JPS6152160B2 - - Google Patents
Info
- Publication number
- JPS6152160B2 JPS6152160B2 JP5908677A JP5908677A JPS6152160B2 JP S6152160 B2 JPS6152160 B2 JP S6152160B2 JP 5908677 A JP5908677 A JP 5908677A JP 5908677 A JP5908677 A JP 5908677A JP S6152160 B2 JPS6152160 B2 JP S6152160B2
- Authority
- JP
- Japan
- Prior art keywords
- erythromycin
- dimethylformamide
- acetal
- value
- present
- 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
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical class O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 22
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- 229960003276 erythromycin Drugs 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 8
- 229930006677 Erythromycin A Natural products 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 230000000844 anti-bacterial effect Effects 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 238000000921 elemental analysis Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 4
- 235000019658 bitter taste Nutrition 0.000 description 4
- -1 erythromycin A enol Chemical class 0.000 description 4
- 241000192125 Firmicutes Species 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 241000187747 Streptomyces Species 0.000 description 2
- SWTCCCJQNPGXLQ-UHFFFAOYSA-N acetaldehyde di-n-butyl acetal Natural products CCCCOC(C)OCCCC SWTCCCJQNPGXLQ-UHFFFAOYSA-N 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 150000002084 enol ethers Chemical class 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- MDRYGXGPMGQHMC-UHFFFAOYSA-N 1,1-dimethoxy-n,n-dimethylmethanamine;n,n-dimethylformamide Chemical compound CN(C)C=O.COC(OC)N(C)C MDRYGXGPMGQHMC-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- JFVYXJKGJMUGRG-KJPZRSJGSA-N Erythromycin a enol ether Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C2=C(C)C[C@](O2)(C)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 JFVYXJKGJMUGRG-KJPZRSJGSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 238000002814 agar dilution Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- MBHINSULENHCMF-UHFFFAOYSA-N n,n-dimethylpropanamide Chemical compound CCC(=O)N(C)C MBHINSULENHCMF-UHFFFAOYSA-N 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 241001446247 uncultured actinomycete Species 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明はエリスロマイシンＡ誘導体に関し、更
に詳しくはエリスロマイシンＡ−11・12−アミド
アセタール誘導体またはエリスロマイシンＡエノ
ールエーテル−11・12−アミドアセタール誘導体
に関する。
エリスロマイシン群は放線菌ストレプトマイセ
ス エリスレウスの培養液中に産生されるマクロ
ライド抗生物質であつて、グラム陽性菌、グラム
陰性球菌に強い抗菌作用を示し、極めて有用では
あるが、経口内服薬として小児も繁用する関係上
その苦味が大きな障害となつていた。このため煩
瑣な反応を行なつて苦味のない化合物を得ても却
つて抗菌作用が減ずる場合が少なくなかつた。
本発明の目的はこれらの点を改良し、簡単な操
作によつて抗菌作用を減ずることなく、苦味のな
い新規のエリスロマイシンＡ誘導体を提供するこ
とにある。
本発明を以下詳細に説明する。
本発明の目的化合物は、
一般式
（式中、R1は水素原子または低級アルキル基を示
し、R2は水素原子または低級アルカノイル基を
示す。
〓〓は単一結合または二重結合を示し、〓〓が
単一結合を示すときはＡは水酸基を示し、〓〓が
二重結合を示すときはＡはその二重結合を形成す
る結合手の一を示す。）
で表わされるエリスロマイシンＡ誘導体またはそ
の塩である。
ここにおいて、低級アルキル基とは炭素原子数
が１〜３個のアルキル基であり、就中メチル基、
エチル基が好ましい。
低級アルカノイル基とは炭素原子数が２〜４個
のアルカノイル基であり、就中アセチル基が好ま
しい。
本発明の目的物は次の方法により合成される。
即ち、エリスロマイシンＡもしくはエリスロマイ
シンＡエノールエーテルまたはこれらの2′−０−
アシル誘導体をＮ・Ｎ−ジメチルホルムアミド、
ベンゼン、クロロホルムなどの溶媒中、Ｎ・Ｎ−
ジメチルホルムアミドジメチルアセタール；Ｎ・
Ｎ−ジメチルホルムアミドジブチルアセタール；
Ｎ・Ｎ−ジメチルアセトアミドジメチルアセター
ル；Ｎ・Ｎ−ジメチルプロピオンアミドジメチル
アセタールなどのアミドアセタールとともに室温
で撹拌して反応せしめるか、60〜100℃、望まし
くは70〜80℃で撹拌して反応せしめ、本発明の目
的物を得ることができる。
本発明の目的物の出発原料であるエリスロマイ
シンＡはストレプトマイセス エリスレウスの品
種を米国特許第2653899号公報記載の方法で培養
することによつて得られ、またそのエノールエー
テルはエクスペリエンテア第27巻第362ページ
（1971年）に記載のクラースらの方法により得る
ことができる。またこれらの2′−０−アシル誘導
体は常用のアシル化剤を用いて常法に従つて製造
することができる。
本発明の目的化合物はエリスロマイシンＡの有
する抗菌作用を減ずることなく、エリスロマイシ
ン群に特有の強い持続性のある苦味を著しく減少
し、経口内服薬として用いるのに極めて有利であ
る。また、小児は錠剤、カプセルなどを嚥下させ
るのが困難であるから、本発明の目的化合物は小
児用経口内服薬として特に有用である。
次に本発明の目的化合物のグラム陽性菌及びグ
ラム陰性菌に対する抗菌作用を示す試験例と実施
例を挙げて本発明を説明する。
試験例
本発明の目的化合物について寒天稀釈試験によ
つてそのグラム陽性菌及びグラム陰性菌に対する
抗菌試験を行なつた。
その試験結果をMIC値（最低阻止濃度）（mcg/
ml）で表わし、表に示した。
The present invention relates to erythromycin A derivatives, and more particularly to erythromycin A-11.12-amide acetal derivatives or erythromycin A enol ether-11.12-amide acetal derivatives. The erythromycin group is a macrolide antibiotic produced in the culture solution of the actinomycete Streptomyces erythreus.It has a strong antibacterial effect against gram-positive bacteria and gram-negative cocci, and is extremely useful. Due to its frequent use, its bitter taste was a major problem. For this reason, even if a compound without bitterness was obtained through complicated reactions, the antibacterial activity was often reduced. The object of the present invention is to improve these points and to provide a novel erythromycin A derivative which does not have a bitter taste and does not reduce its antibacterial action through simple operations. The present invention will be described in detail below. The object compound of the present invention has the general formula (In the formula, R 1 represents a hydrogen atom or a lower alkyl group, R 2 represents a hydrogen atom or a lower alkanoyl group. 〓〓 represents a single bond or a double bond, and 〓〓 represents a single bond. is an erythromycin A derivative or a salt thereof, represented by the following formula: A represents a hydroxyl group, and when 〓〓 represents a double bond, A represents one of the bonds forming the double bond. Here, the lower alkyl group is an alkyl group having 1 to 3 carbon atoms, especially a methyl group,
Ethyl group is preferred. The lower alkanoyl group is an alkanoyl group having 2 to 4 carbon atoms, and an acetyl group is particularly preferred. The object of the present invention is synthesized by the following method.
That is, erythromycin A or erythromycin A enol ether or their 2'-0-
The acyl derivative is N・N-dimethylformamide,
In solvents such as benzene and chloroform, N・N-
Dimethylformamide dimethyl acetal; N.
N-dimethylformamide dibutyl acetal;
N.N-dimethylacetamide dimethyl acetal; stirred and reacted with an amide acetal such as N.N-dimethylpropionamide dimethyl acetal at room temperature, or stirred and reacted at 60 to 100°C, preferably 70 to 80°C; The object of the present invention can be obtained. Erythromycin A, which is the starting material for the object of the present invention, is obtained by culturing Streptomyces erythreus varieties by the method described in U.S. Patent No. 2,653,899, and its enol ether is It can be obtained by the method of Claas et al., Vol. 362, 1971. Further, these 2'-0-acyl derivatives can be produced by a conventional method using a conventional acylating agent. The object compound of the present invention significantly reduces the strong and persistent bitter taste characteristic of the erythromycin group without reducing the antibacterial action of erythromycin A, and is extremely advantageous for use as an oral drug. Furthermore, since it is difficult for children to swallow tablets, capsules, etc., the object compound of the present invention is particularly useful as an oral medicine for children. Next, the present invention will be explained with reference to test examples and examples showing the antibacterial activity of the target compound of the present invention against Gram-positive bacteria and Gram-negative bacteria. Test Example The target compound of the present invention was subjected to an antibacterial test against Gram-positive bacteria and Gram-negative bacteria by an agar dilution test. The test results are calculated using the MIC value (minimum inhibitory concentration) (mcg/
ml) and shown in the table.
【表】
実施例 １
１ｇのエリスロマイシンＡを５mlのＮ・Ｎ−ジ
メチルホルムアミドに溶解し、0.5mlのＮ・Ｎ−
ジメチルホルムアミドに溶解した320mgのＮ・Ｎ
−ジメチルホルムアミドジメチルアセタールを０
℃で滴下後、室温で４日間撹拌した。この反応混
合物を300mlの酢酸エチルに注入し、これを400ml
の水で３回洗浄し、酢酸エチル層を無水硫酸マグ
ネシウムで乾燥し、酢酸エチルを留去して粗生成
物をアルミナカラムクロマトグラフイーに付し、
クロロホルムで溶出して精製し、白色ガラス状の
エリスロマイシンＡ−11・12−Ｎ・Ｎ−ジメチル
ホルムアミドアセタール810mgを得た。m.p.109
〜114℃
元素分析値：C40H72N2O13（分子量789.03）とし
て、
理論値(%)：Ｃ 60.89 Ｈ 9.19 Ｎ 3.55
実測値(%)：Ｃ 61.27 Ｈ 8.91 Ｎ 3.41
Ｍ・Ｓ・（実測値）：M+＝788
N.M.R.（CDCl3）：δ＝2.30（Ｓ、6H、Ｎ
（CH3）2）、2.39（Ｓ、6H、Ｎ（CH3）2）、3.36
（Ｓ、Ｈ、OCH3）
実施例 ２
0.78ｇの2′−０−アセチルエリスロマイシンＡ
を５mlのＮ・Ｎ−ジメチルホルムアミドに溶解
し、２mlのＮ・Ｎ−ジメチルホルムアミドに溶解
した400mgのＮ・Ｎ−ジメチルホルムアミドジブ
チルアセタールを０℃で滴下後、70℃で３時間撹
拌し、例１と同様に処理して粗生成物を得た。こ
の粗生成物をシリカゲルカラムクロマトグラフイ
ーに付し、クロロホルム−メタノール混液（25：
１）で溶出して精製し、色ガラス状の2′−０−ア
セチルエリスロマイシンＡ−11・12−Ｎ・Ｎ−ジ
メチルホルムアミドアセタール0.65ｇを得た。m.
p.119〜122℃
元素分析値：C42H74N2O14（分子量831.06）とし
て、
理論値(%)：Ｃ 60.70 Ｈ 8.98 Ｎ 3.37
実測値(%)：Ｃ 61.03 Ｈ 9.12 Ｎ 3.46
Ｍ・Ｓ・（実測値）：M+＝830
N.M.R.（CDCl3）：δ＝2.03（Ｓ、3H、
CH3COO）、2.24（Ｓ、6H、Ｎ（CH3）2）、2.35
（Ｓ、6H、Ｎ（CH3）2）、3.32（Ｓ、3H、
OCH3）
実施例 ３
0.5ｇの2′−０−アセチルエリスロマイシンＡ
エノールエーテルを15mlの無水ベンゼンに溶解
し、１mlの無水ベンゼンに溶解した160mgのＮ・
Ｎ−ジメチルホルムアミドジメチルアセタールを
室温で滴下し、24時間還流した後、実施例１と同
様に処理して粗生成物を得た。この粗生成物をシ
リカゲルカラムクロマトグラフイーに付し、クロ
ロホルム−メタノール混液（25：１）で溶出して
精製し、イソプロピルエーテルより再結晶せし
め、2′−０−アセチル−エリスロマイシンＡエノ
ールエーテル−11・12−Ｎ・Ｎ−ジメチルホルム
アミドアセタールの針状結晶0.33ｇを得た。m.
p.205〜207℃
元素分析値：C42H72N2O13（分子量813.05）とし
て、
理論値(%)：Ｃ 62.04 Ｈ 8.93 Ｎ 3.45
実測値(%)：Ｃ 62.08 Ｈ 8.96 Ｎ 3.39
Ｍ・Ｓ・（実測値）：M+＝812
N.M.R.（CDCl3）：δ＝1.56（Ｓ、3H、CH3）、
2.02（Ｓ、3H、CH3COO）、2.25（Ｓ、6H、Ｎ
（CH3）2）、2.35（Ｓ、6H、Ｎ（CH3）2）、3.32
（Ｓ、3H、OCH3）
実施例 ４
0.54ｇのエリスロマイシンＡを４mlのＮ・Ｎ−
ジメチルホルムアミドに溶解し、２mlのＮ・Ｎ−
ジメチルホルムアミドに溶解した200mgのＮ・Ｎ
−ジメチルアセトアミドジメチルアセタールを０
℃で滴下し、70℃で３時間撹拌後、実施例１と同
様に処理して粗生成物をアルミナカラムクロマト
グラフイーに付し、クロロホルム−ｎ−ヘキサン
混液（３：２）で溶出して精製し、白色ガラス状
のエリスロマイシンＡ−11・12−Ｎ・Ｎ−ジメチ
ルアセトアミドアセタール0.37ｇを得た。m.
p.114〜117℃
元素分析値：C41H74N2O13（分子量803.05）とし
て、
理論値(%)：Ｃ 61.32 Ｈ 9.29 Ｎ 3.49
実測値(%)：Ｃ 61.45 Ｈ 9.42 Ｎ 3.30
Ｍ・Ｓ・（実測値）：M+＝802
N.M.R.（CDCl3）：δ＝2.26（Ｓ、6H、Ｎ
（CH3）2）、2.28（Ｓ、6H、Ｎ（CH3）2）、3.30
（Ｓ、3H、OCH3）
実施例 ５
1.5ｇのエリスロマイシンＡを40mlのＮ・Ｎ−
ジメチルホルムアミドに溶解し、10mlのＮ・Ｎ−
ジメチルホルムアミドに溶解した1.5ｇのＮ・Ｎ
−ジメチルプロピオンアミドジメチルアセタール
を０℃で滴下し、80℃で11時間撹拌後、実施例３
と同様に処理して白色ガラス状のエリスロマイシ
ンＡ−11・12−Ｎ・Ｎ−ジメチルプロピオンアミ
ドアセタール0.92ｇを得た。m.p.107〜111℃
元素分析値：C42H76N2O13（分子量817.08）とし
て、
理論値(%) Ｃ 61.74 Ｈ 9.38 Ｎ 3.43
実測値(%) Ｃ 61.79 Ｈ 9.65 Ｎ 3.35
Ｍ・Ｓ・（実測値）：M+＝816
N.M.R.（CDCl3）：δ＝2.28（Ｓ、12H、２×Ｎ
（CH3）2）、3.30（Ｓ、3H、OCH3）[Table] Example 1 Dissolve 1 g of erythromycin A in 5 ml of N.N-dimethylformamide, and dissolve 0.5 ml of N.N-dimethylformamide.
320 mg of N.N dissolved in dimethylformamide
-Dimethylformamide dimethyl acetal 0
After the dropwise addition at °C, the mixture was stirred at room temperature for 4 days. This reaction mixture was poured into 300 ml of ethyl acetate, which was then added to 400 ml of
The ethyl acetate layer was dried over anhydrous magnesium sulfate, the ethyl acetate was distilled off, and the crude product was subjected to alumina column chromatography.
Purification was carried out by elution with chloroform to obtain 810 mg of white glassy erythromycin A-11.12-N.N-dimethylformamide acetal. mp109
~114℃ Elemental analysis value: C 40 H 72 N 2 O 13 (molecular weight 789.03) Theoretical value (%): C 60.89 H 9.19 N 3.55 Actual value (%): C 61.27 H 8.91 N 3.41 M・S・( Measured value): M + = 788 NMR (CDCl 3 ): δ = 2.30 (S, 6H, N
(CH 3 ) 2 ), 2.39 (S, 6H, N (CH 3 ) 2 ), 3.36
(S, H, OCH 3 ) Example 2 0.78 g of 2'-0-acetylerythromycin A
was dissolved in 5 ml of N.N-dimethylformamide, 400 mg of N.N-dimethylformamide dibutyl acetal dissolved in 2 ml of N.N-dimethylformamide was added dropwise at 0°C, and the mixture was stirred at 70°C for 3 hours. A crude product was obtained by treatment in the same manner as in 1. This crude product was subjected to silica gel column chromatography, and a chloroform-methanol mixture (25:
1) to obtain 0.65 g of 2'-0-acetylerythromycin A-11.12-N.N-dimethylformamide acetal in the form of a colored glass. m.
p.119-122℃ Elemental analysis value: C 42 H 74 N 2 O 14 (molecular weight 831.06) Theoretical value (%): C 60.70 H 8.98 N 3.37 Actual value (%): C 61.03 H 9.12 N 3.46 M・S. (actual value): M + = 830 NMR (CDCl 3 ): δ = 2.03 (S, 3H,
CH 3 COO), 2.24 (S, 6H, N (CH 3 ) 2 ), 2.35
(S, 6H, N(CH 3 ) 2 ), 3.32 (S, 3H,
OCH 3 ) Example 3 0.5 g of 2'-0-acetylerythromycin A
Enol ether was dissolved in 15 ml of anhydrous benzene and 160 mg of N.
N-dimethylformamide dimethyl acetal was added dropwise at room temperature, refluxed for 24 hours, and then treated in the same manner as in Example 1 to obtain a crude product. This crude product was purified by silica gel column chromatography, eluted with a chloroform-methanol mixture (25:1), recrystallized from isopropyl ether, and 2'-0-acetyl-erythromycin A enol ether-11 - Obtained 0.33 g of needle-like crystals of 12-N.N-dimethylformamide acetal. m.
p.205-207℃ Elemental analysis value: C 42 H 72 N 2 O 13 (molecular weight 813.05) Theoretical value (%): C 62.04 H 8.93 N 3.45 Actual value (%): C 62.08 H 8.96 N 3.39 M. S. (actual value): M + = 812 NMR (CDCl 3 ): δ = 1.56 (S, 3H, CH 3 ),
2.02 (S, 3H, CH 3 COO), 2.25 (S, 6H, N
(CH 3 ) 2 ), 2.35 (S, 6H, N (CH 3 ) 2 ), 3.32
(S, 3H, OCH 3 ) Example 4 0.54 g of erythromycin A was added to 4 ml of N・N-
Dissolve in dimethylformamide and add 2 ml of N・N-
200 mg N.N dissolved in dimethylformamide
-Dimethylacetamide dimethyl acetal 0
After stirring at 70°C for 3 hours, the crude product was treated in the same manner as in Example 1 and subjected to alumina column chromatography, eluting with a chloroform-n-hexane mixture (3:2). After purification, 0.37 g of white glassy erythromycin A-11.12-N.N-dimethylacetamide acetal was obtained. m.
p.114-117℃ Elemental analysis value: C 41 H 74 N 2 O 13 (molecular weight 803.05) Theoretical value (%): C 61.32 H 9.29 N 3.49 Actual value (%): C 61.45 H 9.42 N 3.30 M・S. (actual value): M + = 802 NMR (CDCl 3 ): δ = 2.26 (S, 6H, N
(CH 3 ) 2 ), 2.28 (S, 6H, N (CH 3 ) 2 ), 3.30
(S, 3H, OCH 3 ) Example 5 1.5 g of erythromycin A was added to 40 ml of N・N-
Dissolve in dimethylformamide and add 10 ml of N・N-
1.5 g of N.N dissolved in dimethylformamide
-Dimethylpropionamide dimethyl acetal was added dropwise at 0°C, and after stirring at 80°C for 11 hours, Example 3
0.92 g of white glassy erythromycin A-11.12-N.N-dimethylpropionamide acetal was obtained in the same manner as above. mp107～111℃ Elemental analysis value: C 42 H 76 N 2 O 13 (molecular weight 817.08) Theoretical value (%) C 61.74 H 9.38 N 3.43 Actual value (%) C 61.79 H 9.65 N 3.35 M・S・(actual measurement) value): M + = 816 NMR (CDCl 3 ): δ = 2.28 (S, 12H, 2 x N
(CH 3 ) 2 ), 3.30 (S, 3H, OCH 3 )
Claims (1)
し、R2は水素原子または低級アルカノイル基を
示す。 〓〓は単一結合または二重結合を示し、〓〓が
単一結合を示すときはＡは水酸基を示し、〓〓が
二重結合を示すときはＡはその二重結合を形成す
る結合手の一を示す。） で表わされるエリスロマイシンＡ誘導体またはそ
の塩。[Claims] 1. General formula (In the formula, R 1 represents a hydrogen atom or a lower alkyl group, R 2 represents a hydrogen atom or a lower alkanoyl group. 〓〓 represents a single bond or a double bond, and 〓〓 represents a single bond. An erythromycin A derivative or a salt thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5908677A JPS53144589A (en) | 1977-05-21 | 1977-05-21 | Erythromycin a derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5908677A JPS53144589A (en) | 1977-05-21 | 1977-05-21 | Erythromycin a derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS53144589A JPS53144589A (en) | 1978-12-15 |
| JPS6152160B2 true JPS6152160B2 (en) | 1986-11-12 |
Family
ID=13103169
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5908677A Granted JPS53144589A (en) | 1977-05-21 | 1977-05-21 | Erythromycin a derivatives |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS53144589A (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0056291B1 (en) * | 1981-01-09 | 1986-01-08 | Pierrel S.p.A. | Novel semisynthetic macrolidic antibiotics, microbiological processes for their preparation and related microorganism, novel intermediate compounds for their preparation and related pharmaceutical compositions containing them |
| DE3689758T2 (en) * | 1985-08-31 | 1994-08-18 | Kitasato Inst | Erythromycin derivative and process for its preparation. |
| WO1992006991A1 (en) * | 1990-10-15 | 1992-04-30 | Taisho Pharmaceutical Co., Ltd. | 2'-modified erythromycin or derivative thereof |
-
1977
- 1977-05-21 JP JP5908677A patent/JPS53144589A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS53144589A (en) | 1978-12-15 |
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