The synthesis and characterization of analogs of the antimicrobial compound squalamine: 6β-hydroxy-3-aminosterols synthesized from hyodeoxycholic acid
Analogs of the aminosterol antimicrobial agent squalamine have been synthesized beginning from hyodeoxycholic acid. After carboxylic acid esterification and oxidation of both alcohol functions to ketones, the A/B ring junction was converted from cis to trans by acid-catalyzed isomerization. Differen...
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| Veröffentlicht in: | Steroids 1996-10, Vol.61 (10), p.565-571 |
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| creator | Jones, Stephen R. Kinney, William A. Zhang, Xuehai Jones, Lisa M. Selinsky, Barry S. |
| description | Analogs of the aminosterol antimicrobial agent
squalamine have been synthesized beginning from hyodeoxycholic acid. After carboxylic acid esterification and oxidation of both alcohol functions to ketones, the A/B ring junction was converted from
cis to
trans by acid-catalyzed isomerization. Different polyamines were added to the 3-keto group by reductive amination, yielding both the 3α and 3β addition products. The synthetic products exhibited potent, broad-spectrum antimicrobial activity similar to that of the parent compound. Changing the identity of the polyamine or the stereochemistry of addition has little effect upon antimicrobial activity but appears to change the selectivity of the agents. The analogs are synthesized with high yield from inexpensive starting materials and are promising alternatives to squalamine as potential antibiotics. |
| doi_str_mv | 10.1016/S0039-128X(96)00114-6 |
| format | Article |
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squalamine have been synthesized beginning from hyodeoxycholic acid. After carboxylic acid esterification and oxidation of both alcohol functions to ketones, the A/B ring junction was converted from
cis to
trans by acid-catalyzed isomerization. Different polyamines were added to the 3-keto group by reductive amination, yielding both the 3α and 3β addition products. The synthetic products exhibited potent, broad-spectrum antimicrobial activity similar to that of the parent compound. Changing the identity of the polyamine or the stereochemistry of addition has little effect upon antimicrobial activity but appears to change the selectivity of the agents. The analogs are synthesized with high yield from inexpensive starting materials and are promising alternatives to squalamine as potential antibiotics.</description><identifier>ISSN: 0039-128X</identifier><identifier>EISSN: 1878-5867</identifier><identifier>DOI: 10.1016/S0039-128X(96)00114-6</identifier><identifier>PMID: 8910969</identifier><identifier>CODEN: STEDAM</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>aminosterol ; Anti-Bacterial Agents - chemical synthesis ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; antimicrobials ; Biological and medical sciences ; Cholestanols - chemistry ; Cholestanols - pharmacology ; Cholic Acids - chemical synthesis ; Cholic Acids - chemistry ; Cholic Acids - pharmacology ; Deoxycholic Acid - chemistry ; Detergents - chemistry ; Ethylenediamines - chemical synthesis ; Ethylenediamines - chemistry ; Ethylenediamines - pharmacology ; hyodeoxycholic acid ; Medical sciences ; Microbial Sensitivity Tests ; Miscellaneous. Antibiotics with multiple activities ; Pharmacology. Drug treatments ; Pseudomonas aeruginosa - drug effects ; Spermine - analogs & derivatives ; Spermine - chemical synthesis ; Spermine - chemistry ; Spermine - pharmacology ; squalamine ; Staphylococcus aureus - drug effects ; Structure-Activity Relationship ; synthesis</subject><ispartof>Steroids, 1996-10, Vol.61 (10), p.565-571</ispartof><rights>1996</rights><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-508c5ca5e1996ff104d757b053e33b4f847332eb10920f8275a055e8789d06963</citedby><cites>FETCH-LOGICAL-c389t-508c5ca5e1996ff104d757b053e33b4f847332eb10920f8275a055e8789d06963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0039128X96001146$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2499189$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8910969$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jones, Stephen R.</creatorcontrib><creatorcontrib>Kinney, William A.</creatorcontrib><creatorcontrib>Zhang, Xuehai</creatorcontrib><creatorcontrib>Jones, Lisa M.</creatorcontrib><creatorcontrib>Selinsky, Barry S.</creatorcontrib><title>The synthesis and characterization of analogs of the antimicrobial compound squalamine: 6β-hydroxy-3-aminosterols synthesized from hyodeoxycholic acid</title><title>Steroids</title><addtitle>Steroids</addtitle><description>Analogs of the aminosterol antimicrobial agent
squalamine have been synthesized beginning from hyodeoxycholic acid. After carboxylic acid esterification and oxidation of both alcohol functions to ketones, the A/B ring junction was converted from
cis to
trans by acid-catalyzed isomerization. Different polyamines were added to the 3-keto group by reductive amination, yielding both the 3α and 3β addition products. The synthetic products exhibited potent, broad-spectrum antimicrobial activity similar to that of the parent compound. Changing the identity of the polyamine or the stereochemistry of addition has little effect upon antimicrobial activity but appears to change the selectivity of the agents. The analogs are synthesized with high yield from inexpensive starting materials and are promising alternatives to squalamine as potential antibiotics.</description><subject>aminosterol</subject><subject>Anti-Bacterial Agents - chemical synthesis</subject><subject>Anti-Bacterial Agents - chemistry</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>antimicrobials</subject><subject>Biological and medical sciences</subject><subject>Cholestanols - chemistry</subject><subject>Cholestanols - pharmacology</subject><subject>Cholic Acids - chemical synthesis</subject><subject>Cholic Acids - chemistry</subject><subject>Cholic Acids - pharmacology</subject><subject>Deoxycholic Acid - chemistry</subject><subject>Detergents - chemistry</subject><subject>Ethylenediamines - chemical synthesis</subject><subject>Ethylenediamines - chemistry</subject><subject>Ethylenediamines - pharmacology</subject><subject>hyodeoxycholic acid</subject><subject>Medical sciences</subject><subject>Microbial Sensitivity Tests</subject><subject>Miscellaneous. Antibiotics with multiple activities</subject><subject>Pharmacology. Drug treatments</subject><subject>Pseudomonas aeruginosa - drug effects</subject><subject>Spermine - analogs & derivatives</subject><subject>Spermine - chemical synthesis</subject><subject>Spermine - chemistry</subject><subject>Spermine - pharmacology</subject><subject>squalamine</subject><subject>Staphylococcus aureus - drug effects</subject><subject>Structure-Activity Relationship</subject><subject>synthesis</subject><issn>0039-128X</issn><issn>1878-5867</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2O1SAUx4nRjNfRR5iEhTG6qEIpFNwYM_ErmcSFY-KOUDhYTFvuQGvsvIjv4YP4TNK5N3frisM5v_P5R-iCkpeUUPHqCyFMVbSW354r8YIQSptK3EM7KltZcSna-2h3Qh6iRzn_IIQIpuozdCYVJUqoHfp93QPO6zT3kEPGZnLY9iYZO0MKt2YOccLRF78Z4ve8mYUs3zmMwabYBTNgG8d9XEpmvlnMYMYwwWss_v6p-tWl-GutWLU5Yy4145BP7W7BYZ_iiPs1Oiig7eMQLDY2uMfogTdDhifH9xx9ff_u-vJjdfX5w6fLt1eVZVLNFSfScms4UKWE95Q0ruVtRzgDxrrGy6ZlrIaubFsTL-uWG8I5lBMpR4QS7Bw9O9Tdp3izQJ71GLKFYTATxCXrVnIqlZQF5AewbJ1zAq_3KYwmrZoSvQmi7wTR27W1EvpOEL01uDg2WLoR3CnrqECJPz3GTbZm8MlMNuQTVjdKlQEK9uaAQTnGzwBJZxtgsuBCAjtrF8N_BvkH4Q6rsw</recordid><startdate>19961001</startdate><enddate>19961001</enddate><creator>Jones, Stephen R.</creator><creator>Kinney, William A.</creator><creator>Zhang, Xuehai</creator><creator>Jones, Lisa M.</creator><creator>Selinsky, Barry S.</creator><general>Elsevier Inc</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19961001</creationdate><title>The synthesis and characterization of analogs of the antimicrobial compound squalamine: 6β-hydroxy-3-aminosterols synthesized from hyodeoxycholic acid</title><author>Jones, Stephen R. ; Kinney, William A. ; Zhang, Xuehai ; Jones, Lisa M. ; Selinsky, Barry S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-508c5ca5e1996ff104d757b053e33b4f847332eb10920f8275a055e8789d06963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>aminosterol</topic><topic>Anti-Bacterial Agents - chemical synthesis</topic><topic>Anti-Bacterial Agents - chemistry</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>antimicrobials</topic><topic>Biological and medical sciences</topic><topic>Cholestanols - chemistry</topic><topic>Cholestanols - pharmacology</topic><topic>Cholic Acids - chemical synthesis</topic><topic>Cholic Acids - chemistry</topic><topic>Cholic Acids - pharmacology</topic><topic>Deoxycholic Acid - chemistry</topic><topic>Detergents - chemistry</topic><topic>Ethylenediamines - chemical synthesis</topic><topic>Ethylenediamines - chemistry</topic><topic>Ethylenediamines - pharmacology</topic><topic>hyodeoxycholic acid</topic><topic>Medical sciences</topic><topic>Microbial Sensitivity Tests</topic><topic>Miscellaneous. Antibiotics with multiple activities</topic><topic>Pharmacology. Drug treatments</topic><topic>Pseudomonas aeruginosa - drug effects</topic><topic>Spermine - analogs & derivatives</topic><topic>Spermine - chemical synthesis</topic><topic>Spermine - chemistry</topic><topic>Spermine - pharmacology</topic><topic>squalamine</topic><topic>Staphylococcus aureus - drug effects</topic><topic>Structure-Activity Relationship</topic><topic>synthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jones, Stephen R.</creatorcontrib><creatorcontrib>Kinney, William A.</creatorcontrib><creatorcontrib>Zhang, Xuehai</creatorcontrib><creatorcontrib>Jones, Lisa M.</creatorcontrib><creatorcontrib>Selinsky, Barry S.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Steroids</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jones, Stephen R.</au><au>Kinney, William A.</au><au>Zhang, Xuehai</au><au>Jones, Lisa M.</au><au>Selinsky, Barry S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The synthesis and characterization of analogs of the antimicrobial compound squalamine: 6β-hydroxy-3-aminosterols synthesized from hyodeoxycholic acid</atitle><jtitle>Steroids</jtitle><addtitle>Steroids</addtitle><date>1996-10-01</date><risdate>1996</risdate><volume>61</volume><issue>10</issue><spage>565</spage><epage>571</epage><pages>565-571</pages><issn>0039-128X</issn><eissn>1878-5867</eissn><coden>STEDAM</coden><abstract>Analogs of the aminosterol antimicrobial agent
squalamine have been synthesized beginning from hyodeoxycholic acid. After carboxylic acid esterification and oxidation of both alcohol functions to ketones, the A/B ring junction was converted from
cis to
trans by acid-catalyzed isomerization. Different polyamines were added to the 3-keto group by reductive amination, yielding both the 3α and 3β addition products. The synthetic products exhibited potent, broad-spectrum antimicrobial activity similar to that of the parent compound. Changing the identity of the polyamine or the stereochemistry of addition has little effect upon antimicrobial activity but appears to change the selectivity of the agents. The analogs are synthesized with high yield from inexpensive starting materials and are promising alternatives to squalamine as potential antibiotics.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>8910969</pmid><doi>10.1016/S0039-128X(96)00114-6</doi><tpages>7</tpages></addata></record> |
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| subjects | aminosterol Anti-Bacterial Agents - chemical synthesis Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology Antibiotics. Antiinfectious agents. Antiparasitic agents antimicrobials Biological and medical sciences Cholestanols - chemistry Cholestanols - pharmacology Cholic Acids - chemical synthesis Cholic Acids - chemistry Cholic Acids - pharmacology Deoxycholic Acid - chemistry Detergents - chemistry Ethylenediamines - chemical synthesis Ethylenediamines - chemistry Ethylenediamines - pharmacology hyodeoxycholic acid Medical sciences Microbial Sensitivity Tests Miscellaneous. Antibiotics with multiple activities Pharmacology. Drug treatments Pseudomonas aeruginosa - drug effects Spermine - analogs & derivatives Spermine - chemical synthesis Spermine - chemistry Spermine - pharmacology squalamine Staphylococcus aureus - drug effects Structure-Activity Relationship synthesis |
| title | The synthesis and characterization of analogs of the antimicrobial compound squalamine: 6β-hydroxy-3-aminosterols synthesized from hyodeoxycholic acid |
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