Synthesis, molecular docking and dynamic studies of 3-cyano-6-hydroxy-5-pentaloxy N-Boc Cyclohexene as key intermediate for oseltamivir phosphate
A key intermediate for oseltamivir phosphate synthesis, compound 15 (3-cyano-6-hydroxy-5-pentaloxy-N-Boccyclohexene), was synthesized from inexpensive, commercially available 1,4-cyclohexadiene (4). The synthesis involved eight steps, sequentially introducing substituents onto a cyclohexene ring: An...
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Penerbit Universiti Kebangsaan Malaysia
2025
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| Online Access: | http://journalarticle.ukm.my/26323/1/SMS%207.pdf http://journalarticle.ukm.my/26323/ https://www.ukm.my/jsm/english_journals/vol54num9_2025/contentsVol54num9_2025.html |
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| author | Zurhana Mat Hussin, Najmah P.S Hasan, Fazni Susila Abd Ghani, Shaari Daud, Mohd Salleh Rofiee, Syahrul Imran, Mohd Tajudin Mohd Ali, |
| author_facet | Zurhana Mat Hussin, Najmah P.S Hasan, Fazni Susila Abd Ghani, Shaari Daud, Mohd Salleh Rofiee, Syahrul Imran, Mohd Tajudin Mohd Ali, |
| author_sort | Zurhana Mat Hussin, |
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| content_provider | Universiti Kebangsaan Malaysia |
| content_source | UKM Journal Article Repository |
| continent | Asia |
| country | Malaysia |
| description | A key intermediate for oseltamivir phosphate synthesis, compound 15 (3-cyano-6-hydroxy-5-pentaloxy-N-Boccyclohexene), was synthesized from inexpensive, commercially available 1,4-cyclohexadiene (4). The synthesis involved eight steps, sequentially introducing substituents onto a cyclohexene ring: An amino group at C1, hydroxy at C6, pentaloxy at C5, and cyano at C3. C1 amination was achieved via epoxidation and asymmetric ring opening using a salen complex and TMSN₃. The C6 hydroxy group was introduced via one-pot reduction and amine protection. C5 functionalization involved allylic oxidation (SeO₂/TBHP) and etherification with 3-pentanol. The C3 cyano group was formed via olefin epoxidation, TMSCN ring opening, and elimination. Molecular docking showed compound 15 had a binding energy of -7.14 kcal/ mol, comparable to oseltamivir (-8.5 kcal/mol), suggesting strong neuraminidase binding. A 200 ns molecular dynamics simulation confirmed complex stability, with RMSF analysis indicating stable interactions. The ADMET profile indicates that these compounds exhibit good drug-like properties, including high gastrointestinal (GI) absorption, good solubility, and no inhibition of CYP450 enzymes. |
| format | Article |
| id | my-ukm.journal.26323 |
| institution | Universiti Kebangsaan Malaysia |
| language | en |
| publishDate | 2025 |
| publisher | Penerbit Universiti Kebangsaan Malaysia |
| record_format | eprints |
| spelling | my-ukm.journal.263232026-01-08T04:58:33Z http://journalarticle.ukm.my/26323/ Synthesis, molecular docking and dynamic studies of 3-cyano-6-hydroxy-5-pentaloxy N-Boc Cyclohexene as key intermediate for oseltamivir phosphate Zurhana Mat Hussin, Najmah P.S Hasan, Fazni Susila Abd Ghani, Shaari Daud, Mohd Salleh Rofiee, Syahrul Imran, Mohd Tajudin Mohd Ali, A key intermediate for oseltamivir phosphate synthesis, compound 15 (3-cyano-6-hydroxy-5-pentaloxy-N-Boccyclohexene), was synthesized from inexpensive, commercially available 1,4-cyclohexadiene (4). The synthesis involved eight steps, sequentially introducing substituents onto a cyclohexene ring: An amino group at C1, hydroxy at C6, pentaloxy at C5, and cyano at C3. C1 amination was achieved via epoxidation and asymmetric ring opening using a salen complex and TMSN₃. The C6 hydroxy group was introduced via one-pot reduction and amine protection. C5 functionalization involved allylic oxidation (SeO₂/TBHP) and etherification with 3-pentanol. The C3 cyano group was formed via olefin epoxidation, TMSCN ring opening, and elimination. Molecular docking showed compound 15 had a binding energy of -7.14 kcal/ mol, comparable to oseltamivir (-8.5 kcal/mol), suggesting strong neuraminidase binding. A 200 ns molecular dynamics simulation confirmed complex stability, with RMSF analysis indicating stable interactions. The ADMET profile indicates that these compounds exhibit good drug-like properties, including high gastrointestinal (GI) absorption, good solubility, and no inhibition of CYP450 enzymes. Penerbit Universiti Kebangsaan Malaysia 2025 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/26323/1/SMS%207.pdf Zurhana Mat Hussin, and Najmah P.S Hasan, and Fazni Susila Abd Ghani, and Shaari Daud, and Mohd Salleh Rofiee, and Syahrul Imran, and Mohd Tajudin Mohd Ali, (2025) Synthesis, molecular docking and dynamic studies of 3-cyano-6-hydroxy-5-pentaloxy N-Boc Cyclohexene as key intermediate for oseltamivir phosphate. Sains Malaysiana, 54 (9). pp. 2185-2199. ISSN 0126-6039 https://www.ukm.my/jsm/english_journals/vol54num9_2025/contentsVol54num9_2025.html |
| spellingShingle | Zurhana Mat Hussin, Najmah P.S Hasan, Fazni Susila Abd Ghani, Shaari Daud, Mohd Salleh Rofiee, Syahrul Imran, Mohd Tajudin Mohd Ali, Synthesis, molecular docking and dynamic studies of 3-cyano-6-hydroxy-5-pentaloxy N-Boc Cyclohexene as key intermediate for oseltamivir phosphate |
| title | Synthesis, molecular docking and dynamic studies of 3-cyano-6-hydroxy-5-pentaloxy N-Boc Cyclohexene as key intermediate for oseltamivir phosphate |
| title_full | Synthesis, molecular docking and dynamic studies of 3-cyano-6-hydroxy-5-pentaloxy N-Boc Cyclohexene as key intermediate for oseltamivir phosphate |
| title_fullStr | Synthesis, molecular docking and dynamic studies of 3-cyano-6-hydroxy-5-pentaloxy N-Boc Cyclohexene as key intermediate for oseltamivir phosphate |
| title_full_unstemmed | Synthesis, molecular docking and dynamic studies of 3-cyano-6-hydroxy-5-pentaloxy N-Boc Cyclohexene as key intermediate for oseltamivir phosphate |
| title_short | Synthesis, molecular docking and dynamic studies of 3-cyano-6-hydroxy-5-pentaloxy N-Boc Cyclohexene as key intermediate for oseltamivir phosphate |
| title_sort | synthesis, molecular docking and dynamic studies of 3-cyano-6-hydroxy-5-pentaloxy n-boc cyclohexene as key intermediate for oseltamivir phosphate |
| url | http://journalarticle.ukm.my/26323/1/SMS%207.pdf http://journalarticle.ukm.my/26323/ https://www.ukm.my/jsm/english_journals/vol54num9_2025/contentsVol54num9_2025.html |
| url_provider | http://journalarticle.ukm.my/ |