Late-Stage Derivatization of Oleanolic Acid-Based Anti-HIV-1 Compounds
A 12-keto-type oleanolic acid derivative (4) has been identified as a potent anti-human immunodeficiency virus type-1 (HIV-1) compound that demonstrates synergistic effects with several types of HIV-1 neutralizing antibodies. In the present study, we used a common key synthetic intermediate to carry...
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| Veröffentlicht in: | Chemical & pharmaceutical bulletin 2024/03/25, Vol.72(3), pp.330-335 |
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| creator | Takeuchi, Reon Fujimoto, Junko Taguchi, Yoshinori Ide, Ryuji Kyan, Ryuji Sato, Kohei Mase, Nobuyuki Yokoyama, Masaru Harada, Shigeyoshi Narumi, Tetsuo |
| description | A 12-keto-type oleanolic acid derivative (4) has been identified as a potent anti-human immunodeficiency virus type-1 (HIV-1) compound that demonstrates synergistic effects with several types of HIV-1 neutralizing antibodies. In the present study, we used a common key synthetic intermediate to carry out the late-stage derivatization of an anti-HIV compound based on the chemical structure of a 12-keto-type oleanolic acid derivative. To execute this strategy, we designed a diketo-type oleanolic acid derivative (5) for chemoselective transformation, targeting the carboxy group and the hydroxyl group on the statine unit, as well as the 3-carbonyl group on the oleanolic acid unit, as orthogonal synthetic handles. We carried out four types of chemoselective transformations, leading to identification of the indole-type derivative (16) as a novel potent anti-HIV compound. In addition, further optimization of the β-hydroxyl group on the statine unit provided the R-4-isobutyl γ-amino acid-type derivative (6), which exhibited potent anti-HIV activity comparable to that of 4 but with reduced cytotoxicity. |
| doi_str_mv | 10.1248/cpb.c23-00891 |
| format | Article |
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In the present study, we used a common key synthetic intermediate to carry out the late-stage derivatization of an anti-HIV compound based on the chemical structure of a 12-keto-type oleanolic acid derivative. To execute this strategy, we designed a diketo-type oleanolic acid derivative (5) for chemoselective transformation, targeting the carboxy group and the hydroxyl group on the statine unit, as well as the 3-carbonyl group on the oleanolic acid unit, as orthogonal synthetic handles. We carried out four types of chemoselective transformations, leading to identification of the indole-type derivative (16) as a novel potent anti-HIV compound. In addition, further optimization of the β-hydroxyl group on the statine unit provided the R-4-isobutyl γ-amino acid-type derivative (6), which exhibited potent anti-HIV activity comparable to that of 4 but with reduced cytotoxicity.</description><identifier>ISSN: 0009-2363</identifier><identifier>EISSN: 1347-5223</identifier><identifier>DOI: 10.1248/cpb.c23-00891</identifier><identifier>PMID: 38522899</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>Amino acids ; Antibodies ; Antiviral activity ; Antiviral agents ; Carbonyl groups ; Carbonyls ; Cytotoxicity ; HIV ; Human immunodeficiency virus ; human immunodeficiency virus type-1 (HIV-1) entry inhibitor ; Hydroxyl groups ; late-stage derivatization ; Oleanolic acid ; Synergistic effect</subject><ispartof>Chemical and Pharmaceutical Bulletin, 2024/03/25, Vol.72(3), pp.330-335</ispartof><rights>2024 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c499t-752016e05dbf1b4edfaf18c79e94d2b1a0c086f2cfbd2f9cf11548e753c68d8e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38522899$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takeuchi, Reon</creatorcontrib><creatorcontrib>Fujimoto, Junko</creatorcontrib><creatorcontrib>Taguchi, Yoshinori</creatorcontrib><creatorcontrib>Ide, Ryuji</creatorcontrib><creatorcontrib>Kyan, Ryuji</creatorcontrib><creatorcontrib>Sato, Kohei</creatorcontrib><creatorcontrib>Mase, Nobuyuki</creatorcontrib><creatorcontrib>Yokoyama, Masaru</creatorcontrib><creatorcontrib>Harada, Shigeyoshi</creatorcontrib><creatorcontrib>Narumi, Tetsuo</creatorcontrib><title>Late-Stage Derivatization of Oleanolic Acid-Based Anti-HIV-1 Compounds</title><title>Chemical & pharmaceutical bulletin</title><addtitle>Chem. Pharm. Bull.</addtitle><description>A 12-keto-type oleanolic acid derivative (4) has been identified as a potent anti-human immunodeficiency virus type-1 (HIV-1) compound that demonstrates synergistic effects with several types of HIV-1 neutralizing antibodies. In the present study, we used a common key synthetic intermediate to carry out the late-stage derivatization of an anti-HIV compound based on the chemical structure of a 12-keto-type oleanolic acid derivative. To execute this strategy, we designed a diketo-type oleanolic acid derivative (5) for chemoselective transformation, targeting the carboxy group and the hydroxyl group on the statine unit, as well as the 3-carbonyl group on the oleanolic acid unit, as orthogonal synthetic handles. We carried out four types of chemoselective transformations, leading to identification of the indole-type derivative (16) as a novel potent anti-HIV compound. In addition, further optimization of the β-hydroxyl group on the statine unit provided the R-4-isobutyl γ-amino acid-type derivative (6), which exhibited potent anti-HIV activity comparable to that of 4 but with reduced cytotoxicity.</description><subject>Amino acids</subject><subject>Antibodies</subject><subject>Antiviral activity</subject><subject>Antiviral agents</subject><subject>Carbonyl groups</subject><subject>Carbonyls</subject><subject>Cytotoxicity</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>human immunodeficiency virus type-1 (HIV-1) entry inhibitor</subject><subject>Hydroxyl groups</subject><subject>late-stage derivatization</subject><subject>Oleanolic acid</subject><subject>Synergistic effect</subject><issn>0009-2363</issn><issn>1347-5223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNpd0M1LwzAcxvEgis6Xo1cpePESzUtfkuOcToWBB1-uIU1-0Y6umUkr6F9v5nSCh6aHfHgIX4SOKTmnLBcXZlmfG8YxIULSLTSiPK9wwRjfRiNCiMSMl3wP7cc4J4QVpOK7aI-LJISUIzSd6R7wQ69fILuC0LzrvvlMn-8y77L7FnTn28ZkY9NYfKkj2Gzc9Q2-vXvGNJv4xdIPnY2HaMfpNsLRz_8APU2vHye3eHZ_czcZz7DJpexxVTBCSyCFrR2tc7BOOypMJUHmltVUE0NE6ZhxtWVOGkdpkQuoCm5KYQXwA3S23l0G_zZA7NWiiQbaVnfgh6iYFEUlc1KwRE__0bkfQpdepzjhgpWUcZoUXisTfIwBnFqGZqHDh6JErQKrFFilwOo7cPInP6tDvQC70b9FE5iswTyuom6ADn1jWvieq5jiq2Mz-3f7qoOCjn8BEyWMzQ</recordid><startdate>20240325</startdate><enddate>20240325</enddate><creator>Takeuchi, Reon</creator><creator>Fujimoto, Junko</creator><creator>Taguchi, Yoshinori</creator><creator>Ide, Ryuji</creator><creator>Kyan, Ryuji</creator><creator>Sato, Kohei</creator><creator>Mase, Nobuyuki</creator><creator>Yokoyama, Masaru</creator><creator>Harada, Shigeyoshi</creator><creator>Narumi, Tetsuo</creator><general>The Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20240325</creationdate><title>Late-Stage Derivatization of Oleanolic Acid-Based Anti-HIV-1 Compounds</title><author>Takeuchi, Reon ; Fujimoto, Junko ; Taguchi, Yoshinori ; Ide, Ryuji ; Kyan, Ryuji ; Sato, Kohei ; Mase, Nobuyuki ; Yokoyama, Masaru ; Harada, Shigeyoshi ; Narumi, Tetsuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-752016e05dbf1b4edfaf18c79e94d2b1a0c086f2cfbd2f9cf11548e753c68d8e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Amino acids</topic><topic>Antibodies</topic><topic>Antiviral activity</topic><topic>Antiviral agents</topic><topic>Carbonyl groups</topic><topic>Carbonyls</topic><topic>Cytotoxicity</topic><topic>HIV</topic><topic>Human immunodeficiency virus</topic><topic>human immunodeficiency virus type-1 (HIV-1) entry inhibitor</topic><topic>Hydroxyl groups</topic><topic>late-stage derivatization</topic><topic>Oleanolic acid</topic><topic>Synergistic effect</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takeuchi, Reon</creatorcontrib><creatorcontrib>Fujimoto, Junko</creatorcontrib><creatorcontrib>Taguchi, Yoshinori</creatorcontrib><creatorcontrib>Ide, Ryuji</creatorcontrib><creatorcontrib>Kyan, Ryuji</creatorcontrib><creatorcontrib>Sato, Kohei</creatorcontrib><creatorcontrib>Mase, Nobuyuki</creatorcontrib><creatorcontrib>Yokoyama, Masaru</creatorcontrib><creatorcontrib>Harada, Shigeyoshi</creatorcontrib><creatorcontrib>Narumi, Tetsuo</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Chemical & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takeuchi, Reon</au><au>Fujimoto, Junko</au><au>Taguchi, Yoshinori</au><au>Ide, Ryuji</au><au>Kyan, Ryuji</au><au>Sato, Kohei</au><au>Mase, Nobuyuki</au><au>Yokoyama, Masaru</au><au>Harada, Shigeyoshi</au><au>Narumi, Tetsuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Late-Stage Derivatization of Oleanolic Acid-Based Anti-HIV-1 Compounds</atitle><jtitle>Chemical & pharmaceutical bulletin</jtitle><addtitle>Chem. 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We carried out four types of chemoselective transformations, leading to identification of the indole-type derivative (16) as a novel potent anti-HIV compound. In addition, further optimization of the β-hydroxyl group on the statine unit provided the R-4-isobutyl γ-amino acid-type derivative (6), which exhibited potent anti-HIV activity comparable to that of 4 but with reduced cytotoxicity.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>38522899</pmid><doi>10.1248/cpb.c23-00891</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino acids Antibodies Antiviral activity Antiviral agents Carbonyl groups Carbonyls Cytotoxicity HIV Human immunodeficiency virus human immunodeficiency virus type-1 (HIV-1) entry inhibitor Hydroxyl groups late-stage derivatization Oleanolic acid Synergistic effect |
| title | Late-Stage Derivatization of Oleanolic Acid-Based Anti-HIV-1 Compounds |
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