A practical synthesis of (2R)-3,5-di-O-benzoyl-2-fluoro-2-C-methyl-d-ribono-γ-lactone

A General and Enantioselective Approach to Pentoses: A Rapid Synthesis of PSI-6130, the Nucleoside Core of Sofosbuvir

“…Importantly, such a strategy would employ catalysis-derived starting materials in place of chiral pool precursors (e.g., isopropylidene-protected glyceraldehydes), 8 which have been shown to be poorly or nonselective in similar de novo nucleoside syntheses. 9 Moreover, our building blocks would be easily modified to provide a variety of differentially substituted products and would allow for preinstallation of protecting groups, thereby obviating the need for extraneous protection–deprotection sequences. Herein we describe the successful execution of these design ideals and outline a generic and enantioselective route to nucleoside architecture.…”

Biocatalytic routes to anti-viral agents and their synthetic intermediates

“…79 En route to sofosbuvir's nucleoside moiety, Cleary and co-workers employed highly versatile Candida antarctica lipase B (CAL-B) to resolve a mixture of aldol products. By doing so, enantiomerically pure intermediate 28 80 was obtained in the desired configuration by starting from 33 g of aldol product (Scheme 8). 81 This intermediate was initially synthesised in enantiomerically enriched form through lithium diisopropylamide (LDA)-catalysed aldol addition of ethyl 2-fluoropropanoate (27) to (R)-glyceraldehyde acetonide (26).…”

“…Sofosbuvir's sugar fragment has been prepared through a lithium diisopropylamide (LDA)-promoted aldol addition of ethyl 2-fluoropropanoate (27) to (R)-glyceraldehyde acetonide (26). 80 However, this reaction resulted in a mixture of stereoisomers that required additional resolution and down-stream purification in order to isolate (2R,3R)-28 in pure form (Scheme 69A). This type of transformation would thus likely profit from the use of a biocatalyst as these often provide excellent stereoselectivity.…”

Candida antarctica Lipase B as Catalyst for Cyclic Esters Synthesis, Their Polymerization and Degradation of Aliphatic Polyesters

“…Another way, to obtain γ-lactone (a building block in the synthesis of anti-HCV agent) was proposed by Zhang et al [34]. In their experiment, 2,3-O-isopropylidene-d-glyceraldehyde condensed with ethyl 2-fluoropropionate getting a mixture of three isomeric products.…”