Additive-controlled asymmetric iodocyclization enables enantioselective access to both α- and β-nucleosides

Wang, Qi; Mu, Jiayi; Zeng, Jie; Wan, Lin-Xi; Zhong, Yang-Yang; Li, Qiuhong; Li, Yitong; Wang, huijing; Chen, Fen‐Er

doi:10.1038/s41467-022-35610-w

Cited by 8 publications

(4 citation statements)

References 68 publications

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“…The development of methodology for the synthesis of nucleoside analogues and other heterocyclic N -glycosides is an active area of research . Problems of current interest include de novo assembly, site-selective modification, biocatalytic synthesis, and stereoselective preparation of P -chiral derivatives (e.g., aryloxy phosphoramidates (ProTides), phosphorothioates) . Formation of the bond between the heterocycle and carbohydrate by N -glycosylation is another important challenge to be addressed .…”

Section: Introductionmentioning

confidence: 99%

Boronic Acid-Catalyzed Regio- and Stereoselective N-Glycosylations of Purines and Other Azole Heterocycles: Access to Nucleoside Analogues

Desai,

Yatzoglou,

Turner

et al. 2024

J. Am. Chem. Soc.

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In the presence of an arylboronic acid catalyst, azole-type heterocycles, including purines, tetrazoles, triazoles, indazoles, and benzo-fused congeners, undergo regio-and stereoselective N-glycosylations with furanosyl and pyranosyl trichloroacetimidate donors. The protocol, which does not require stoichiometric activators, specialized leaving groups, or drying agents, provides access to nucleoside analogues and enables late-stage N-glycosylation of azole-containing pharmaceutical agents. A mechanism involving simultaneous activation of the glycosyl donor and acceptor by the organoboron catalyst has been proposed, supported by kinetic analysis and computational modeling.

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Section: Introductionmentioning

confidence: 99%

Boronic Acid-Catalyzed Regio- and Stereoselective N-Glycosylations of Purines and Other Azole Heterocycles: Access to Nucleoside Analogues

Desai,

Yatzoglou,

Turner

et al. 2024

J. Am. Chem. Soc.

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“…Further, iodo compounds were also converted into 195-199 respectively (Scheme 18). 59 Scheme 18 Reagents and Conditions: i) 194, NIS, NaI, 4 A MS, 0 o C, PhMe: CHCl3 = 1:1, DBU; ii) 195, NIS, PPh3S, 4 A MS, 0 o C, CH2Cl2, DBU; iii) NIS, Na2CO3, NaI; iv) NIS, Na2CO3, PPh3S; v.) DBU, CH2Cl2, 0 o C quant; vi) Bu3SnH, AIBN, PhMe, reflux, 85%; vii) NaBH4, THF: H2O = 3:1, 0 o C to rt, 94%; viii) Bu3SnH, AIBN, PhMe, reflux; ix) NaBH4, THF: H2O = 3:1, 0 o C to rt, 77% over two steps.…”

Section: Intramolecular Cyclization Reactionmentioning

confidence: 99%

Current Strategies on the Enantioselective Synthesis of Modified Nucleosides

Pal,

Chandra,

Mondal

et al. 2023

Synlett

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After the isolation of two carbocyclic nucleosides, viz Neplanocin A and Aristeromycin, from natural sources, a revolution came into the scientific community to develop more versatile, therapeutically useful compounds. For this purpose, many new methods for the synthesis of the carbocyclic framework of nucleosides have been developed. The consequences of this effort led to the successful development of many marketable drugs. Due to the inherent benefits such as higher lipophilicity and metabolic stability associated with carbocyclic nucleosides, like resistance against glycosidic hydrolysis and modification of aromatic bases by cellular phosphorylases, make them popular for the development of drugs against cancer and different viruses. Classically, carbocyclic nucleosides of various ring sizes and configurations have been synthesized starting from a chiral pool such as ribose and glucose, etc., but recently, many other new asymmetric versions have also been developed. Herein, we present a recent development in the catalytic enantioselective synthesis of nucleoside analogues, including carbocyclic and other varieties. This review provides new insights into the future development of modified nucleosides.

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“…Many of them, including those containing unnatural l -ribose and 2-deoxy- l -ribose (e.g., telbivudine in Figure ), require the crucial N -glycosylation to connect riboses/2-deoxyriboses with nucleobases (i.e., purines and pyrimidines) through glycosidic linkages in the natural β-orientation. However, N -glycosylation of nucleobases poses a formidable challenge in carbohydrate chemistry due to multiple factors such as the poor nucleophilicity of nucleobases and the N9/N7 regioselectivity issue of purines . In particular, feasible glycosylation conditions for 2-deoxyribosyl donors, which are highly reactive and susceptible to hydrolysis and elimination, are even more limited.…”

Section: Introductionmentioning

confidence: 99%

Direct Synthesis of α- and β-2′-Deoxynucleosides with Stereodirecting Phosphine Oxide via Remote Participation

Tang,

Zhou,

Wang

et al. 2024

J. Am. Chem. Soc.

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2′-Deoxynucleosides and analogues play a vital role in drug development, but their preparation remains a significant challenge. Previous studies have focused on β-2′-deoxynucleosides with the natural β-configuration. In fact, their isomeric α-2′-deoxynucleosides also exhibit diverse bioactivities and even better metabolic stability. Herein, we report that both αand β-2′-deoxynucleosides can be prepared with high yields and stereoselectivity using a remote directing diphenylphosphinoyl (DPP) group. It is particularly efficient to prepare α-2′-deoxynucleosides with an easily accessible 3,5-di-ODPP donor. Instead of acting as a H-bond acceptor on a 2-(diphenylphosphinoyl)acetyl (DPPA) group in our previous studies for syn-facial O-glycosylation, the phosphine oxide moiety here acts as a remote participating group to enable highly antifacial Nglycosylation. This proposed remote participation mechanism is supported by our first characterization of an important 1,5-briged P-heterobicyclic intermediate via variable-temperature NMR spectroscopy. Interestingly, antiproliferative assays led to a α-2′-deoxynucleoside with IC 50 values in the low micromole range against central nervous system tumor cell lines SH-SY5Y and LN229, whereas its β-anomer exhibited no inhibition at 100 μM. Furthermore, the DPP group significantly enhanced the antitumor activities by 10 times.

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Additive-controlled asymmetric iodocyclization enables enantioselective access to both α- and β-nucleosides

Cited by 8 publications

References 68 publications

Boronic Acid-Catalyzed Regio- and Stereoselective N-Glycosylations of Purines and Other Azole Heterocycles: Access to Nucleoside Analogues

Boronic Acid-Catalyzed Regio- and Stereoselective N-Glycosylations of Purines and Other Azole Heterocycles: Access to Nucleoside Analogues

Current Strategies on the Enantioselective Synthesis of Modified Nucleosides

Direct Synthesis of α- and β-2′-Deoxynucleosides with Stereodirecting Phosphine Oxide via Remote Participation

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