Hong-Ying Niu

Pd(II)-catalyzed ortho arylation of 6-arylpurines with aryl iodides via purine-directed C-H activation: a new strategy for modification of 6-arylpurine derivatives.

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.

Copper-Catalyzed Synthesis of Purine-Fused Polycyclics

A novel protocol for a Cu-catalyzed direct C((sp(2)))-H activation/intramolecular amination reaction of 6-anilinopurine nucleosides has been developed. This approach provides a new access to a variety of multiheterocyclic compounds from purine compounds via Cu-catalyzed intramolecular N-H bond tautomerism which are endowed with fluorescence.

Radical Route for the Alkylation of Purine Nucleosides at C6 via Minisci Reaction

A highly regioselective Minisci reaction with the decarboxylative alkylation of purine nucleosides under mild conditions was developed. With 5 mol % AgNO3 as a catalyst and (NH4)2S2O8 as an oxidant, a series of purine nucleosides including ribosyl, deoxyribosyl, arabinosyl purine nucleosides worked well with primary, secondary, and tertiary aliphatic carboxylic acids.

Highly Enantioselective Synthesis of Designed Chiral Acyclonucleosides and Acyclonucleotides by Organocatalytic Aza‐Michael Addition

Acyclonucleoside and acyclonucleotide analogues are currently used as antiviral drugs with a broad spectrum of activities. The discovery of acyclovir as an antiherpes agent stimulated the search for new antiviral nucleosides with an acyclic carbohydrate-mimicking chain. Some nucleosides and nucleotides with chiral carbons in the acyclic side chain, such as (S)-HPMPC (Cidofovir), (S)-HPMPA, (R)PMPA (Tenofovir), and (S)-DHPA, have been shown to possess various medicinal activities (Scheme 1). It is noteworthy that the absolute configuration of these compounds has a significant influence on their biological potency. For example, S enantiomers of DHPA and HPMPA exhibit antiviral activities, whereas the R enantiomers are markedly less active. Hence, there is considerable interest in the development of effective methods for the synthesis of optically active acyclonucleoside and acyclonucleotide analogues because of their significance in medicinal and nucleic acid research. There are two routes that are mainly employed for the synthesis of chiral acyclonucleoside and acyclonucleotide analogues. One route is based on the introduction of a chiral side chain to purine or pyrimidine bases, which involves alkylation and aza-Michael addition reactions of modified bases with the desired functionalized chiral side chains, or the ring-opening reaction of propylene oxide with a chiral carbon center. Unfortunately, the functionalized chiral side chains usually need to be prepared by lengthy or difficult processes, which thus limits these methodologies to particular types of substrates. The second route is based on the generation of chiral acyclonucleoside products selectively from achiral starting materials. Though this route opens an exceedingly valuable protocol for the synthesis of new, versatile chiral acyclonucleosides, only two examples of such asymmetric catalytic processes are known in the literature up to now. First, Jacobsen and Gandelman have shown that [(salen)Al] complexes can catalyze the conjugate addition of purine bases to a,b-unsaturated enones or imides, and that the products can be further reduced to chiral acyclonucleoside analogues. Second, Hartwig and Stanley have described how the N-allylation of purine bases catalyzed by metallacyclic iridium complexes gives the desired product, which can be converted to chiral acyclonucleoside analogues by reduction or dihydroxylation. These two methods both give chiral acyclonucleosides in high enantioselectivities, but their applications are restricted by the use of highly toxic and expensive organometallic complexes that are difficult to prepare, and by the multiple conversion steps to give the nucleosides. In addition, neither of the two examples gives acyclonucleotide analogues. These limitations prompted us to develop a method for the synthesis of optically pure acyclonucleoside and acyclonucleotide analogues from achiral starting materials. Organocatalysis has expanded widely over the last few years. To date, however, there has been no report on the organocatalytic synthesis of chiral acyclonucleoside and acyclonucleotide analogues. During our studies on the synthesis of purine analogues and taking into consideration reports [a] Prof. Dr. H.-M. Guo, Dr. T.-F. Yuan, J.-Y. Liu, R.-Z. Mao, D.-Y. Li, Prof. G.-R. Qu College of Chemistry and Environmental Science Key Laboratory of Green Chemical Media and Reactions of Ministry of Education, Henan Normal University 46 Jianshe Road, Xinxiang, 453007 (P. R. China) Fax: (+86) 373-332-9276 E-mail : guohm518@hotmail.com quguir@sina.com [b] Dr. H.-Y. Niu School of Chemistry and Chemical Engineering Henan Institute of Science and Technology 1 Hualan Avenue, Xinxiang 453003 (P. R. China) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201100435. Scheme 1. Structures of some acyclonucleosides and acyclonucleotides possessing antiviral activities.

Straightforward and highly efficient catalyst-free one-step synthesis of 2-(purin-6-yl)acetoacetic acid ethyl esters, (purin-6-yl)acetates, and 6-methylpurines through S(N)Ar-based reactions of 6-halopurines with ethyl acetoacetate.

A novel approach to the synthesis of purines bearing functionalized carbon substituents or methyl in position 6 was developed. Under different reaction conditions, 6-halopurine derivatives could react with ethyl acetoacetate efficiently to yield 2-(purin-6-yl)acetoacetic acid ethyl esters, (purin-6-yl)acetates and 6-methylpurines respectively. No metal catalyst and ligand were required.

Synthesis of acyclic nucleosides with a chiral amino side chain by the Mitsunobu coupling reaction.

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.

Direct Synthesis of 6-Arylpurines by Reaction of 6-Chloropurines with Activated Aromatics

Highly functionalized C6-aryl-substituted purine analogues were synthesized through direct arylation of 6-chloropurine with aromatics promoted by anhydrous AlCl(3) in a single step. The reactions, which were conducted using a 3-fold excess of AlCl(3) in refluxing 1,2-dichloroethane, gave moderate to excellent product yields in 0.5 h. This work is complementary to the classical coupling reactions for the synthesis of C6-aryl-substituted purine analogues.

The synthesis of novel fluorescent purine analogues modified by azacrown ether at C6.

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.

One-Pot Synthesis of 7,9-Dialkylpurin-8-one Analogues: Broad Substrate Scope

The one-pot and direct synthesis of 7,9-dialkylpurin-8-one analogues with broad substrate scope has been developed. This copper-catalyzed C-H oxidation reaction could avoid multistep synthesis of quaternary ammonium salts and expand the scope of halogenated alkanes. Moreover, benzimidazole derivatives are also applicable in the catalytic system.

Copper-Catalyzed Intramolecular Cyclization of N-Propargyl-Adenine: Synthesis of Purine-Fused Tricyclics

A novel protocol to construct fluorescent purine-fused tricyclic products via intramolecular cyclization of N-propargyl-adenine has been developed. With CuBr as the catalyst, a series of purine-fused tricyclic products were obtained in good to excellent yields (19 examples, 75-89% yields). When R2 was a hydrogen atom in N-propargyl-adenines, the reactions only afforded the endocyclic double bond products. When R2 was an aryl group, the electron-donating groups favored the endocyclic double bond products, while the electron-withdrawing groups favored the exocyclic double bond products.