Base Moiety Research Articles

A New Biodegradable Linear mPEG‐b‐poly(Schiff Base‐Acetal) Copolymer Carrier Co‐Delivery Cinnamaldehyde and Gemcitabine for Combined Anticancer Therapy

AbstractDue to significant pH difference among the healthy tissue, tumor tissue as well as intracellular endo/lysosome, constructing pH‐responsive biodegradable nanodrug delivery systems has received more and more attention. Herein, double‐end alkenylated acetal monomer (based on cinnamaldehyde (CA)) and double‐end sulfhydrylation Schiff base monomer were designed and synthesized, and three pH‐responsive biodegradable block copolymer mPEG‐b‐poly(Schiff base‐acetal) (P1), mPEG‐b‐poly(acetal) (P2), and mPEG‐b‐poly(Schiff base) (P3) were obtained by Michael addition reaction. All these polymers could be self‐assembled with gemcitabine (GEM) to form GEM‐loaded micelles. Proton nuclear magnetic resonance (1H NMR) and dynamic light scattering (DLS) experiments proved that these polymer micelles have good pH responsiveness. The size and morphology of both blank and GEM‐loaded micelles were characterized by DLS and scanning electron microscope (SEM). The GEM/P1, GEM/P2, and GEM/P3 micelles exhibited pH‐sensitive drug release properties and the GEM/P1 micelles has the relatively fastest drug release rate. Containing multiple acetal and Schiff base moieties GEM/P1 micelles showed fastest cellular internalized rate and best in vitro antitumor activity among all GEM‐loaded micelles.

Construction novel polybenzoxazine coatings exhibiting corrosion protection of mild steel at different concentrations in a seawater solution

In this work, a new and effective polymeric coating is used to improve mild steel's corrosion resistance. The coating incorporates a Schiff base moiety into a benzoxazine (BZ) precursor, resulting in improved protection against corrosion. The SF-Tol-BZ polymerization behavior and thermal properties were studied using differential scanning calorimetry (DSC) and thermalgravimetric analysis (TGA), respectively, at different curing temperatures. The poly(SF-Tol-BZ) cured at 240 °C had a Td10 value of 604 °C and a Tg of 225 °C. The efficacy of poly(SF-Tol-BZ) coatings in protecting mild steel (MS) from corrosion in a NaCl (3.5%) solution at room temperature was evaluated using various corrosion measurements, including open circuit potential (OCP), and electrochemical impedance spectroscopy (EIS). The results showed that increasing the poly(SF-Tol-BZ) concentration led to a corresponding increase in its protective efficiency, reaching a maximum of 92% at a concentration of 300 g/L. The coatings also exhibited a 24-fold increase in Rct values and a one-order-of-magnitude reduction in CPE compared to the bare mild steel. Finally, the poly(SF-Tol-BZ) precursors demonstrated a CO2 uptake of 23 mg g−1 (measured at 298 K).

Structure-Function Analysis of the S-Glycosylation Reaction in the Biosynthesis of Lincosamide Antibiotics.

The S-glycosyltransferase LmbT, involved in the biosynthesis of lincomycin A, is the only known enzyme that catalyzes the enzymatic incorporation of rare amino acid L-ergothioneine (EGT) into secondary metabolites. Here, we show the structure and function analyses of LmbT. Our in vitro analysis of LmbT revealed that the enzyme shows promiscuous substrate specificity toward nitrogenous base moieties in the generation of unnatural nucleotide diphosphate (NDP)-D-α-D-lincosamides. Furthermore, the X-ray crystal structures of LmbT in its apo form and in complex with substrates indicated that the large conformational changes of the active site occur upon binding of the substrates, and that EGT is strictly recognized by salt-bridge and cation-π interactions with Arg260 and Trp101, respectively. The structure of LmbT in complex with its substrates, the docking model with the EGT-S-conjugated lincosamide, and the structure-based site-directed mutagenesis analysis revealed the structural details of the LmbT-catalyzed SN 2-like S-glycosylation reaction with EGT.

Structure‐Function Analysis of the S‐Glycosylation Reaction in the Biosynthesis of Lincosamide Antibiotics

AbstractThe S‐glycosyltransferase LmbT, involved in the biosynthesis of lincomycin A, is the only known enzyme that catalyzes the enzymatic incorporation of rare amino acid L‐ergothioneine (EGT) into secondary metabolites. Here, we show the structure and function analyses of LmbT. Our in vitro analysis of LmbT revealed that the enzyme shows promiscuous substrate specificity toward nitrogenous base moieties in the generation of unnatural nucleotide diphosphate (NDP)‐D‐α‐D‐lincosamides. Furthermore, the X‐ray crystal structures of LmbT in its apo form and in complex with substrates indicated that the large conformational changes of the active site occur upon binding of the substrates, and that EGT is strictly recognized by salt‐bridge and cation‐π interactions with Arg260 and Trp101, respectively. The structure of LmbT in complex with its substrates, the docking model with the EGT‐S‐conjugated lincosamide, and the structure‐based site‐directed mutagenesis analysis revealed the structural details of the LmbT‐catalyzed SN2‐like S‐glycosylation reaction with EGT.

Multifunctional fluorogenic probes from hydrazide schiff base-modified polyvinylpyrrolidone to detect Al3+ in aqueous environment and living cells

Recent efforts have been made to develop chemosensors for aluminum cation (Al3+) detection to monitor the concentration of an aluminum metal ion in both the environment and biological systems due to the high health risks associated with aluminum exposure. Hence the development of chemosensory with multifunctionality has advantages over traditional approaches. Therefore, multi-functional chemosensor materials were fabricated with colorimetric, chromogenic, and fluorogenic probes from the hydrazone-based polyvinylpyrrolidone (PVP-NDHIP) were designed by Atom Transfer Radical Addition Polymerization (ATRP) approach. The Schiff base moiety was conjugated with different chain lengths of PVP to provide good aqueous solubility, low detection limits, enhanced selectivity, and sensitivity of the probes. As a result, the PVP-NDHIP probes showed substantial fluorescence enhancement in linearity upon adding Al3+ ions with a low detection limit of a few nanomolar by fluorescence detection in an aqueous solution. Especially, PVP-NDHIP with Mw of 10,000 g/mol (PVP-NDHIP10k) presented the most sensitive absorption and fluorescence titrations performance with 26.4 nM and 3.9 nM, respectively. Furthermore, the PVP-NDHIP probes demonstrated excellent performance in water and various aqueous cosolvent environments, such as DIW/DMSO, DIW/THF, DIW/DMF, DIW/Ethanol, and DIW/Methanol. Moreover, the obtained probe was used for internalization and Al3+ intracellular imaging. The findings explained that hydrazone-based polyvinylpyrrolidone could create a critical role as a multifunctional approach in both environmental contamination and Al3+ related pathway in a biological system.

Synthesis of a magnetic nanomaterial with core–shell structure for effective Au(III) recovery from solution with superior separation and one-step reduction

To synthesize a novel magnetic nanomaterial for effective Au(III) recovery from the aqueous phase with excellent capability, superior selectivity, one-step reduction and ease of separation after loading Au(III) still remains a huge challenge. In this study, a magnetic nanomaterial (γ-Fe2O3@PDA-NAM) with a core–shell structure was synthesized for effective Au(III) recovery by sorption. The maximum Au(III) sorption capacity by γ-Fe2O3@PDA-NAM reached 2910 mg/g at pH = 6.10 ± 0.15, 44.29 times that by γ-Fe2O3 (65.7 mg/g). Its Au(III) sorption efficiency was over 97.75% at very low concentrations (i.e., 5.5 × 10-4 and 5.5 × 10-5 mg/mL). TEM, XPS and FTIR analysis verified that excellent Au(III) recovery by γ-Fe2O3@PDA-NAM resulted from N/S-containing soft base moieties introduced to different layers. N and/or S elements at these sites provided lone pair electrons to Au(III) to form stable coordination bond. Meanwhile, the hydrogen bond between O-containing (–OH, -C=O) and N-containing (-C-N, -N(-C)-N-, -C=N) moieties on γ-Fe2O3@PDA-NAM and –OH on the main speciations of Au(III) (AuCl3(OH)-, AuCl2(OH)2-, and AuCl(OH)3-) also greatly enhanced Au(III) recovery. About 78.03% of Au(III) was directly reduced to elemental gold by -C-S- and -N(-C)-N- group on the tertiary amine structure during sorption. More than 98.84% of Au(III) was selectively sorbed on γ-Fe2O3@PDA-NAM at pH 4.0 even though Pt(IV), Cu(II), Zn(II), Pb(II), and Ni(II) were co-present at the same concentration as that for Au(III) (0.01 mg/mL). In contrast, sorption efficiency of other interfering ions was within 1.75–26.05%. A relatively poor sorption selectivity for Pt(IV) could be acceptable because it is also a noble metal.

Desing, synthesis, and characterization of some 5,6‐dichloro benzimidazole derivatives with investigation of their antioxidant and elastase inhibitory activities

AbstractStarting from the 5,6‐dichloro‐2‐phenyl‐1H‐benzimidazole, new benzimidazole derivatives having schiff base, carbothioamide, thiadiazole, and triazole moiety were synthesized and characterized. Synthesized compounds were characterized by NMR spectroscopy, mass spectroscopy and elemental analyses techniques. Antioxidant and elastase inhibitory activities of compounds were also investigated. The inhibitory effects on elastase activity of the synthesized molecules were analyzed spectrophotometrically. The antioxidant activities of molecules were investigated by both methods as DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) free radical scavenging activity and iron reducing power capacities. All synthesized compounds showed good antioxidant and elastase inhibitory activity. Compound 2 showed the highest elastase inhibition. Compound 3 and compound 2 showed the highest antioxidant activity by DPPH method, and iron reducing power method, respectively.

Molecular determinants of inhibition of UCP1-mediated respiratory uncoupling

Brown adipose tissue expresses uncoupling protein 1 (UCP1), which dissipates energy as heat, making it a target for treating metabolic disorders. Here, we investigate how purine nucleotides inhibit respiration uncoupling by UCP1. Our molecular simulations predict that GDP and GTP bind UCP1 in the common substrate binding site in an upright orientation, where the base moiety interacts with conserved residues R92 and E191. We identify a triplet of uncharged residues, F88/I187/W281, forming hydrophobic contacts with nucleotides. In yeast spheroplast respiration assays, both I187A and W281A mutants increase the fatty acid-induced uncoupling activity of UCP1 and partially suppress the inhibition of UCP1 activity by nucleotides. The F88A/I187A/W281A triple mutant is overactivated by fatty acids even at high concentrations of purine nucleotides. In simulations, E191 and W281 interact with purine but not pyrimidine bases. These results provide a molecular understanding of the selective inhibition of UCP1 by purine nucleotides.

Theoretical Calculations of Organic Salts and Their Correlation with Proton Conductivity

In the field of high-temperature polymer electrolyte membrane fuel cells, the concern over the proton conductor possible to apply to the high-temperature anhydrous condition has risen. Thus, poly(4-vinylpyridine)s were employed as not only an organic donor polymer with pyridine rings as the base but also heat-resistant materials. We introduced various acids as the acceptors into the polymer side chain through the acid–base reaction to form poly(4-vinylpyridinium salt)s (PVPySAs). The verification that the substituent design as the model in the polymer side chain of PVPySAs by the density functional theory was carried out to discuss what influences their high or low proton conductions. The results indicated that the shortened protonated atomic distance between acid and base moieties enhanced the conductivity of the organic salts. In addition, the pKa and number of protons of the used acid groups give an effect on the proton conductivity.

Experimental and Theoretical Exploration of ESIPT in a Systematically Constructed Series of Benzimidazole Based Schiff Base Probes: Application as Chemosensors.

Herein, we have utilized 2-(2-hydroxyphenyl)benzimidazole (HBI) to synthesize 3-(1H-benzoimidazol-2-yl)-2-hydroxy-5-methyl-benzaldehyde (HBIA) followed by three Schiff bases by using -ortho (H2 BIo), -meta (H3 BIdm) and -para (H2 BIp) substituted amino benzoic acids and studied their photophysical properties. We have successfully derived molecular structures of HBI, HBIA and H3 BIdm which reveals that in HBI and HBIA, the phenolic -OH is intramolecularly hydrogen bonded with sp2 N of benzimidazole group whereas in H3 BIdm, it is hydrogen bonded with imine C=N of Schiff base moiety, which is responsible for different solid state emission properties of the reported compounds. Extensive experimental and theoretical studies show that for all three Schiff bases, in solution due to activation of C=N isomerization, ESIPT operates through benzimidazole site and displays different emission from the solid state. Furthermore, H2 BIo, H3 BIdm and H2 BIp selectively sense Cu2+ in semi aqueous medium with nano-molar detection limit and in HuH-7 cells through the inhibition of ESIPT of process.

SiRNA: A Comprehensive Review of Marketed Products till August 2022

Small interference RNA (siRNA) is a double-stranded RNA of 21~25 nucleotides. siRNA functions using a natural phenomenon known as RNA interference (RNAi), a gene silencing mechanism. Hypothetically, siRNA can target and regulate the expression of any disease-related gene in a sequence-specific manner. In 1993, this mechanism was noticed in a nematode Caenorhabditis elegans, later discovered in humans. After two decades, in 2018, the first siRNA therapeutics (Patisiran) were developed successfully and got approval from USFDA. Followed by three more siRNA drugs (Givosiran, Lumasiran, and Inclisiran) approved in consecutive years to treat rare, inherited genetic disorders. Recently approved one is Vutisiran with a similar indication of patisiran. Limitation of conventional therapies, this new & standard pharmacotherapy opens a new era of changing the treatment options of human diseases. Six siRNA candidates are in phase III clinical trials and are hoped to enter the pharmaceutical market soon. Challenges faced during the development of these novel therapies were off-target effects, target-specific delivery, cellular uptake, recognition by the innate immune system, limited efficacy, and others. However, chemical modification of the siRNA nucleotides in sugar, base, and phosphate moiety makes it successful in overcoming obstacles. In addition, a non-viral delivery carrier also helped in many aspects during formulation. This study is a narrative review and will summarize pharmacokinetic, pharmacodynamic, design approaches, and other attributes faced during the development of marketed siRNA products.

Optically active polyaromatic Schiff base adopting stable secondary structures

The polycondensation of N-((3,5-diamino)benzoyl)-ʟ-alanine dodecyl ester (1L) with p-phthalaldehyde (2) was carried out to obtain poly(1L-2), a novel optically active polymer containing Schiff base moieties in the main chain. A series of analogous polymers with Schiff base moieties were also synthesized from N-((3,5-diamino)benzoyl)-ᴅ-alanine dodecyl ester (1D) and N-((3,5-diamino)benzoyl)glycine dodecyl ester (1G) with various feed ratios. The polymers exhibited CD signals assignable to exciton coupling-based chirality in CHCl3 depending on the feed molar ratios of 1L/1D and 1L/1G. Poly(1L-2) exhibited lyotropic liquid crystallinity in CHCl3 and THF.

A novel cobalt(ii) acetate complex bearing lutidine ligand: a promising electrocatalyst for oxygen evolution reaction.

Developing cost-effective electrocatalysts using earth-abundant metal as an alternative to expensive precious metal catalyst remains a key challenge for researchers. Several strategies are being researched/tested for making low-cost transition metal complexes with controlled electron-density and coordination flexibility around the metal center to enhance their catalytic activity. Herein, we report a novel lutidine coordinated cobalt(ii) acetate complex [(3,5-lutidine)2Co(OAc)2(H2O)2] (1) as a promising electrocatalyst for oxygen evolution reaction (OER). Complex 1 was characterized by FT-IR, elemental analysis, and single crystal X-ray diffraction data. The structure optimization of complex 1 was also done using DFT calculation and the obtained geometrical parameters were found to be in good agreement with the parameters obtained from the solid state structure obtained through single crystal X-ray diffraction data. Further, the molecular electrostatic potential (MEP) maps analysis of complex 1 observed electron rich centers that were found to be in agreement with the solid-state structure. It was understood that the coordination of lutidine as a Lewis base and acetate moiety as a flexible ligand will provide more coordination flexibility around the metal center to facilitate the catalytic reaction. Further, the electron rich centers around metal center will also support the enhancement of their catalytic activity. Complex 1 shows impressive OER activity, even better than the state-of-the-art IrO2 catalyst, in terms of turnover frequency (TOF: 0.05) and onset potential (1.50 V vs. RHE). The TOF for complex 1 is two and half times higher, while the onset potential is ca. 20 mV lower, than the benchmark IrO2 catalyst studied under identical conditions.

Synthesis of a novel fibrous material for effective Au(III) recovery with superior selectivity and one-step reduction

To synthesize a material for effective Au(III) recovery with excellent selectivity and one-step reduction from solution remains a huge challenge. In this study, a novel fibrous material was synthesized by treating carbon nanofibers with ammonia-plasma followed by N-Aminorhodanine assembly; it was used for Au(III) recovery by sorption. The results demonstrated that the maximum sorption capacity of Au(III) by the N-Aminorhodanine assembled-carbon nanofibers (N-AMCNFs) reached 229 mg/g, which is 20.6 times that by carbon nanofibers (11 mg/g). Excellent Au(III) recovery by N-AMCNFs mainly resulted from its extremely hydrophilic nature indicated by a contact angle of 2.69 ° and the newly-introduced N- and S-containing soft base moieties (-C-N, -CN, -C-S and -CS). These sites provided electrons for coordination chelation with soft acid Au(III). Electrostatic attraction between AuCl4- and the positively-charged N-AMCNFs also served as a driving force for Au(III) recovery. Importantly, 44.3% of Au(III) was reduced to Au(0) by electrons transferred from S- and N-sites on rhodanine during sorption, as proved by XRD and XPS analysis. Besides, N-AMCNFs exhibited superior recovery selectivity indicated by above 96.24% recovery efficiency for Au(III) at pH 4 in the presence of multiple interfering ions including Cu(II), Ni(II), Zn(II), and Pb(II) at 50 mg/L as Au(III), but their recovery was below 2%.

Synthesis of Novel Bis-imino and Bis-amino Curcuminoids for Evaluation of Their Anticancer and Antibacterial Activity.

A new set of curcumin analogues with a Schiff base moiety were synthesized from a bis-aldehyde derivative of hydroxybenzylidene cyclohexanone and various alicyclic and aromatic amines. The single crystals of compound 2 (bis-aldehyde), compound 3b (bis-cyclohexylimino derivative), and compound 3c (bis-1-imino piperidyl derivative) were developed. The said bis-imino and bis-amino curcuminoids were tested for anticancer activity against MCF-7 utilizing the conventional MTT assay. These Schiff bases had significantly higher anticancer efficacy than curcumin and methotrexate against MCF-7 cell lines. Compounds 3k, 3b, and 3l have the highest efficacy among all synthesized curcuminoids. The MTT results are in accordance with the binding affinities found by docking the said molecules with HER2 Tyrosine Kinase (HER2-TK). Compound 3b is identified as a promising HER2-TK inhibitor and also shows effective inhibition against Gram-positive bacteria Staphylococcus aureus.

Assessing the Formation of Purine Lesions in Mitochondrial DNA of Cockayne Syndrome Cells.

Mitochondrial (mt) DNA and nuclear (n) DNA have known structures and roles in cells; however, they are rarely compared under specific conditions such as oxidative or degenerative environments that can create damage to the DNA base moieties. Six purine lesions were ascertained in the mtDNA of wild type (wt) CSA (CS3BE-wtCSA) and wtCSB (CS1AN-wtCSB) cells and defective counterparts CS3BE and CS1AN in comparison with the corresponding total (t) DNA (t = n + mt). In particular, the four 5',8-cyclopurine (cPu) and the two 8-oxo-purine (8-oxo-Pu) lesions were accurately quantified by LC-MS/MS analysis using isotopomeric internal standards after an enzymatic digestion procedure. The 8-oxo-Pu levels were found to be in the range of 25-50 lesions/107 nucleotides in both the mtDNA and tDNA. The four cPu were undetectable in the mtDNA both in defective cells and in the wt counterparts (CSA and CSB), contrary to their detection in tDNA, indicating a nonappearance of hydroxyl radical (HO•) reactivity within the mtDNA. In order to assess the HO• reactivity towards purine nucleobases in the two genetic materials, we performed γ-radiolysis experiments coupled with the 8-oxo-Pu and cPu quantifications on isolated mtDNA and tDNA from wtCSB cells. In the latter experiments, all six purine lesions were detected in both of the DNA, showing a higher resistance to HO• attack in the case of mtDNA compared with tDNA, likely due to their different DNA helical topology influencing the relative abundance of the lesions.

The Urinary Bladder is Rich in Glycosphingolipids Composed of Phytoceramides

Glycosphingolipids (GSLs) are composed of a polar glycan chain and a hydrophobic tail known as ceramide. Together with variation in the glycan chain, ceramides exhibit tissue-specific structural variation in the long-chain base (LCB) and N-acyl chain moieties in terms of carbon chain length, degree of desaturation, and hydroxylation. Here, we report the structural variation in GSLs in the urinary bladders of mice and humans. Using TLC, we showed that the major GSLs are hexosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, Neu5Ac-Gal-Glc-Ceramide, and Neu5Ac-Neu5Ac-Gal-Glc-Ceramide. Our LC-MS analysis indicated that phytoceramide structures with a 20-carbon LCB (4-hydroxyeicosasphinganine) and 2-hydroxy fatty acids are abundant in hexosylceramide and Neu5Ac-Gal-Glc-Ceramide in mice and humans. In addition, quantitative PCR demonstrated that DES2 and FA2H, which are responsible for the generation of 4-hydroxysphinganine and 2-hydroxy fatty acid, respectively, and SPTLC3 and SPTSSB, which are responsible for the generation of 20-carbon LCBs, showed significant expressions in the epithelial layer than in the subepithelial layer. Immunohistochemically, dihydroceramide:sphinganine C4-hydroxylase (DES2) was expressed exclusively in urothelial cells of the urinary bladder. Our findings suggest that these ceramide structures have an impact on membrane properties of the stretching and shrinking in transitional urothelial cells.

Synthesis and Characterization of Schiff Base Polymers via Metal Coordination and Its Application in Infrared Stealth Coating.

In order to reduce the infrared emissivity to meet the requirements of modern warfare for infrared stealth materials, we prepared the polymers containing Schiff base moieties using polyetheramine and 2,6-pyridinedicarboxaldehyde by solution polycondensation and coordinated with Ni2+, Cu2+, and Sm3+ ions to prepare organic coatings. The structure and the thermal and mechanical properties of the coatings were studied in detail. Meanwhile, the effect of the conductivity change of coordination polymers on infrared emissivity was studied systematically. The results showed the polymer coordinated with Sm3+ ions had the lowest energy band gap, which was 2.99 eV, and the best electrical conductivity of 3.54 × 10-4 S/cm compared with Ni2+ and Cu2+ coordination polymers. The infrared emissivity was the lowest in the 2-22 μm infrared waveband range, which reached 0.58, suggesting the polymers containing Schiff base moieties and their coordination polymers may have a great potential to be applied as infrared stealth materials in military applications.

The interactive effect between the oxazole-containing optical switch nucleus and carbazole-containing salicylidene Schiff base: Enhancing photoreactivity and tuning the ion sensing property

A functionalized diarylethene derivative consisting of an oxazole-containing optical switch nucleus and an appending carbazole-containing Schiff base unit was synthesized. The interactive effect of optical switch nucleus and carbazole-containing Schiff base was studied. Introducing a suitable receptor into diarylethene nucleus not only provided a useful strategy for controlling the photoreactivity, but also constructed an effective approach to tuning the ion sensing property. Specifically, appending a carbazole-containing Schiff base moiety to the oxazole-containing optical switch nucleus, the molar absorption coefficient, and the cyclization quantum yield was obviously enhanced. Adding the oxazole-containing optical switch nucleus to the carbazole-containing Schiff base, discrimination of Fe3+ and Cu2+ without any auxiliary reagent was achieved. This study provides a novel design strategy not only for modulating the photoreactivity, but also for the development of optical sensor for discrimination of Fe3+ and Cu2+ ions.

DAST-Mediated Fluorination of 1-[4-Thio-β-d-arabinofuranosyl]uracil: Investigation of Thiolane vs Thietane Formation and Stereoselective Synthesis of 4′-ThioFAC

AbstractThe unprecedented DAST-mediated (DAST = diethylaminosulfur trifluoride) deoxygenative fluorination of benzoyl-, TBDPS-, and Bn-protected 1-(β-d-4-thioarabinofuranosyl)uracil at the sugar portion was examined. Three kinds of nucleoside (Ns) products were formed: target thiolane Ns, ring-contracted thietane Ns, and anhydro Ns products. The reaction pathway was determined by the electronic effect of the protecting groups at the sugar and base moieties. The benzoylated uracil starting material gave the 2,2′-anhydronucleoside (anhydro Ns) as a major product, whereas the silylated and benzylated starting materials furnished the corresponding fluorinated products, in which the ring-contracted thietanes predominantly formed. The desired thiolane Ns could be obtained as major product by the addition of a pyridine derivative as an additive. Upon reacting N 3-benzoylated 1-(β-d-4-thioarabinofuranosyl)uracil with DAST in the presence of 2,4,6-collidine, the target 2′-deoxy-2′-β-fluoro-4′-thiouracil nucleoside could be obtained in 72% isolated yield along with the corresponding thietane Ns (7%) and anhydro Ns (3%) (thiolane Ns/thietane Ns/anhydro Ns = 10.3:1.00:0.43), with recovery of the starting material (12%). In this study, the first stereoselective synthesis of the β-anomer of 1-(2-deoxy-2-fluoro-4-thio-β-d-arabino-pentofuranosyl)cytosine (4′-thioFAC) has been developed.