Cyclopropyl and Related Analogs of the Anti-HIV Compound, Isodideoxyadenosine

Abstract

Novel 3'-substituted isonucleoside analogs were designed on the basis of the similarities of their electrostatic potential with the active anti-HIV compound, (S,S)-isodideoxy-adenosine. The key synthetic step involved coupling between the dideoxygenated sugar derivatives, 10 and 14, and adenine under Mitsunobu conditions. Anti-HIV data are mentioned.

Nucleosides with Transposed Base or 4′-Hydroxymethyl Moieties and Their Corresponding Oligonucleotides

“…Likewise, the 3′-α-methylisonucleoside 86 lacks activity against HIV-1, HSV, VZV, and CMV. 96 Interesting results were obtained with the ring-expanded oxetanocin analogues 87a−d. 97 The adenine congener 87a displays potent ganciclovir-like broad-spectrum antiviral activity against HCMV (EC 50 = 4.4 μM), HSV-1 and HSV-2 (EC 50 = 33.9 and 37.…”

“…The spironucleoside 92 lacks activity against HIV-1, HSV, VZV, and CMV. 96 The AZT mimic 93a 102,103 fails to show promising anti-HIV activity. The synthesis of diastereomers 94 is reported without biological evaluation.…”

Racemic Synthesis of Novel 6'-Methylene-5'-norcarbocyclic Purine Phosphonic Acid Analogues via Mitsunobu Reaction

“…The combined organic layer was washed with brine, dried over anhydrous MgSO 4 , filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/hexane, 1:15) to give 7 (1.34 g, 76%) as a colorless oil: (8). NaH (60% in mineral oil, 131 mg, 3.32 mmol) was added portion-wise to a cooled (0°C ) solution of secondary alcohol 7 (632 mg, 2.77 mmol) and p-methoxybenzyl chloride (0.41 mL, 3.04 mmol) in anhydrous DMF (10 mL).…”

“…8 Stimulated by these findings that 6'-electronegative nucleoside analogues and 5'-norcarbocyclic nucleoside phosphonates have excellent biological activities, we sought to synthesize a novel class of nucleosides comprising 6'-methylene-5'-norcarbocyclic phosphonic acid analogues in order to search for more effective therapeutics against HIV and to provide analogues for probing the conformational preferences of enzymes associated with the nucleoside kinases of nucleosides and nucleotides.…”

Synthesis of 4′/5′-Spirocyclopropanated Uridine and d-Xylouridine Derivatives and Their Activity against the Human Respiratory Syncytial Virus

“…Nevertheless, side effects of established therapeutics and the evolution of viral drug resistance have revealed a lack of appropriate new drug classes. During the past few decades the cyclopropyl motif has shown astonishing biological effects in drug development and was finally introduced as a spirocyclo­propanation motif of the d -ribose scaffold by Mulard et al − Since then, spirocyclo­propanations have been realized at carbons 2′, 3′, and 4′ by the addition of difluoromethylene ( I ) or methylene units, generated from metal reagents or diazomethane (Figure ). ,− Although 4′/5′-methylene spirocyclo­propanated uridine derivatives have been synthesized by the groups of Boyer and Robins, one aspect of the native substitution pattern of the nucleoside, namely the 5′-hydroxyl group at the spirocyclopropane, has been neglected. , In fact, conservation of the 5′-hydroxy motif for polycyclic ( II ) or spirocyclopropanated systems ( III ) proves challenging, as literature-known spirocyclopropanation protocols for nucleosides require electronically neutral, exocyclic, primary alkenes.…”