合成路线1

The preparation of segment C (I) can be accomplished as follows. One-pot treatment of 4-chloro-3-nitrobenzoic acid (XXVIII) with Na2S and Ac2O/AcOH gives 2-methylbenzothiazole-5-carboxylic acid (XXIX), which is subsequently reduced with LiAlH4 in boiling THF followed by reoxidation of the obtained alcohol (XXX) with DMSO and SO3-pyridine complex to give the aldehyde (XXXI) (2). In an alternative procedure, aldehyde (XXXI) is produced by coupling of 5-chloro-2-methylbenzothiazole (XXXII) with acrylic acid in the presence of Pd2(dba)3 and NiBr2 followed by oxidative cleavage of the resulting arylacrylic acid (XXXIII) with OsO4 and NaIO4 (1). Aldol condensation of aldehyde (XXXI) with the chiral N-acetyloxazolidinone (XXXIV) by means of BuLi and ZnCl2 produces adduct (XXXV) as the major diastereoisomer. After protection of the free hydroxyl group of (XXXV) as the corresponding tert-butyldimethylsilyl ether (XXXVI), the chiral auxiliary group is removed by treatment with titanium ethoxide in boiling EtOH. The resulting ethyl ester (XXXVII) is then reduced to alcohol (XXXVIII) employing DIBAL in cold toluene/CH2Cl2. Subsequent reaction of alcohol (XXXVIII) with I2 and PPh3 provides the alkyl iodide (XXXIX), which is then displaced with triphenylphosphine in hot toluene, producing the target phosphonium salt (I) (1, 2). Scheme 4.