Levulinoyl deprotection

Cycle Used with Glycosyl Phosphate Activation and Levulinoyl Deprotection... 

After developing procedures for the activation and coupling of anomeric trichloroacetimidate and glycosyl phosphate donors as well as for the deprotection of acetyl and levulinoyl esters, we designed a synthesis utilizing all aspects of our automated chemistry. Trisaccharide 24, composed of three... 

Deprotection and sulfation was achieved by reduction of the azide to the corresponding acetamide with thioacetic acid [75] to afford III.47 (Scheme 29). Subsequent de-levulinoylation followed by acetylation gave III.48 in 64% yield over two steps. Reductive opening of the bisbenzylidene acetals with sodium cyanobo-rohydride and acid [76] afforded III.49 in 51% yield and by-product III.50, formed by acetyl migration from C3 to C4 (31%). Sulfation of III.49 was carried out with the sulfur trioxide-trimethylamine complex to give III.51 in 92% yield. Deacetylation followed by hydrogenolysis provided the target tetrasaccharide III.52. 

Kore, Yang and Srinivasan described the efficient synthesis of two 3 -dNTPs, namely 2 -deoxycytidine- and 2 -deo>g7adenosine-3 -0-triphos-phate (14, Scheme 5), which are regioisomers of dNTPs. Several compounds of this class were found to be potent inhibitors of adenylyl cyclases, while the reported methods of their synthesis were cumbersome and inefficient. Commercially available iV -Bz-5 -0-levulinoyl-2 -deoxyadenosine (15) or A/ -Bz-5 -0-levulinoyl-2 -deo3q cytidine (5 -0-DMT protected nucleosides were inappropriate for this reaction) were mono-phosphorylated (POC /trimethyl phosphate, room temperature) to form the phosphodichloridate intermediate 16 in 98% yield. Tributylamine was used as a scavenger of HCl. Then tributylammonium pyrophosphate, tributylamine, and acetonitrile were added to the reaction mixture, whereas final deprotection was done with concentrated aqueous ammonia at room temperature. Both 3 -dNTPs were obtained in ca. 50% overall yield. 

Deprotection of the levulinoyl group on trisaccharide 20 by use of hydrazine acetate [23] afforded 21 (85.4%) which was then used as an acceptor for the a-... 

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