Abstract
The one-pot azidation and benzoylation of a mixture of cis (-)-menthyl phenylglycidates provide quantitatively the corresponding (2R,3S)-, and (2S,3R)-3-azido-1-((1R,2S,5R)-2-isopropyl-5methylcyclohexyloxy)-1-oxo-3-phenylpropan-2-yl benzoate. Enantiopure (2R,3S)-3-azido-1((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy)-1-oxo-3-phenylpropan-2-yl benzoate crystallize from MeOH at room temperature in high yields. The reduction of the latter with Zn-TMSCl produces (-)-menthyl 3-benzamido-3-phenyl-2-(trimethylsilyloxy)propanoate which upon simultanious desilylation and hydrolysis provide the taxol side chain N-benzoyl-(2R,3S)-3phenylisoserine.
Highlights
The natural product Taxol,[1] isolated from Taxus brevifolia, is considered the most promising anticancer drug.[2]
Our retrosynthetic plan for the synthesis of taxol side chain is depicted in Scheme 1
Taxol side chain 5 can be prepared from the hydrolysis of menthyl ester 4 which in turn could be prepared by the reduction of azide 3
Summary
The natural product Taxol,[1] isolated from Taxus brevifolia, is considered the most promising anticancer drug.[2] Because of the limited content in the bark of Taxus brevifolia, and the uneconomical production by total synthesis,[3] extensive efforts have been focused on semisynthesis[4] of taxol by the condensation of commercially available 10-deacetylbaccatin III with a side chain such as N-benzoyl-(2R,3S)-3-phenylisoserine (-)-5 (Figure 1). The efficient synthesis of enantiopure side chain has attracted much attention from academic community as well as industry.[5]. Enriched phenylglycidates, are the most frequently used precursors of the taxol C-13 phenylisoserine side chain and diltiazem.5a,e,f,i Asymmetric epoxidation and asymmetric dihydroxylation are the main methods used in the preparation of optically active cis and trans phenylglycidates.[6] An alternative way to prepare enantiopure epoxides is the asymmetric applications of the Darzen’s reaction.[7]. We report on the use of (2R,3R)- and (2S,3S)-(-)-menthyl 3-phenyloxirane-2-carboxylates8 2-2’ (Scheme 2) in the asymmetric syntheses of (2R,3S)- (-)-5 and (2S,3R)-3-benzoylamino-2hydroxy-3-phenylpropionic acid (+)-5 (Scheme 2)
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