合成路线1

The synthetic precursor (XXIV) can be prepared by a number of alternative methods.
Condensation of 2,3-O-isopropylidene-D-glyceraldehyde (XVI) with ethyl 2-fluoropropionate (XXXI) by means of LDA in cold THF gives a mixture of diastereomeric fluoro-hydroxy esters (XXXIIa) and (XXXI-Ib) along with minor amounts of isomer (XXXIIc). After removal of the undesired (2S,3R)-isomer (XXXIIb) by selective enzymatic hydrolysis with Candida antarctica lipase form B (CALB), the remaining mixture of fluoro-hydroxy esters (XXXIIa) and (XXXIIc) undergoes cyclization to the respective lactones (XXIII) and (XXXIII) upon heating with aqueous H2SO4 (8). Esterification of the mixture of diols (XXIII) and (XXXIII) with benzoyl chloride and DMAP in Et3N/CH3CN followed by recrystallization of the resulting dibenzoates from isopropanol provides compound (XXIV) (8, 9). Scheme 4.
In a related method, chlorination of 2-fluoropropionic acid (XXXIV) with oxalyl chloride and catalytic DMF in toluene followed by reaction with pyrrolidine leads to amide (XXXV). Subsequent condensation of fluoro-amide (XXXV) with glyceraldehyde acetonide (XVI) by means of LDA in THF produces fluoro-hydroxyamide (XXXVIa), which upon heating with aqueous AcOH generates lactone (XXIII) along with minor amounts of its diastereoisomer (XXXIII). Similarly, condensation of S-phenyl 2-fluoropropanethioate (XXXVII) with aldehyde (XVI) yields hydroxy thioester (XXXVIb), which undergoes cyclization to lactones (XXIII) and (XXXIII) under acidic conditions (9). Scheme 4.
In a further related method, acyl benzoxazolone (XXXIX) —prepared by coupling 2-fluoropropionic acid (XXXIV) with benzoxazolone (XXXVIII) in the presence of DCC and DMAP— is condensed with glyceraldehyde acetonide (XVI) by means of TiCl4 and Et3N in CH2Cl2 to furnish adduct (XL). Subsequent hydrolysis and cyclization of (XL) in AcOH/H2O at 90 °C produces the mixture of lactones (XXIII) and (XXXIII) (9). Scheme 4.