Development of New Efficient

Synthetic Methods for Docetaxel

 Synthesis of docetaxel
Docetaxel is a clinically well established anti-mitotic chemotherapy
medication used mainly for the treatment of breast,
ovarian, and non-small cell lung cancer
greatdifficulty exists in the total synthesis of docetaxel because of its
complex structure,Since 10-deacetyl baccatin III (10-DAB
III) was extracted in large scale from the renewable and readily
available European yew tree Taxus baccata,4 however, the effective
semi-synthesis of docetaxel was started to reduce synthetic
difficulty and cost of docetaxel dramatically.
 protect both C-3’ NH2and C-2’ OH groups of (2R, 3S)-phenylisoserine
(1) with 1,1-dichloroacetone

CH3COCHCl2

2R,3S)-3-Phenylisoserine

then ,hydrolyzed with 3N LiOH and treated with 3N HCl to provide

the corresponding carboxylic acids

Et3N,LiOH, MeOH,
With respect to 10-DAB both hydroxyl groups of C-7
and C-10 were protected with tribromoacetyl chloride
Coupling of acid with 7,10-diprotected baccatin III
was carried out by using DCCN,N'-Dicyclohexylcarbodiimide
and catalytic amount of4-Dimethylaminopyridine
DMAP as coupling reagents

DCC, DMAP,
toluene/DMF,

A range of alcohols can be esterified using a carboxylic acid in

the presence of DCC and a catalytic amount of DMAP.
The carboxylic acid reacts with DCC to a O-acyl isourea, which is more reactive than the free acid

The alcohol attacks this intermediate, forming DCU and the corresponding ester

dicyclohexylurea
 Treatment with c-HCl, followed by the introduction of tBoc Di-tert-
butyl dicarbonate intoC-3’ NH2 of phenylisoserine side chain

HCl, (tBoc)2O

Finally, the removal of tribromoacetyl group with ammonium acetate

AcONH4, MeOH/THF