A significant proportion of current chemotherapeutic treatments for cancer involve the use of anti-metabolites, particularly modified nucleoside analogues that possess a capability to mimic native purine or pyrimidine nucleosides, which can disrupt metabolic and regulatory pathways. Notwithstanding this significant medicinal capability, therapeutic intervention using nucleoside analogues is often limited by poor cellular uptake, low conversion to the active triphosphate metabolite, rapid degradation or clearance and development of resistance profiles in certain cell types. Consequently, research activity in this field continues to develop syntheses for next generations of nucleoside analogues that can overcome these limitations and provide new therapeutic options. Within this context, 4'-thionucleosides, where the furanose ring oxygen is substituted with sulfur, have received attention from several academic and industrial groups since a first disclosure of 4'-thioadenosine in the early 1960's; Figure highlights some key achievements in this area. Bioisosteric replacement of furanose oxygen with larger sulfur seeks to explore the biological effect, imparted through changes to furanose ring conformation and the hydrolytic stability of a thiohemiaminal glycosidic linkage. Insertion of a sulfur atom to access thiofuranose components generally start from available chiral pool materials and the use of thiourea to convert 4,5-epoxides to 4,5-thiiranes, 8,9 alongside sodium sulfide-mediated formation of 2,5-bicyclic systems are notable examples of key intermediates developed to enable this. Open chain systems have also been used, for example, effecting double displacement of a 1,4-bismesylate with Na2S to access 1-deoxy thiofuranoses, and both C1 aldehyde and thioacetal oxidation levels have delivered access to anomeric thioglycosides. Two main approaches have been adopted to install appropriate nucleobases; firstly thioglycosylation of a OH silylated nucleobase, and, secondly a Pummerer-type reaction of the sulfoxide to condense with a corresponding nucleobase. Hypervalent iodine reagents have also been used to effect a similar transformation. As part of a program exploring chemical synthesis approaches to next generation nucleoside scaffolds, we were interested in accessing appropriate 4'-thionucleosides and templating this bioisosteric replacement onto established chemotypes, a tactic recently implemented by Liotta and colleagues for 2ʹ-C-methyl-4ʹ-thionucleosides. Herein we report our synthesis of 4'-thio and 4'sulfinyl nucleosides; we targeted an open-chain C1-oxime to enable sulfur inclusion using displacement of an appropriate 4-position leaving group, with concomitant ring closure onto a C1 aldehyde. This was intended to provide a benchmark in then accessing related 2'-deoxy-2',2'-gemdifluoro and D-arabino structures which, alongside recent examples 2'-deoxy-2'-fluoro and L-3ʹ-deoxy-3ʹ,3ʹ-difluoro systems, provides capability to more broadly study 4'-thionucleoside chemotypes and their structure activity relationships. These aims are highlighted in Figure .