GB856816A - Antibiotic substances related to novobiocin - Google Patents

Antibiotic substances related to novobiocin

Info

Publication number
GB856816A
GB856816A GB12421/57A GB1242157A GB856816A GB 856816 A GB856816 A GB 856816A GB 12421/57 A GB12421/57 A GB 12421/57A GB 1242157 A GB1242157 A GB 1242157A GB 856816 A GB856816 A GB 856816A
Authority
GB
United Kingdom
Prior art keywords
dihydroxycoumarin
prepared
chloride
formula
compound
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
Application number
GB12421/57A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck and Co Inc
Original Assignee
Merck and Co Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Merck and Co Inc filed Critical Merck and Co Inc
Publication of GB856816A publication Critical patent/GB856816A/en
Expired legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/04Heterocyclic radicals containing only oxygen as ring hetero atoms
    • C07H17/06Benzopyran radicals
    • C07H17/065Benzo[b]pyrans
    • C07H17/075Benzo[b]pyran-2-ones

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)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention comprises substituted coumarins of the general formula: <FORM:0856816/IV(b)/1> wherein R represents an acyl group, 8-desmethylnovobiocin of the formula: <FORM:0856816/IV(b)/2> 8-desmethyldihydronovobiocin of the formula: <FORM:0856816/IV(b)/3> 8-desmethylcyclonovobiocin of the formula: <FORM:0856816/IV(b)/4> and 7 - (3 - carbomyl - 4 - methylnovobioxyloxy) - acetomido - 4 - hydroxycoumarin of the formula: <FORM:0856816/IV(b)/5> and a process for the preparation of compounds of the general formula: <FORM:0856816/IV(b)/6> wherein R represents an acyl radical, by reacting a 3 - acylamino - 4, 7 - dihydroxy - coumarin with 2 - acyl - 3 - carbamyl - 4 - methyl - novobiosyl chloride in the presence of silver oxide and hydrolysing with a base the resulting product of the general formula: <FORM:0856816/IV(b)/7> to remove the R radical from the novobiosyl radical. Thus the specific compounds referred to above may be prepared by reacting in the presence of silver oxide 2-acyl-3-carbamyl-4-methylnovobiosyl chloride with 3-(3-[g , g -dimethylallyl] - 4 - acyloxybenzamido) - 4, 7 - dihydroxycoumarin, with 3 - (3 - [3 - methylbutyl] - 4 - acyloxybenzamido) -4, 7 - dihydroxycoumarin, with 3 - (2, 2 - dimethylchroman - 6 - carboxamido)-4, 7-dihydroxycoumarin, and with 3 - acetamido - 4, 7 - dihydroxycoumarin respectively, and subjecting the resulting reaction products to alkaline hydrolysis. The above processes may be modified in that (1) the 3-acylamino-4, 7-dihydroxycoumarin is prepared by treating 4, 7-dihydroxycoumarin with nitrous acid to form 2, 4-dioxo-7-hydroxy-3-oximinochroman, reducing this compound in the form of its hydrochloride with hydrogen in the presence of a noble metal catalyst to 3-amino-4, 7-dihydroxycoumarin and acylating this compound; (2) the 3-(3-[g , g -dimethylallyl] - 4 - acyloxybenzamido) - 4, 7 - dihydroxycoumarin is prepared by acylating 3-(g , g -dimethylallyl)-4-hydroxy-benzoic acid, treating the sodium salt of the acylated compound with oxalyl chloride in a solvent medium to form 3-(g , g -dimethylallyl)-4-acyloxybenzoyl chloride and acylating 3-amino-4, 7-dihydroxycoumarin with this compound; (3) the 3-(3-[3-methylbutyl]-4-acyloxybenzamido)-4, 7-dihydroxycoumarin is prepared by acylating 3-(3-methylbutyl)-4-hydroxybenzoic acid, treating the sodium salt of the acylated compound with oxalyl chloride in a solvent medium to form 3-(3-methylbutyl)-4-acyloxybenzoyl chloride, and acylating 3-amino-4, 7-dihydroxycoumarin with this compound; (4) the 3-(2, 2-dimethylchroman-6-carboxamido)-4, 7-dihydroxycoumarin is prepared by reacting 2, 2-dimethylchroman-6-carboxylate with thionyl chloride at room temperature to produce 2, 2-dimethylchroman-6-carbonylchloride and acylating 3-amino-4, 7- dihydroxycoumarin with this compound; and (5) the 3-acetamido-4, 7-dihydroxycoumarin is prepared by reacting 3-amino-4, 7-dihydroxycoumarin with acetic anhydride in the presence of pyridine to produce 4-acetoxy - 3 - acetamido - 7 - hydroxycoumarin and selectively hydrolysing this compond. Processes (2) to (5) may be modified in that 3-amino-4, 7-dihydroxycoumarin is prepared by treating 4, 7-dihydroxycoumarin with nitrous acid to form 2, 4-dioxo-7-hydroxy-3-oximinochroman and reducing this compound in the form of its hydrochloride with hydrogen in the presence of a noble metal catalyst and may be further modified in that 2-acyl-3-carbamyl-4-methyl-novobiosyl chloride is prepared by acylating 3-carbomyl-4-methylnovobiose which can be prepared by the process described and claimed in Specification 853,592 to produce 1, 2-diacyl-3-carbamyl-4-methylnovobiose and reacting this compound with hydrogen chloride under anhydrous conditions. In all the processes referred to above, coumarin compounds of the formula: <FORM:0856816/IV(b)/8> wherein R1 represents hydrogen or an acyl group, may exist and react as chromone compounds of the formula : <FORM:0856816/IV(b)/9> Detailed examples are given. 1, 2 - Diacyl - 3 - carbamyl - 4 - methyl - novobiose of the formula : <FORM:0856816/IV(b)/100> wherein R represents an acyl radical, is prepared by acylating 3-carbamyl-4-methyl-novobiose. 2-Acyl-3-carbamyl-4-methyl-novobiosyl chloride of the formula: <FORM:0856816/IV(b)/111> wherein R represents an acyl radical, is prepared by treating 1, 2-diacyl-3-carbamyl-4-methyl-novobiose with hydrogen chloride under anhydrous conditions Ethyl 3-(g , g -dimethylallyl)-4-hydroxybenzoate is prepared by reacting ethyl p-hydroxybenzoate and g , g -dimethylallyl bromide in the presence of sodium. 3-(g ,g - dimethylallyl)-4-hydroxybenzoic acid is prepared by hydrolysing the above ester. 3-(3-Methylbutyl)-4-hydroxybenzoic acid is prepared by hydrogenating ethyl 3-(g , g -dimethylallyl)-4-hydroxybenzoate in the presence of platinum oxide and hydrolysing the resulting ethyl 3-(3-methylbutyl)-4-hydroxybenzoate. Specifications 821,819 and 821,820 also are referred to.
GB12421/57A 1956-04-19 1957-04-16 Antibiotic substances related to novobiocin Expired GB856816A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US856816XA 1956-04-19 1956-04-19

Publications (1)

Publication Number Publication Date
GB856816A true GB856816A (en) 1960-12-21

Family

ID=22193243

Family Applications (1)

Application Number Title Priority Date Filing Date
GB12421/57A Expired GB856816A (en) 1956-04-19 1957-04-16 Antibiotic substances related to novobiocin

Country Status (1)

Country Link
GB (1) GB856816A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6701304B2 (en) * 1998-07-22 2004-03-02 Neopost Inc. Method and apparatus for postage label authentication

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6701304B2 (en) * 1998-07-22 2004-03-02 Neopost Inc. Method and apparatus for postage label authentication

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