合成路线1

The intermediate chiral phosphonamide (XXXII) has been obtained as follows: The treatment of arabitol (XIX) with the Moffat reagent (alpha-acetoxy-isobutyric acyl chloride) (XX) gives the intermediate (XXI), which, without isolation, by treatment with NaOMe and with Tbdms-Cl yields the silylated diepoxide (XXII). The condensation of (XXII) with ethoxyethynyl lithium (XXIII) by means of BF3/Et2O, HgCl2 and Ts-OH affords the bis(lactone) (XXIV), which is methylated by means of methyl iodide and LDA to provide the dimethyl analogue (XXV). The hydrolysis and desilylation of (XXV) by means of HF, followed by reprotection with benzyl trichloroacetimidate, and exhaustive methylation with NaH and methyl iodide gives the chiral nonanedioic dimethyl ester (XXVI). The reductive cleavage of the benzyl ether group with H2 over Pd(OH)2, followed by cyclization by means of PPTS yields the lactone (XXVII). The reduction of (XXVII) with L-selectride, followed by protection with propane-1,3-dithiol and BF3/Et2O affords the 1,3-dithiane (XXVIII). The reduction of the lactone group of (XXVIII) with LiAlH4, followed by reaction with PPh3 and I2 provides the chiral nonyl iodide (XXIX). The protection of the OH group of (XXIX) by means of Tbdms-OTf gives the silyl ether (XXX), which is finally condensed with lithium derived ethylphosphonamide (XXXI) to yield the intermediate chiral phosphonamide (XXXII).