JPS5919120B2 - Method for producing nitrosourea compounds - Google Patents
Method for producing nitrosourea compoundsInfo
- Publication number
- JPS5919120B2 JPS5919120B2 JP15766275A JP15766275A JPS5919120B2 JP S5919120 B2 JPS5919120 B2 JP S5919120B2 JP 15766275 A JP15766275 A JP 15766275A JP 15766275 A JP15766275 A JP 15766275A JP S5919120 B2 JPS5919120 B2 JP S5919120B2
- Authority
- JP
- Japan
- Prior art keywords
- chloroethyl
- methyl
- producing
- nitrosouride
- reaction
- 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
Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
この発明はメチル 2−〔3−(2−クロロエチル)一
3−ニトロソウレイド〕−2・ 6−ジデオキシーグル
コピラノシツドの製造法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing methyl 2-[3-(2-chloroethyl)-3-nitrosouride]-2.6-dideoxyglucopyranoside.
本発明者は、従来より種々の糖化合物の合成を行つて来
たが、メチル 2−〔3−(2−クロロエチル)一3−
ニトロソウレイド〕−2・ 6−ジデオキシーグルコピ
ラノシツドが低毒性でかつ強力な抗腫瘍作用、特に抗白
血病作用を有することを発見し、この発明を完成させた
。したがつて、この発明は、メチル N−カルバミルー
N’一(2−クロロエチル)−6−デオキシーグルコサ
ミニドをニトロソ化することを特徴とするメチル 2−
〔3−(2−クロロエチル)一3−ニトロソウレイド〕
−2・ 6−ジデオキシーグルコピラノシツドの製造法
を提供するものである。The present inventor has previously synthesized various sugar compounds, including methyl 2-[3-(2-chloroethyl)-3-
The present invention was completed based on the discovery that nitrosouride]-2,6-dideoxyglucopyranoside has low toxicity and strong antitumor activity, particularly antileukemia activity. Therefore, the present invention provides methyl 2-carbamyl-N'-(2-chloroethyl)-6-deoxy-glucosaminide, which is characterized in that it is nitrosated.
[3-(2-chloroethyl)-3-nitrosouride]
A method for producing -2.6-dideoxyglucopyranoside is provided.
この発明において使用される出発物質であるメチル N
−カルバミルー N’−(2−クロロエチル)−6−デ
オキシーグルコサミニドは新規物質であり、たとえばメ
チル N−カルバミル−市−(2−クロロエチル)−6
−デオキシ−β−D−グルコサミニドはメチル N−ベ
ンジルオキシカルボニルー D−グルコサミニド〔A)
ノイベルガー(Neuberger)ら; J、Che
m、Soc、、122(1939)の方法により製造〕
にトシルクロライドを反応させて6位をトシル化し、次
いで残余の水酸基をアセチル基で保護し、さらにトシル
オキシ基をヨードで置換してヨード体とした後、水素添
加を行つて脱ヨード化し、次いで順次アセチル基、ベン
ジルオキシカルボニル基を常法で脱離した後、2−クロ
ルエチルイソシアネートを反応させることによつて製造
することができる。Methyl N, the starting material used in this invention
-Carbamyl N'-(2-chloroethyl)-6-deoxyglucosaminide is a new substance, for example methyl N-carbamyl-(2-chloroethyl)-6
-Deoxy-β-D-glucosaminide is methyl N-benzyloxycarbonyl D-glucosaminide [A]
Neuberger et al; J, Che
Manufactured by the method of M. Soc., 122 (1939)]
was reacted with tosyl chloride to tosylate the 6-position, then the remaining hydroxyl group was protected with an acetyl group, and the tosyloxy group was further substituted with iodine to form an iodo compound, followed by deiodination by hydrogenation, and then sequentially It can be produced by removing the acetyl group and benzyloxycarbonyl group by a conventional method and then reacting with 2-chloroethyl isocyanate.
本発明の方法を実施するに当つて、ニトロソ化反応はニ
トロソ化剤としてアルカリ金属亜硝酸塩、Ξ酸化窒素、
四酸化窒素を使用して実施するのがよい。アルカリ金属
亜硝酸塩としては亜硝酸ナトリウム、亜硝酸カリウムな
どが適当である。反応は−10℃〜30℃の温度で行わ
れ、反応は酸性(pH1〜3)で行うのが好ましい。反
応時間は1〜12時間が適当である。反応溶媒は水、ギ
酸、酢酸、プロピオン酸などの低級脂肪族カルボン酸が
好ましい。In carrying out the method of the present invention, the nitrosation reaction is carried out using an alkali metal nitrite, Ξnitric oxide,
This is preferably carried out using nitrogen tetroxide. Suitable alkali metal nitrites include sodium nitrite and potassium nitrite. The reaction is carried out at a temperature of -10°C to 30°C, and preferably the reaction is carried out under acidic conditions (pH 1 to 3). A suitable reaction time is 1 to 12 hours. The reaction solvent is preferably water, or a lower aliphatic carboxylic acid such as formic acid, acetic acid, or propionic acid.
反応終了後、必要に応じて陽イオン交換樹脂を使用して
精製し、凍結乾燥等を行つた後に適当な有機溶媒を使用
して再結晶を行い純品を得る。After completion of the reaction, if necessary, the product is purified using a cation exchange resin, freeze-dried, etc., and then recrystallized using an appropriate organic solvent to obtain a pure product.
かく得られるメチル 2−〔3−(2−クロロエチル)
一3−ニトロソウレイド〕−2・ 6−ジデオキシーグ
ルコピラノシツドは文献未収載の新規物質であつて抗白
血病、抗腫瘍作用などを示すほか、他の医薬品の製造中
間体として重要である。また、この化合物をピリジン、
無水酢酸の混液で反応を行わせると対応するアセチル体
を得ることができる(アセチル体の製造例は参考例とし
て掲げた)。次に実施例により本発明をさらに詳細に説
明する。The thus obtained methyl 2-[3-(2-chloroethyl)
[13-Nitrosouride]-2.6-dideoxyglucopyranoside is a new substance that has not been described in any literature and exhibits anti-leukemic and anti-tumor effects, and is also important as an intermediate in the production of other pharmaceuticals. In addition, this compound can be used as pyridine,
When the reaction is carried out with a mixture of acetic anhydride, the corresponding acetyl compound can be obtained (the production example of the acetyl compound is listed as a reference example). Next, the present invention will be explained in more detail with reference to Examples.
実施例
メチル 2−〔3 −( 2 −クロロエチル)−3−
ニトロソウレイド〕− 2 ・ 6 −ジデオキシ−β
−D−グルコピラノシツドの製造メチル N−カルバミ
ル−N−( 2 −クロロエチル)−6−デオキシ−β
− D−グルコサミニド306mfi7( 1.08ミ
リモル)をギ酸4ゴに溶解し、亜硝酸ナ゛トリウム14
9W1f7(2.16ミリモル)を徐々に加えて氷冷下
反応させる。Example methyl 2-[3-(2-chloroethyl)-3-
Nitrosouride]-2/6-dideoxy-β
-Production of D-glucopyranoside Methyl N-carbamyl-N-(2-chloroethyl)-6-deoxy-β
- Dissolve 306 mfi7 (1.08 mmol) of D-glucosaminide in 4 g of formic acid and add 14 g of sodium nitrite.
9W1f7 (2.16 mmol) was gradually added and reacted under ice cooling.
1時間30分後、淡黄色の結晶が析出する。After 1 hour and 30 minutes, pale yellow crystals precipitate.
結晶をろ過し、エタノールで洗浄し、1937nf7を
得る。P過をアンバーラィトIR−120(H+)9m
1で処理後、減圧濃縮して得られる残渣をエタノールで
ダイジエストし、78W19を得た。総収量271W1
f7( 71.8%)。Mp:163−163.5℃(
分解)〔α〕w:一 29.2゜(Cl.O、ピリジン
)IR(Cm−1 ):1705(CO)、1540(
NH)、.1500(N−NO) *Pmr(60MH
zピリジン− D5):δ1.62(D.、3、J6.
OHz)、C−CH3)δ3.57( S.、3、0−
CH3)δ9.54( D.、1、J7.5Hz,.C
−NH)元素分析値(ClOHl8N3O6Clについ
て):実験値:C) 38.37;H) 5.64;N
) 13.36;C1、11.53%計算値:C) 3
8.53;H) 5.82;N) 13.48;Cl)
11.37%参考例
メチル 3・4−ジ一o−アセチル− 2−〔3−(
2 −クロロエチル)− 3 −ニトロソウレイド〕−
2 ・ 6 −ジデオキシ−β− D−グルコピラノ
シツドの製造メチル 2−〔3 −( 2 −クロロエ
チル)−3−ニトロソウレイド〕− 2 ・ 6 −ジ
デオキシ−β−D−グルコピラノシツドグルコサミニド
67my(0.169ミリモル)をピリジンー無水酢酸
にて、常法によりアセチル化し、反応液を減圧留去し、
メタノールー水( 1:3 )で沈澱させる。Filter the crystals and wash with ethanol to obtain 1937nf7. Amber light IR-120 (H+) 9m
After treatment with 1, the residue obtained by concentration under reduced pressure was digested with ethanol to obtain 78W19. Total yield 271W1
f7 (71.8%). Mp: 163-163.5℃ (
decomposition) [α] w: - 29.2° (Cl.O, pyridine) IR (Cm-1): 1705 (CO), 1540 (
NH),. 1500 (N-NO) *Pmr (60MH
zPyridine-D5): δ1.62 (D., 3, J6.
OHz), C-CH3) δ3.57 (S., 3, 0-
CH3) δ9.54 (D., 1, J7.5Hz,.C
-NH) Elemental analysis value (for ClOHl8N3O6Cl): Experimental value: C) 38.37; H) 5.64; N
) 13.36; C1, 11.53% Calculated value: C) 3
8.53;H) 5.82;N) 13.48;Cl)
11.37% Reference example Methyl 3,4-di-o-acetyl-2-[3-(
2-chloroethyl)- 3-nitrosouride]-
Production of 2.6-dideoxy-β-D-glucopyranoside Methyl 2-[3-(2-chloroethyl)-3-nitrosouride]-2.6-dideoxy-β-D-glucopyranoside glucosamini Acetylate 67my (0.169 mmol) with pyridine-acetic anhydride in a conventional manner, and evaporate the reaction solution under reduced pressure.
Precipitate with methanol-water (1:3).
メチル3・4−ジ一0−アセチル− 2−〔3 −(
2 −クロロエチル)−3−ニトロソウレイド〕−2・
6−ジデオキシ−β− D−グルコピラノシツド7 1
.6Tnf7( 84.2%)を得た。Mp:117−
118℃(分解)〔α〕v:+ 41.6゜(Cl.O
)クロロホルム)工R(CnL−1):3350(NH
)、1740)1710( CO)、1545(NH)
、1495(N−NO)
Pmr( 60MHzCDC13):
δ1.28(d)3、J6.OHz,.C−CH3)δ
1.97(s)3、COCル)δ2.03( S,3、
COCH3)
δ3.49( s) 3、0C馬)Methyl 3,4-di-0-acetyl-2-[3-(
2-chloroethyl)-3-nitrosouride]-2.
6-dideoxy-β-D-glucopyranoside 7 1
.. 6Tnf7 (84.2%) was obtained. Mp:117-
118°C (decomposition) [α]v: + 41.6° (Cl.O
) Chloroform) Engineering R (CnL-1): 3350 (NH
), 1740) 1710 (CO), 1545 (NH)
, 1495(N-NO) Pmr (60MHzCDC13): δ1.28(d)3, J6. OHz,. C-CH3)δ
1.97(s)3, COCle) δ2.03(S,3,
COCH3) δ3.49 (s) 3,0C horse)
Claims (1)
)−6−デオキシ−グルコサミニドをニトロソ化するこ
とを特徴とするメチル2−〔3−(2−クロロエチル)
−3−ニトロソウレイド〕−2・6−ジデオキシ−グル
コピラノシツドの製造法。[Scope of Claims] 1. Methyl 2-[3-(2-chloroethyl), which is characterized by nitrosating methyl N-carbamyl-N'-(2-chloroethyl)-6-deoxy-glucosaminide.
-3-Nitrosouride] A method for producing -2,6-dideoxy-glucopyranoside.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP15766275A JPS5919120B2 (en) | 1975-12-30 | 1975-12-30 | Method for producing nitrosourea compounds |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP15766275A JPS5919120B2 (en) | 1975-12-30 | 1975-12-30 | Method for producing nitrosourea compounds |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS5283418A JPS5283418A (en) | 1977-07-12 |
JPS5919120B2 true JPS5919120B2 (en) | 1984-05-02 |
Family
ID=15654624
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP15766275A Expired JPS5919120B2 (en) | 1975-12-30 | 1975-12-30 | Method for producing nitrosourea compounds |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS5919120B2 (en) |
-
1975
- 1975-12-30 JP JP15766275A patent/JPS5919120B2/en not_active Expired
Also Published As
Publication number | Publication date |
---|---|
JPS5283418A (en) | 1977-07-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US3994966A (en) | Chelating agents | |
JPS60246393A (en) | Novel preparation of etoposide | |
JPH0240660B2 (en) | ||
JPH0250908B2 (en) | ||
JPS5919120B2 (en) | Method for producing nitrosourea compounds | |
WO1998056750A1 (en) | A process for the preparation of diacerein | |
JP2510586B2 (en) | Process for producing 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta (b) quinoline | |
JPS62185069A (en) | Production of oxiracetam | |
JP3257830B2 (en) | Novel thiophene derivatives, their production and use | |
JPS5854159B2 (en) | nitrosoniyosoyuudoutainoshinkiseizohou | |
JPH01131194A (en) | Production of pregnano (17 alpha, 16 alpha-d) oxazoline derivative | |
JPS5967252A (en) | Preparation of optically active beta-aminoisobutyric acid and its derivative | |
JPS604835B2 (en) | Manufacturing method of neothramycin | |
JPS6039264B2 (en) | Method for producing 3-amino-2-hydroxy-4-p-hydroxyphenylbutanoylleucine and its derivatives | |
CH467245A (en) | Process for the preparation of esters of tetracycline, 7-chlorotetracycline and 5-hydroxytetracycline | |
JP2815438B2 (en) | Purification method of 1,2-bis (nicotinamide) propane | |
SU443035A1 (en) | Method for preparing 1- (4-deoxy- - erythropentapyranosyl) -benzimidazole | |
JPS6139316B2 (en) | ||
JPH09255644A (en) | Production of adipic acid dihydrazide | |
US4045453A (en) | Method for producing 5-nitro-2-furfuryl acetate | |
US667381A (en) | Xanthin homologue and process of making same. | |
JPS59219300A (en) | Sucrose nitrosourea derivative | |
JPH02282345A (en) | Production of 2,4,5-trifluorobenzoic acid | |
JPS6317869A (en) | Production of 2-lower alkyl-4-amino-5-formylpyrimidine | |
JPH01143894A (en) | Production of 2',3'-dideoxynucleoside derivative |