Enantiomeric synthesis of carbocyclic d-4′-C-methylribonucleosides as potential antiviral agents |
| |
| Institution: | 1. Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China;2. Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China;1. Department of Chemistry, University of the West Indies, St. Augustine, Trinidad and Tobago;2. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK;3. Dipartimento di Chimica, Università degli Studi di Parma, Parco Area delle Scienze 17/A, Parma 43124, Italy;4. Dipartimento di Scienze del Farmaco, Sezione Chimica, Università di Catania, Viale Andrea Doria, 6, 95125 Catania, Italy;1. Institute of Chemical Sciences, Faculty of Science, P. J. ?afárik University, Moyzesova 11, 040 01 Ko?ice, Slovak Republic;2. Department of Pharmacology, Faculty of Medicine, P. J. ?afárik University, SNP 1, 040 66 Ko?ice, Slovak Republic;1. Merck & Co., Inc., MRL., Department of Medicinal Chemistry, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA;2. Merck & Co., Inc., MRL., Department of Structure Elucidation, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA;3. Merck & Co., Inc., MRL., Department of Viirology, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA |
| |
| Abstract: | An efficient synthetic approach for the preparation of enantiomerically pure carbocyclic d-4′-C-methylribonucleosides 3a–f is reported. The key intermediate, d-2,3-O-cyclohexylidene-4-methylcyclopentenone 8, was prepared starting from d-ribose in eight steps via an oxidative rearrangement. Conjugate addition of a catalytic vinylcopper(I) reagent to the α,β-unsaturated ketone 8 yielded cyclopentyl alcohol 10, which bears a quaternary stereogenic carbon at the C4-position. The cyclopentyl alcohol 10 was subsequently coupled with 6-chloropurine or 2-amino-6-chloropurine via an SN2 reaction, followed by a series of functional group transformations and deprotections to furnish purine ribonucleosides 3a–c. Pyrimidine bases were constructed on cyclopentylamine 29 using a linear approach, which furnished the pyrimidine nucleosides 3d–f. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
