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An asymmetric transfer hydrogenation via dynamic kinetic resolution of a broad range of rac- α-(purin-9-yl)cyclopentones was first developed. A series of cis-β-(purin-9-yl)cyclopentanols were obtained with up to 97% yield, >20/1 dr, and >99% ee. This also provides an efficient synthetic route to a variety of chiral carbocyclic nucleosides.

An efficient method to construct chiral acyclic nucleosides via Sharpless asymmetric dihydroxylation of N-allylpyrimidines or N-alkenylpurines is reported. A range of chiral acyclic nucleosides with two adjacent hydroxyl groups present on the side chains could be produced in good yields (up to 97% yield) and excellent enantioselectivities (90-99% ee). The synthetic utility of the reaction was demonstrated by the catalytic asymmetric synthesis of ( S)-Cidofovir and ( R)-Buciclovir.

With 9-(2-tosylvinyl)-9H-purines as the dipolarophiles, a series of chiral azacyclic nucleosides with four continuous stereocenters were obtained in 86-99% yields, >20:1 dr, and 94 → 99% ee via the Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition. Both (E)- and (Z)-9-(2-tosylvinyl)-9H-purines were suitable dipolarophiles, enriching the structure diversity of azacyclic nucleosides. Furthermore, when α-methyl imino ester was explored, the corresponding azacyclic nucleoside with a chiral quaternary stereocenter could also be afforded with excellent results.

A straightforward entry to chiral carbocyclic nucleoside analogues has been realized via the enantioselective [3+2] cycloaddition of α-nucleobase substituted acrylates to vinyl cyclopropanes for the first time. With Pd2(dba)3-L5 as the catalyst, carbocyclic purine, uracil, and thymine nucleoside analogues with quaternary stereocenters were obtained in excellent yields (up to 99% yield) and good enantioselectivities (up to 92% ee).

The diversity-oriented synthesis of acyclic nucleosides has been achieved via ring-opening of vinyl cyclopropanes with purines. With Pd2(dba)3·CHCl3 as a catalyst, the 1,5-ring-opening reaction proceeded well and afforded N9 adducts as the major form, in which the C=C bonds in the side chain were exclusively E-form. In the presence of AlCl3, the 1,3-ring-opening reaction occurred smoothly, giving N9 adducts as the dominate products. Meanwhile, when MgI2 was used as the catalyst, the 1,3-ring-opening reaction also worked well to form N7 adducts.

A rapid and divergent access to chiral azacyclic nucleoside analogues has been established via highly exo-selective and enantioselective 1,3-dipolar cycloaddition of azomethine ylides with β-nucleobase substituted acrylates. Using 1 mol% of a chiral copper complex, various chiral azacyclic nucleoside analogues were obtained in high yields, excellent exo-selectivities and enantioselectivities (98 to >99% ee).

A new strategy to construct acyclic nucleosides with diverse side chains was developed. With Ag(I) salts as catalysts, the hydrocarboxylation, hydroamination, and hydrocarbonation reactions proceeded well, affording acyclic nucleosides in good yields (41 examples, 60-98% yields). Meanwhile, these reactions exhibited high chemoselectivities and E-selectivities.

A novel and efficient synthetic method has been developed for the preparation of chiral acyclic nucleosides with a chiral amino side chain by Mitsunobu reaction between nucleoside bases and protected L-serine. This method suggests a potentially more efficient and complementary process to acquire chiral acyclic nucleosides.

The enantioselective synthesis of carbocyclic nucleosides through the palladium‐catalyzed asymmetric allylic amination of alicyclic Morita‐Baylis‐Hillman (MBH) adducts with purines was successfully developed. With a combination of Pd2(dba)3/L7 as catalyst, various optically active carbocyclic nucleosides featuring a C=C double bond in the carbocycle moiety were obtained in high yields (up to 97%) with excellent N9/N7‐selectivities (>95/5) and enantioselectivities (up to >99.6%). In addition, these nucleoside analogs allowed for rapid transformation to a variety of other interesting structurally diverse chiral carbocyclic nucleosides. [ABSTRACT FROM AUTHOR]

An efficient route to acyclic purine nucleoside analogues with an amino group at the C1′ position of the side chains has been reported. Using Sc(OTf)3 as the catalyst, the ring‐opening reaction of purines with aminocyclopropanes afforded acyclic nucleoside analogues with moderate to good yields and in a regioselective manner. Furthermore, phenyl cyclopropane also gave the desired acyclic nucleoside analogue with a phenyl linked at C1′ position. Furthermore, generation of a penciclovir analogue may also occur from the ring‐opening product via a reduction reaction. [ABSTRACT FROM AUTHOR]

Abstract: N‐Heteroaromatic substituted acrylates are employed in the phosphine‐catalyzed [3+2] annulation with allenes for the first time, affording regiospecific carbocyclic nucleoside analogues in an α‐addition manner. Various chiral carbocyclic nucleoside analogues containing a quaternary stereocenter and a C=C double bond are generated in good yields (up to 90% yield) and excellent enantioselectivities (up to 97% ee). α‐Purine‐containing disubstituted acrylate and α‐benzimidazole substituted acrylate are also suitable substrates for this reaction. [ABSTRACT FROM AUTHOR]

Abstract: A direct route to chiral pyrimidine acyclic nucleoside analogues with a sulfur‐containing side chain is reported via enantioselective tandem conjugated addition‐protonation reactions of thioacetic acid to α‐pyrimidine substituted acrylates. In the presence of a quinine‐derived thiourea catalyst, diverse chiral sulfur‐containing pyrimidine acyclic nucleoside analogues could be obtained in excellent yields (95–99 %) and with moderate to excellent enantioselectivity values (up to 99 % ee). [ABSTRACT FROM AUTHOR]

The synthesis of chiral cyclopropyl carbocyclic purine nucleoside analogues via the highly enantioselective intramolecular cyclopropanation reactions has been reported. With a chiral ruthenium(II)-phenyloxazoline complex as the catalyst, cyclopropyl carbocyclic purine nucleoside analogues containing three contiguous stereocenters were obtained with up to 99% yield and 99% ee. Furthermore, a chiral cyclopropyl carbocyclic adenosine nucleoside having anti-BLV activity could be synthesized in a concise manner using this strategy. [ABSTRACT FROM AUTHOR]

A new and efficient approach for the synthesis of acyclic nucleoside analogues with different side chains has been established for the first time via the insertion of carbenoids into N−H bond of nucleobases. With Sc(OTf)3 as the catalyst, various purine bases and α-diazoesters worked well, and gave the corresponding acyclic nucleosides in moderate-to-good yields (21 examples, up to 87 % yield) with good N9-regioselectivities (up to >99:1). Moreover, other N-heterocycles including pyrimidines, benzoimidazole, imidazole, carbazole, and pyrazole are also suitable substrates and afford the desired N−H insertion products with moderate-to-good yields. In addition, the enantioselective and chiral auxiliary induction N−H insertion reactions were also studied. [ABSTRACT FROM AUTHOR]

Push-pull-type purine nucleoside-based fluorescent sensor L1 bearing a chelating N, N-bis(2-pyridylmethyl)amine group at the C6 position was designed and synthesized. Sensor L1 showed clear and selective detection of Pd2+ in aqueous buffer, and it is the first 'on-off'-type purine nucleoside-based fluorescent sensor for Pd2+. [ABSTRACT FROM AUTHOR]

An efficient method for the synthesis of C6-functionalized purine nucleosides was developed viathe direct nucleophilic substitution reaction of 6-chloropurine derivatives with various mild nucleophiles. The eco-friendly solvent-free process gave good to high isolated yields within a short reaction time (5 min) under microwave irradiated conditions. [ABSTRACT FROM AUTHOR]

A novel one-step method for preparing C-5-substituted O6,5′-cyclopyrimidine nucleoside analogues is reported. This method employs molecular iodine to mediate the cyclization from the 5′-O-hydroxyl group of the sugar ring and C-6 at the position of the nitrogen base in ammonia water under mild conditions without any other aprotic organic solvent. [ABSTRACT FROM AUTHOR]

Novel C6-phosphonated purine nucleosides were obtained in good to excellent isolated yields by the simple and catalyst-free SNAr-Arbuzov reaction of trialkyl phosphite with 6-choloropurine nucleosides, including a series of nonsugar carbon nucleosides. Shorter reaction times were needed, and substantially higher yields were obtained under microwave irradiation conditions compared with conventional heating conditions. [ABSTRACT FROM AUTHOR]

Syntheses of acyclic nucleosides were achieved in water with the aid of microwave irradiation, providing a rapid, efficient and convenient method for the preparation of acyclic nucleosides in high yields. [ABSTRACT FROM AUTHOR]

A highly regioselective Pd-catalyzed CAr–H bond activation method was developed for the modification of purines (nucleosides) with different functional groups by using purine as a directing group. This approach provides a new access to a variety of functionalized purines (nucleosides) which are potentially of great importance in medicinal chemistry. [ABSTRACT FROM AUTHOR]

Novel 6-[N,N-bis(2-hydroxyethyl)amino]purine nucleosides were prepared in one step by nucleophilic substitution reaction of 6-choloropurine nucleosides with diethanolamine. Shorter reaction times and higher yields were achieved under microwave irradiation conditions in neat water. [ABSTRACT FROM AUTHOR]

Acyclic nucleosides and their phosphonates possess significantly antiviral and cytostatic activities. For acyclic nucleosides and their phosphonates, the introduction of a chiral group to their side chain or the absolute configuration of the chiral atom could affect their biological activities obviously. Thus, the asymmetric synthesis of chiral acyclic nucleosides and their phosphonates has received continuous attention. The previous reports mainly focus on employing the chiral pool and chiral auxiliary methods for the synthesis of chiral acyclic nucleosides and their phosphonates. In contrast, the asymmetric catalysis methods for the synthesis of acyclic nucleosides and their phosphonates are still in the beginning. This digest paper will serve to highlight the significant progress that has been made in these areas. [ABSTRACT FROM AUTHOR]

An efficient route to construct chiral acyclic purine nucleosides containing a hemiaminal ester moiety is reported via three-component dynamic kinetic resolution of purines, aldehydes, and acid anhydrides. The procedure provides diverse chiral acyclic purine nucleoside analogues in a regioselective manner with good yields (up to 93% yield) and excellent enantioselectivities (up to 95% ee). Furthermore, the chiral (acyloxyalkyl)-5-fluorouracil could also be generated as a potential prodrug of 5-fluorouracil. [ABSTRACT FROM AUTHOR]

An efficient route to chiral carbocyclic nucleoside analogues containing a quaternary stereocenter and a C-C double bond has been established via a highly enantioselective [3 + 2] annulation of Morita-Baylis-Hillman (MBH) carbonates with a-purine-substituted acrylates. With 20 mol % (S)-SITCP as the catalyst, various chiral carbocyclic nucleoside analogues with a quaternary stereocenter and a C-C double bond were obtained in high yields (up to 92%) with good diastereoselectivities (up to 10:1 dr) and excellent enantioselectivities (up to 96% ee). Furthermore, the corresponding products were subjected to diverse transformations to afford interesting and potentially useful chiral carbocyclic nucleosides. [ABSTRACT FROM AUTHOR]

A direct route to branched N-allylpyrimidine analogues is herein reported via the highly regio- and enantioselective asymmetric allylation of pyrimidines with racemic allylic carbonates. With [Rh(COD)Cl]2/chiral diphosphine as the catalyst, a range of chiral pyrimidine acyclic nucleosides could be obtained under neutral conditions in good yields (up to 95% yield) with high levels of regio- and enantioselectivities (15:1 to >40:1 B/L and up to 99% ee). Furthermore, chiral pyrimidine acyclic nucleoside bearing two adjacent chiral centers has been successfully synthesized by asymmetric dihydroxylation. [ABSTRACT FROM AUTHOR]

Review: [23 refs. [ABSTRACT FROM AUTHOR]

Utilizing Ag(I) salts as catalysts, hydrocarboxylation, hydroamination, and hydrocarbonation reactions proceed well affording acyclic nucleosides with good results. [ABSTRACT FROM AUTHOR]

Purine-fused tricyclic derivatives have been synthesized via a copper-catalyzed domino Michael/oxidative cross-coupling reaction between adenines and nitroolefins for the first time. With air as the oxidant, this method has high regioselectivity, which provides a new route for constructing purine-nucleoside-conjugated systems with two newly formed C-N bonds. Meanwhile, purine nucleosides with an exocyclic amino group could be obtained easily by simple reduction, which may lead to potential applications in fluorescence recognition of various bases in vivo. [ABSTRACT FROM AUTHOR]

A highlyregioselective Minisci reaction with the decarboxylativealkylation of purine nucleosides under mild conditions was developed.With 5 mol % AgNO3as a catalyst and (NH4)2S2O8as an oxidant, a series of purinenucleosides including ribosyl, deoxyribosyl, arabinosyl purine nucleosidesworked well with primary, secondary, and tertiary aliphatic carboxylicacids. [ABSTRACT FROM AUTHOR]

Purine is utilized as a new directing group for the Pd-catalyzed monoarylation of 6-arylpurines with simple aryl iodides via C−H bond activation in good yields, providing a complementary tool for the modification of 6-arylpurines (nucleosides). Most importantly, purine can be used as a building block for nucleoside derivatives, and the use of purine as a directing group helps avoid additional synthetic steps. [ABSTRACT FROM AUTHOR]

A novel and efficient synthetic method has been developed for the preparation of chiral acyclic nucleosides with a chiral amino side chain by Mitsunobu reaction between nucleoside bases and protected l-serine. This method suggests a potentially more efficient and complementary process to acquire chiral acyclic nucleosides. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis and fluorescence properties of novel purine analogues linked azacrown ether at C6 position were investigated. These new purine analogues could be prepared from a series of 6-chloropurines and showed selective and efficient signaling behaviors toward micromolar concentration of Ag+ ion over other common metal ions in an aqueous environment. [Copyright &y& Elsevier]

A facile and efficient method for direct synthesis of 6-methylpurines was developed through SNAr-based addition reactions between various 6-halopurine derivatives and ethyl acetoacetate with assistance of microwave irradiation, which underwent direct coupling reaction, in situ deacetylation and decarboxylation to yield 6-methylated purines in high to excellent yields within 10 min. [ABSTRACT FROM AUTHOR]

An abstract of the article "A Straightforward Entry to Chiral Carbocyclic Nucleoside Analogues via the Enantioselective [3 + 2] Cycloaddition of α-Nucleobase Substituted Acrylates" by Ming-Sheng Xie, Yong Wang, and Cong Du is presented.

A highly regioselective Minisci reaction for the decarboxylative alkylation of Purine derivatives under mild conditions is presented. [ABSTRACT FROM AUTHOR]