合成路线1

The esterification of optical active (-)-N-methylephedrine (LXV) with octanoyl chloride (LXVI) in tert-butyl methyl ether gives the corresponding ester (LXVII), which is treated with trimethylsilyl chloride and butyllithium-diisopropylamine in THF to yield the enolic trimethylsilyl ether (LXVIII). The condensation of (LXVIII) with the previously obtained aldehyde, 3(R)-(benzyloxy)tetradecanal (XI) (scheme 11082301a), by means of TiCl4 in dichloromethane affords, after chromatography, (2S,3S,5R)-5-(benzyloxy)-2-hexyl-3-hydroxyhexadecanoic acid 2(S)-(dimethylamino)-1(R)-phenylpropyl ester (LXIX), which is finally hydrolyzed with methanolic KOH to (2S,3S,5R)-5-(benzyloxy)-2-hexyl-3-hydroxy-hexadecanoic acid (XIX), obtained in scheme 11082301a. The previously obtained 3(R)-(benzyloxy)tetradecanal (XI) can also be obtained by benzylation of 3(R)-hydroxytetradecanoic acid methyl ester (LXX) as usual, to the protected (LXXI), which is then reduced with DIBAL as before. Tetrahydrolipstatin can also be obtained from natural lipstatin by hydrogenation with H2 over Pd/C in ethanol.