D-Arbinose-Based Synthesis of homo-C-d4T and homo-C-thymidine

Abstract

2,3,5-Tri-O-benzyl-D-arabinofuranosyl halides (chloride, bromide) were reacted with AllMgBr, MeMgBr, and VinMgBr to furnish anomeric mixtures of the C-glycosyl products. The factors that influenced the beta/alpha ratio are discussed. The alpha,beta-C-vinyl derivative was transformed into 1-deoxy-1-C-hydroxymethyl-beta- and -alpha-D-arabinofuranoses (2,5-anhydro-D-glucitol and -mannitol, respectively), separable after isopropylidenation step. 2,5-Anhydro-1,3-O-isopropylidene-D-glucitol was converted into 2,5-anhydro-6-O-triphenylmethyl-D-erythro-hex-3,4-enitol and 2,5-anhydro-4,6-di-O-benzoyl-3-deoxy-D-ribo-hexitol, which were coupled with N-3-benzoylthymine under the Mitsunobu conditions to furnish two analogs of nucleosides with a -CH(2)- insert between sugar moieties and thymine.

Recent Advances in the Chemical Synthesis of C-Glycosides

“…Treatment of glucosaminyl α-chloride 26 with KCN under phase-transfer conditions gave β-cyanide 27 in 39% yield . Substitution of arabinosyl α-chloride 28 with allylmagnesium bromide afforded C -arabinoside 29 as a mixture of the anomers (∼73%, β/α = 4:1), whereas reaction of 2-deoxyribosyl α-chloride 30 with arylmagnesium bromide led to C -glycoside 31 (51%, β/α = 1:3) in favor of the α-anomer. − C -Glycosylation of 2-thio-( p -tolyl)-glucopyranosyl chloride 32 with 2-methylthiophene using Zn­(CN) 2 as a promoter might proceed through an episulfonium-like intermediate ( A ), providing β- C -glucoside 33 in 60% yield. − …”

Dimethyl hydrazine-1,2-dicarboxylate–triphenylphosphine oxide (1/1)

“…For the structures of analogous compounds, see: Anderson et al (1996); Hé roux & Brisse (1997); Wang et al (2007). For the synthesis of this and related compounds, see Doboszewski (1997Doboszewski ( , 2009.…”

“…Data collection: GIS (Bruker, 2010); cell refinement: APEX2 (Bruker, 2010) and SAINT (Bruker, 2009); data reduction: SAINT and XPREP (Bruker, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008b); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008b); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) and Mercury (Macrae et al, 2008); software used to prepare material for publication: PLATON (Spek, 2009).…”

2,6-Anhydro-1,3-di-O-benzyl-D-mannitol

“…For syntheses of this and similar compounds, see: Barker (1970); Doboszewski (1997Doboszewski ( , 2009; Doboszewski & de Siqueria (2010); Hartman (1970a,b). For related structures, see: Boeyens et al (1983); Doboszewski & Nazarenko (2003); Guiry et al (2008); Hong et al (2005); Vidra et al (1982).…”

“…1) is technically a β-C-glycoside of D-arabinofuranose. We prepared it in its protected form 4 starting from 2,3,5-tri-O-benzyl-D-arabinofuranosyl chloride or bromide (Doboszewski, 1997(Doboszewski, , 2009. The structure of 4 was confirmed by X-ray crystallography (Doboszewski & Nazarenko, 2003).…”