2 -Methoxy taxol

It would be interesting to learn whether 4,5-dihydro-5 a-hydroxy-4 a-methoxy-6a,12a-dehydro-a-toxicarol interferes with the enzymatic activity of topoisomerase. Note that taxol, a successful chemotherapeutic agent that hampers the normal microtubule machinery, has been suggested to involve additional cytotoxic pathways including p53-independent apoptosis of tumor cells and inhibition of topoisomerase II (42). 

Kim, S.Y. Lee, Y.M. Taxol-loaded block copolymer nanospheres composed of methoxy poly(ethylene glycol) and 70. poly(e-caprolactone) as novel anticancer drug carriers. Biomaterials 2001, 22, 1697-1704. 

Zhang X, Burt HM. Diblock copolymers of poly(dl-lactide-block-methoxy polyethylene glycol) as micellar carriers of taxol. Pharm Res 1995 12 S-265. 

Intermolecular cycloaddition of n-butyl-2-pyridone and 4-methoxy-2-pyridone gives 17 in 51% yield (Figure 1)P This has provided a platform to explore the reactivity of the photoproducts. A combination of the n-butyl substituent and an absence of symmetry results in good solubility properties for 17 compared with many simple pyridone photodimers. Some initial transformations of 17 are shown in Figure 31. In all cases the yields exceed 70% and in most cases are nearly quantitative. The simplest reaction is hydrogenation. The close analogy of 17 to the core of taxol intermediate 53 (Figures 18... 

Recently, Ueno et al used the chiral zirconium catalyst 7.4.4 for asymmetric induction. Thus, reaction of imine 7.4.5 and silyl enol ether 7.4.6 in the presence of 10 mol% S-IAA gave the desired phenyl isoserine derivative 7.4.7 in 94% ee and 95% yield. The a-hydroxy-phenylamine which was required for the catalytic asymmetric induction was then cleaved oxidatively using CAN after being converted to an a-methoxy-phenylamine derivative. Aqueous hydrolysis of the resulting aminoester 7.4.8 yielded the amino acid quantitatively, which was benzoylated to give the taxol side chain (269). 

Several novel carbohydrate-derived ketones have been reported. Arabinose-derived ketone catalyst 16a has been shown to provide good enantioselectivities for the epoxidation of trans-aliphatic alkenes but offered poor enantioselectivity for cis-alkenes [69-71]. Studies found that increased enantioselectivities could be achieved for the epoxidation of dx-alkenes with decreased size of the acetal blocking groups. The best results for the epoxidation of ds-alkenes were found with methoxy catalyst 16b, which was successfully used in the synthesis of the side chain of Taxol [72]. 

Wender, P. A. and RawUns. D. B., Toward the synthesis of the taxol C,D ring system photolysis of a-methoxy ketones. Tetrahedron, 48, 7033,1992. 

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