Taxol side-chain

H2O2, NaHC03, THF. The 10-acetate, which is an a-keto acetate, is cleaved in the presence of the taxol side chain that is prone to hydrolysis with other reagents. ... 

The asymmetric epoxidation of electron-poor cinnamate ester derivatives was highlighted by Jacobsen in the synthesis of the Taxol side-chain. Asymmetric epoxidation of ethyl cinnamate provided the desired epoxide in 96% ee and in 56% yield. Epoxide ring opening with ammonia followed by saponification and protection provided the Taxol side-chain 46 (Scheme 1.4.12). 

Choudary, B.M., Chowdari, N.S., Mahdi, S., Kantam, M.L. (2003) A Trifimctional Catalyst for One-Pot Synthesis of Chiral Diols via Heck Coupling-N-Oxidation-Asymmetric Dihydroxyla-tion Application for the Synthesis of Diltiazem and Taxol Side Chain. Journal of Organic Chemistry, 6S, 1736-1746. 

Ill. Denis, J.N., Greene, A.E., Serra, A.A., Luche, M.J. (1986) An Efficient, Enantioselective Synthesis of the Taxol Side Chain. Journal of Organic Chemistry, 51, 46-50. 

Commer9on, A., Bezard, D., Bernard, F., Bourzat, J.D. (1992) Improved Protection and Esterification of a Precursor of the Taxotere and Taxol Side Chains. Tetrahedron Letters, 33, 5185-5188. 

Scheme 12.10 gives some examples of these oxidations. Entry 1 is one of several aryl-conjugated alkenes that were successfully epoxidized. Entry 2 is a reaction that was applied to enantioselective synthesis of the taxol side chain. Entry 3 demonstrates... 

Figure 7.15 Synthesis of the antipodes of A-benzoyl phenylisoserine Taxol side chain...

Feske, B.D., Kaluzna, I.A. and Stewart, J.D. (2005) Enantiodivergent, biocatalytic routes to both taxol side chain antipodes. The Journal of Organic Chemistry, 70 (23), 9654-9657. 

Jacobsen applied the salen-Mn(III) complex (J ,J )-121 in the synthesis of two antihypertensive agents 122 and 12386a (Scheme 4-41) and also the taxol side chain 124.8 6b... 

The structures of taxol and its polycyclic part baccatin III are shown in Figure 7-2, and the numbering of these two compounds is extensively used throughout the rest of this chapter. Because connecting the side chain to baccatin HI is just routine chemistry, we introduce only the synthesis of baccatin III and the taxol side chain. 

Several methods have been developed for the synthesis of the taxol side chain. We present here the asymmetric construction of this molecule via asymmetric epoxidation and asymmetric ring-opening reactions, asymmetric dihydroxylation and asymmetric aminohydroxylation reaction, asymmetric aldol reactions, as well as asymmetric Mannich reactions. 

Via Asymmetric Epoxidation and Related Reactions. Denis et al.35 synthesized the taxol side chain derivative via Sharpless epoxidation. Starting from cw-cinnamyl alcohol, the corresponding epoxide compound was prepared with 76-80% ee. Subsequent azide ring opening gives a product that possesses the side chain skeleton (Scheme 7-78). 

Wang et al.36 have used the chiral catalyst (DHQ)2 PHAL (see Chapter 4 for the structure) for the asymmetric synthesis of the taxol side chain. Optically enriched diol was obtained at 99% ee via asymmetric dihydroxylation. Sub-... 

Sharpless asymmetric aminohydroxylation can also be used for taxol side chain synthesis. For example, using DHQ as a chiral ligand, asymmetric aminohydroxylation of methyl trau.v-cinnamatc provides compound 240 in high enantiomeric excess (Scheme 7-80).37... 

Mukai et al.39 used a chiral aryl chromium complex to synthesize the taxol side chain via substrate-controlled aldol reaction (Scheme 7-83). 

Commerqon et al.40 developed a method based on an Evans-type auxiliary-controlled aldol reaction. Subsequent treatment of the aldol product with base produced the standard epoxide compound for the asymmetric synthesis of the taxol side chain (Scheme 7-84). 

S.3.2 Via Mannich-Type Reaction. Hattori et al.42 used a Mannich-type reaction for constructing the taxol side chain. In the presence of a BINOL-containing boron compound, the asymmetric Mannich reaction proceeded smoothly, providing the product with good yield (Scheme 7-86). 

Further details of the asymmetric construction of the taxol side chain or related compounds can be found elsewhere.43... 

This chapter has introduced the asymmetric synthesis of several types of natural products erythronolide A, 6-deoxyerythronolide, rifamycin S, prostaglandins and baccatin III, the polycyclic part of taxol, as well as the taxol side chain. The... 

Polyamino acids are easy to prepare by nucleophUe-initiated polymerisation of amino acid JV-carboxyanhydrides. Polymers such as poly-(L)-leucine act as robust catalysts for the epoxi-dation of a wide range of electron-poor alkenes, such as y-substituted a,Ji-unsaturated ketones. The optically active epoxides so formed may be transformed into heterocyclic compounds, polyhydroxylated materials and biologically active compounds such as dUtiazem and taxol side chain. 

Keywords Polyamino acids. Optically active epoxyketones. Synthesis of dUtiazem and taxol side-chain. Asymmetric oxidation. 

A recent synthesis of the phenylisoserine side-chain of taxol is shown in Scheme 18. The enone 21 was obtained in high yield by condensation of benzal-dehyde with pinacolone. Employing the non-aqueous two-phase epoxidation protocol, epoxide 22 was obtained in 76% yield and 94% e.e. Recrystallisation of the epoxide furnished the desired enantiomer in 97 % e. e. Subsequent manipulations of the epoxy-ketone gave the taxol side-chain 23 with the required stereochemistry (Scheme 18). 

This reaction has been applied for the synthesis of the Taxol side chain from the frani-alkene (Rj = Ph, R2 = CH2OAC) (Table 8.20, entry 11, Fig. 8.9 Scheme 8.55). 

Adger, B.M., Barkley, J V. Bergeron, S., Cappi, M.W., Elowerdew, B.E., Jackson, M. R, McCague, R., Nugent, T.C. and Roberts, S.M. Improved Procedure for Julia-Colonna Asymmetric Epoxidation of a,/l-Unsaturated Ketones Total Synthesis of Diltiazem and Taxol Side-chain. J. Chem. Soc., Perkin Trans. 1 1997, 23, 3501-3507. 

Scheme 7.2 Semi-synthetic Taxol side-chain precursor.

A camphor lactam imide auxiliary has also been used in a similar fashion (equation 124)501. Using this type of protocol, but replacing the aldehyde with an imine, the docetaxel (an important anticancer compound related to taxol) side chain has been... 

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