Development of Preparation for Key Intermediates of Medicines Using Rearrangements as Key Reactions.

以重排为关键反应制备关键药物中间体的开发。

基本信息

  • 批准号:
    05555244
  • 负责人:
  • 金额:
    $ 9.15万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Developmental Scientific Research (B)
  • 财政年份:
    1993
  • 资助国家:
    日本
  • 起止时间:
    1993 至 1995
  • 项目状态:
    已结题

项目摘要

Recently, (Z) -7beta- [2- (5-amino-1,2,4-thiadiazol-3-yl)-2- (alkoxyimino) acetamido] cephalosporins such as SCE2787 (cephazopran), E1040 and E1077 have been reported as clinically useful antibiotics having excellent antimicrobial activities. Their common acyl moiety at the C-7 position is corresponding to the Z-isomer (1) of 2- (5-amino-1,2,4-thiadiazol-3-yl) -2- (alkoxyimino) acetic acid. The E isomer is known to be not valuable for useful beta-lactam antibiotics, so far. Consequentyl, it was our intention to successfully develop a general method of entry into the Z-isomer by our own strategy, although several methods have been reported for the production of 1. The Z-isomer (1) has been prepared from the aminoisoxazoles through the skeletal rearrangement in several routes. Reaction of 3-amino-5-methoxyisoxazole with alkoxycarbonyl isothiocyanates gave methyl 2- (5-alkoxy carbonylamino-1,2,4-thiadiazol-3-yl) accetates, which were converted into the target compound 1 through the reaction of the corresponding keto ester with O-methylhydroxylamime. Compound 1 was prepared similarly from 3-aminoisoxa-zole. Also, O-methylation of 2-hydroxyimino-2- (5-methoxycarbonyl amino-1,2,4-thiazol-3-yl) acetate with methyl iodide or dimethyl sulfate in the presence of barium oxide and barium hydroxide octahydrate was found to afford exclusively the desired Z-isomer, which was led to 1.On the other hand, rataniaphenols are known to show strong antibiotic activities especially against B.gingivalis, and structurally, have a 2-phenylbenzofuran unit as their skeletons. Herein, the basic compound, 2-p-hydroxyphenylbenzofuran has been effectively synthesized from o-cresol through an ortho-toluate-carbanion rearrangement of the p-methoxybenzoate.
最近,已经报道了(Z)-7 β- [2-(5-氨基-1,2,4-噻二唑-3-基)-2-(烷氧基亚氨基)乙酰胺基]头孢菌素如SCE 2787(头孢唑仑)、E1040和E1077作为具有优异抗微生物活性的临床有用的抗生素。它们在C-7位的共同酰基部分对应于2-(5-氨基-1,2,4-噻二唑-3-基)-2-(烷氧基亚氨基)乙酸的Z-异构体(1)。到目前为止,已知E异构体对于有用的β-内酰胺抗生素没有价值。因此,我们的目的是通过我们自己的策略成功地开发进入Z-异构体的一般方法,尽管已经报道了几种用于生产1的方法。Z-异构体(1)是由氨基异恶唑通过骨架重排的几种途径制备的。3-氨基-5-甲氧基异恶唑与烷氧羰基异硫氰酸酯反应生成2-(5-烷氧羰基氨基-1,2,4-噻二唑-3-基)乙酸甲酯,再与相应的酮基酯和O-甲基羟胺反应生成目标化合物1。化合物1类似地由3-氨基异恶唑制备。此外,2-羟基亚氨基-2-甲基化发现在氧化钡和氢氧化钡八水合物存在下,(5-甲氧羰基氨基-1,2,4-噻唑-3-基)乙酸酯与甲基碘或硫酸二甲酯仅得到所需的Z-异构体,其导致1。另一方面,已知拉他尼酚显示出强的抗生素活性,特别是对牙龈B.gingivalis,并且在结构上,具有2-苯基苯并呋喃单元作为它们的骨架。本文以邻甲酚为原料,通过对甲氧基苯甲酸酯的邻甲苯甲酸酯-负碳离子重排反应,有效地合成了碱性化合物2-对羟基苯基苯并呋喃。

项目成果

期刊论文数量(13)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Kuniaki Tatsuta: "A practical preparation of (z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)acetic acid." Tetrahedron Letters. 34. 6423-6426 (1993)
Kuniaki Tatsuta:“(z)-2-(5-氨基-1,2,4-噻二唑-3-基)-2-(甲氧基亚氨基)乙酸的实际制备。”
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    0
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  • 通讯作者:
Kuniaki Tatsuta: "Total synthesis of chlorinated phenylpyrrole antibiotics,(+)- and (-)-neopyrrolomycins." Tetrahedron Letters. 34. 8443-8444 (1993)
Kuniaki Tatsuta:“氯化苯基吡咯抗生素,( )- 和 (-)-新吡咯霉素的全合成。”
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    0
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K.Tatsuta: "One-step synthesis of a pyroglutamyl peptidase inhibitor, pyrizinostatin, from an antibiotic, 2-methylfervenulone." J.Antibiot.47 (3). 389-390 (1994)
K.Tatsuta:“从抗生素 2-甲基阿维努酮一步合成焦谷氨酰肽酶抑制剂吡嗪他汀。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
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Kuniaki Tatsuta: "Synthesis and characterization of a 14-membered polyketide lactone." Tetarahedron Letters. 34. 4957-4960 (1993)
Kuniaki Tatsuta:“14 元聚酮内酯的合成和表征。”
  • DOI:
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    0
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  • 通讯作者:
Kuniaki Tatsuta: "Total synthesis of(+)-and(-)-neopyrrolomycins, chlorinated phenylpyrrole antibiotics." Bull. Chem. Soc. Jpn.67. 1449-1455 (1994)
Kuniaki Tatsuta:“( )-和(-)-新吡咯霉素、氯化苯基吡咯抗生素的全合成。”
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    0
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TATSUTA Kuniaki其他文献

TATSUTA Kuniaki的其他文献

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{{ truncateString('TATSUTA Kuniaki', 18)}}的其他基金

Total Syntheses of Bioactive Natural Products and Creation of Useful Substances.
生物活性天然产物的全合成和有用物质的创造。
  • 批准号:
    14205128
  • 财政年份:
    2002
  • 资助金额:
    $ 9.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Total Synthesis of Natural Products Possessing Multiple Bioactivities and Isolation of Their Activities
具有多种生物活性的天然产物的全合成及其活性分离
  • 批准号:
    10102010
  • 财政年份:
    1998
  • 资助金额:
    $ 9.15万
  • 项目类别:
    Grant-in-Aid for Specially Promoted Research
Synthesis and Development of Useful Glycosidase Inhibitors.
有用的糖苷酶抑制剂的合成和开发。
  • 批准号:
    08455419
  • 财政年份:
    1996
  • 资助金额:
    $ 9.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Bio-organic Synthesis of Several Antibiotics from Polyketide Lactone.
从聚酮内酯生物有机合成几种抗生素。
  • 批准号:
    05453133
  • 财政年份:
    1993
  • 资助金额:
    $ 9.15万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
Bio-Organic Studies on the Biosynthetic Pathway of Macrolide Antibiotics and the Application to the Synthesis of Useful Analogs
大环内酯类抗生素生物合成途径的生物有机研究及其在有用类似物合成中的应用
  • 批准号:
    02453088
  • 财政年份:
    1990
  • 资助金额:
    $ 9.15万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)

相似海外基金

Physicochemical analysis of metallo-beta-lactamase with improved catalytic efficiency for cephem antibiotics
提高头孢烯类抗生素催化效率的金属-β-内酰胺酶的理化分析
  • 批准号:
    26460037
  • 财政年份:
    2014
  • 资助金额:
    $ 9.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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