Synthesis of 2′,3′‐Modified Carbocyclic <scp>L</scp>‐Nucleoside Analogues

Jessel, Sönke; Meier, Chris

doi:10.1002/ejoc.201001473

Cited by 14 publications

(5 citation statements)

References 54 publications

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“…The inversion of the hydroxyl in 98 under Mitsunobu conditions gave 99, which was treated with N 3 -benzoylthymine under Mitsunobu conditions to produce the carbocyclic nucleoside 100 and, finally, L-carba-d4T (101) after the removal of protecting groups. 41 Nucleosides 102 and 103 were also prepared in a straightforward manner from 100. The acetyl derivative of compound 98 is a suitable synthon to introduce bases by palladium catalysis.…”

Section: Derivatisation Of Cyclopentadiene Other Than Cycloadditionmentioning

confidence: 99%

Advances in the enantioselective synthesis of carbocyclic nucleosides

et al. 2013

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Carbocyclic nucleosides are nucleoside analogues in which the furanosidic moiety has been replaced by a carbocycle. Several members of this family have been isolated from natural sources and include a 5-membered ring carbocycle. The aim of this review is to examine critically the different methodologies for the enantioselective construction of 3- to 6-membered rings, with a particular focus on 5-membered rings and their modifications. The procedures for bonding the heterocyclic moiety and the carbohydrate are treated separately. The methods for synthesising the carbocyclic moiety mainly focus on the construction of the cycle, although precise details about the functionalisation are provided in some cases. The selected methods aim to provide an overview of the synthesis of carbocycles related to the synthesis of carbocyclic nucleosides. The methods of synthesis of 5-membered rings are classified into two types: methods in which the cyclopentane ring is formed by ring closing reactions (C=C and C-C formation) and methods that start from preformed 5-membered rings, based mainly on cycloaddition reactions. With respect to the methods of synthesis of 3-, 4- and 6-membered ring carbocyclic nucleosides, a selection of the more relevant enantioselective procedures is presented in a systematic manner.

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Section: Derivatisation Of Cyclopentadiene Other Than Cycloadditionmentioning

confidence: 99%

Advances in the enantioselective synthesis of carbocyclic nucleosides

et al. 2013

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“…Ultimately, we attempted to develop a route that would allow enantioselective synthesis of all three subseries 1 , 3 , and 4 . The utility of known chiral precursors proved to be limited: monoacetate 34 was not optimal due to the presence of difficult to remove acetonide, while the synthesis of compound 35 (especially the alkylation of cyclopentadienide) was in our hands extremely irreproducible. Similarly, attempted desymmetrization of diol 7b by enantioselective silylation or by pivaloylation with chiral variant of DMAP also failed.…”

Section: Resultsmentioning

confidence: 93%

Diastereoselective Flexible Synthesis of Carbocyclic C-Nucleosides

et al. 2017

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Carbocyclic C-nucleosides are quite rare. Our route enables flexible preparation of three classes of these nucleoside analogs from common precursors-properly substituted cyclopentanones, which can be prepared racemic (in six steps) or optically pure (in ten steps) from inexpensive norbornadiene. The methodology allows flexible manipulation of individual positions around the cyclopentane ring, namely highly diastereoselective installation of carbo- and heterocyclic substituents at position 1', orthogonal functionalization of position 5', and efficient inversion of stereochemistry at position 2'. Newly prepared carbocyclic C-analog of tubercidine, profiled in MCF7 (breast cancer) and HFF1 (human foreskin fibroblasts) cell cultures, is less potent than tubercidine itself, but more selectively toxic toward the tumorigenic cells.

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“…Above, we listed some of the L -nucleoside analogues with a solid demonstration of their therapeutic activities, which are summarized in Table 1 . Besides, there are many other nucleoside-like small molecules designed and evaluated as antiviral therapeutics, which had an L -configuration similar to its modified nucleoside, including cyclobutene L -nucleoside analogues [ 72 ], L -erythro-hexopyranosyl nucleosides [ 73 , 74 ], L -4′-C-ethynyl-2′-deoxypurine nucleosides [ 75 ], L -ribo-configured Locked Nucleic Acid [ 76 , 77 , 78 , 79 ], pyrrolo, pyrazolo, or imidazo-modified L -nucleoside [ 80 ], et al There have also been many methods developed to efficiently synthesize carbocyclic L -nucleoside analogues [ 52 , 81 , 82 , 83 ], and they have been summarized elsewhere [ 84 , 85 ].…”

Section: Nucleoside Analogs As Therapeutic Antiviral and Antitumor Agentsmentioning

confidence: 99%

Advances in Therapeutic L-Nucleosides and L-Nucleic Acids with Unusual Handedness

Dantsu

Zhang

2021

Genes

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Nucleic-acid-based small molecule and oligonucleotide therapies are attractive topics due to their potential for effective target of disease-related modules and specific control of disease gene expression. As the non-naturally occurring biomolecules, modified DNA/RNA nucleoside and oligonucleotide analogues composed of L-(deoxy)riboses, have been designed and applied as innovative therapeutics with superior plasma stability, weakened cytotoxicity, and inexistent immunogenicity. Although all the chiral centers in the backbone are mirror converted from the natural D-nucleic acids, L-nucleic acids are equipped with the same nucleobases (A, G, C and U or T), which are critical to maintain the programmability and form adaptable tertiary structures for target binding. The types of L-nucleic acid drugs are increasingly varied, from chemically modified nucleoside analogues that interact with pathogenic polymerases to nanoparticles containing hundreds of repeating L-nucleotides that circulate durably in vivo. This article mainly reviews three different aspects of L-nucleic acid therapies, including pharmacological L-nucleosides, Spiegelmers as specific target-binding aptamers, and L-nanostructures as effective drug-delivery devices.

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Synthesis of 2′,3′‐Modified Carbocyclic L‐Nucleoside Analogues

Cited by 14 publications

References 54 publications

Advances in the enantioselective synthesis of carbocyclic nucleosides

Advances in the enantioselective synthesis of carbocyclic nucleosides

Diastereoselective Flexible Synthesis of Carbocyclic C-Nucleosides

Advances in Therapeutic L-Nucleosides and L-Nucleic Acids with Unusual Handedness

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