solution of citric acid several times; the dichloromethane solution is dried over sodium sulfate and evaporated to dryness and crystallized from methanol to give 1.8 g of pure 3-nitro25-deacetyl-rifamycin S.
Rf. 0.55
I.R. 3350, 1739, 1705, 1660, 1650, 1625, 1600, 1550, 1480, 1320, 1295, 1260,
1200, 1180, 1160, 1125, 1060, 970, 915 and 820 cm-'.
Claims (5)
1. 3-nitro-rifamycins S of formula
and their hydroquinonic derivatives, 3-nitro-rifamycins SV of formula
' ' TT *~nTT wherein Y is -H or -COCH3.
2. A process for the production of 3-nitro-rifamycins S of formula (I) according to claim 1, according to which a 3-bromo-rifamycin S of formula
wherein Y is -H or -COCH3, is reacted with sodium nitrite in a dipolar aprotic solvent at a temperature ranging from ambient temperature to 400C and isolating the so formed compound.
3. A process according to claim 2, wherein said dipolar aprotic solvent is selected from N,N-dimethylformamide and dimethyl sulfoxide.
4. A process for the production of 3-nitro-rifamycins SV of formula II according to claim 1, wherein 3-nitro-rifamycins S of formula (I) are submitted to mild reduction by means of ascorbic acid.
5. A process according to claim 2, 3 or 4 substantially as herein described.
Priority Applications (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9294/78A GB1591696A (en) | 1978-03-09 | 1978-03-09 | 3-nitro-rifamycins s and sv |
| IT20185/79A IT1113436B (en) | 1978-03-09 | 1979-02-14 | 3-NITRO-RIFAMICINE S AND SV |
| JP2090479A JPS54122296A (en) | 1978-03-09 | 1979-02-26 | 33nitroorifamycin s and sv and their manufacture |
| US06/016,080 US4217278A (en) | 1978-03-09 | 1979-02-28 | 3-Nitro-rifamycins S and SV |
| DE19792908855 DE2908855A1 (en) | 1978-03-09 | 1979-03-07 | 3-NITRO-RIFAMYCIN D AND SV AND THE PROCESS FOR THEIR PRODUCTION |
| FR7905943A FR2419292A1 (en) | 1978-03-09 | 1979-03-08 | 3-NITRO-RIFAMYCINS S AND SV |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9294/78A GB1591696A (en) | 1978-03-09 | 1978-03-09 | 3-nitro-rifamycins s and sv |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1591696A true GB1591696A (en) | 1981-06-24 |
Family
ID=9869202
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB9294/78A Expired GB1591696A (en) | 1978-03-09 | 1978-03-09 | 3-nitro-rifamycins s and sv |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPS54122296A (en) |
| DE (1) | DE2908855A1 (en) |
| FR (1) | FR2419292A1 (en) |
| GB (1) | GB1591696A (en) |
| IT (1) | IT1113436B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1090759B (en) * | 1977-11-29 | 1985-06-26 | Alfa Farmaceutici Spa | PROCEDURE FOR THE PREPARATION OF 3 IODINE AND 3 BROMO RIFAMICINA S |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1053787B (en) * | 1974-10-29 | 1981-10-10 | Pastori A | NITROGEN MACROLIDS AND THEIR PREPARATION |
-
1978
- 1978-03-09 GB GB9294/78A patent/GB1591696A/en not_active Expired
-
1979
- 1979-02-14 IT IT20185/79A patent/IT1113436B/en active
- 1979-02-26 JP JP2090479A patent/JPS54122296A/en active Pending
- 1979-03-07 DE DE19792908855 patent/DE2908855A1/en not_active Withdrawn
- 1979-03-08 FR FR7905943A patent/FR2419292A1/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| DE2908855A1 (en) | 1979-09-20 |
| IT7920185A0 (en) | 1979-02-14 |
| JPS54122296A (en) | 1979-09-21 |
| IT1113436B (en) | 1986-01-20 |
| FR2419292A1 (en) | 1979-10-05 |
| FR2419292B1 (en) | 1982-02-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed [section 19, patents act 1949] | ||
| 732 | Registration of transactions, instruments or events in the register (sect. 32/1977) | ||
| PCNP | Patent ceased through non-payment of renewal fee |