Synthesis of Methylene-Expanded 2‘,3‘-Dideoxyribonucleosides

Abstract

A method for the preparation of methylene-expanded 2‘,3‘-dideoxyribonucleosides is reported. The very inexpensive starting material levoglucosenone 8 was converted into the known mixture of alcohols 12ab which were converted into the required silyl ether alcohol 26 in six steps via either of two routes. The first involved a one-step acetylation and opening of the anhydro sugar bridge to give the triacetates 20ab which were reduced with triethylsilane and silyl triflate to afford the diacetates 21ab, both of which gave 26 after further functional group conversions. The second route entailed a simple acetylation of 12ab followed by reduction with triethylsilane and silyl triflate to give the monoacetates 19ab, both converted via straightforward chemistry into 26. Mesylation of the alcohol of 26 furnished the mesylate 27. Alkylation of adenine with the mesylate 27 afforded the silyl ether 28 which was deprotected to give the desired modified dideoxy nucleoside 7a. Alkylation of 2,6-diaminopurine 38 with the mesylate gave the protected diaminopurine nucleoside 39. Upon acetylation, it produced a mixture of di- and monoacetates 40 − 41, the latter of which was transformed into the desired guanosine analogue 7e. Thus, two new nucleoside analogues 7ae were prepared from levoglucosenone 8.

Oxidative and hydrolytic cleavage of cyclopropane and spirocyclobutane derivatives of 6,8-dioxabicyclo[3.2.1]octane, the products of transformation of levoglucosenone

“…For comparison, in the structures of 3,7,9 trioxatricyclo [4.2.1.0 2,4 ]nonanes containing a syn oxirane ring, the spin spin coupling constant 3 J 1,2 is about 4.6 Hz. 18 Treatment of (1S,2S,4R,5S,6R) spiro(7,9 dioxatricy clononane 5,2´ cyclobutanone) (16) with 1.5 fold molar excess of MCPBA leads to the spirojoined lactone 20 with high stereoselectivity (90% yield) (Scheme 6). The same lactone 20 can be also obtained in 72% yield by oxidation of cyclobutanone 16 with equimolar amount of KMnO 4 in acidic medium and in this case, the reaction comes to completion within several minutes.…”

“…The solvent was evaporated in vacuo and the residue was recrystallized from benzene to obtain colorless crystals (0.50 g, ∼90%) containing compounds 18 and 19 ( 1 H and 13 C NMR data) in the molar ratio ∼10 : 1. (1R,4S,5R) 2´ Oxospiro{6,8 dioxabicyclo[3.2.1]oct 2 ene 4,5´ oxolane} (18). 1 (16) (108 mg, 0.6 mmol) and MCPBA (155 mg, 0.9 mmol) in CH 2 Cl 2 (10 mL) was stirred for 10 h and then neutralized with saturated aq.…”

Reactions of levoglucosenone and its derivatives with diazo compounds

“…On heating in aqueous ethanolic solution of KOH and subsequent acidification to pH 2.5-3, esters 11a,b are converted to 2 {6,8 dioxabicyclo[3.2.1]oct 2 en 4 yloxy} acetic acid (14) in up to 95% yield. Acid 14 is not very stable in air and changes with time from a light orange oil to a dark viscous mass.…”

Ring‐Opening Metathesis Polymerization of Biomass‐Derived Levoglucosenol

“…However,f ossil resources are not infinite on earth and exploitation will have to come gradually to ah alt. [3] Levoglucosenone is ab ridged heterocyclic vinyl ketone,which is used as abuilding block in organic synthesis but is difficult to polymerize.H owever,t he simple reduction of the ketone functionality yields the alcohol levoglucosenol, [4] which we found to be as uitable monomer for ring-opening metathesis polymerization (ROMP) [5] using ad erivative of the 2 nd generation Grubbs catalyst. [1] Cellulose is one of the most abundant products of biomass and therefore an attractive renewable feedstock for the production of value-added chemicals such as sugars,l actic acid, levulinic acid, and furans.…”