Paclitaxel 7-ethers

QHijOjP 122-52-1) see Foscamet sodium Gesirinone 7-O-triethylsilylbaccatin III (C,7H520 Si 115437-21-3) see Paclitaxel 4-triethylsilyl 3-butyn-l-ol triethylsilyl ether (C 4Hj40Si2 160194-28-5) see Rizatriptan benzoate triethylsilyl chloride... 

Walker et al prepared lOa-spiro epoxide (42a) and its 7-methoxymethyl (MOM) ether (42b), which exhibited comparable cytotoxicity and tubulin assembly activity with paclitaxel. 

Chen, S.-H. First syntheses of C-4 methyl ether paclitaxel analogues and the unexpected reactivity of 4-deacetyl-4-methyl ether baccatin III. Tetrahedron Lett., 1996, 37 3935. 

Chen S-H (1996) First Syntheses of C-4 Methyl Ether Paclitaxel Analogs and the Unexpected Reactivity of 4-Deacetyl-4-Methyl Ether Baccatin III. Tetrahedron Lett 37 3935... 

Golik J, Wong HSL, Chen S-H, Doyle TW, Wright JJK, Knipe J, Rose WC, Casazza AM, Vyas DM (1996) Synthesis and Antitumor Evaluation of Paclitaxel Phospho-nooxymethyl Ethers a Novel Class of Water Soluble Paclitaxel Pro-Drugs. Bioorg Med Chem Lett 6 1837... 

Dischino DD, Chen SH, Golik J, Walker DW, Wong HSL (1997) Synthesis of the Monosodium Salt of Carbon-14 Labeled Paclitaxel (Taxol)2 -Ethyl Carbonate 7-Phosphonooxymethyl Ether, a Potential Prodrug of Paclitaxel. J Labelled Compd and Radiopharm 39 173... 

This methodology was then employed to constmct the C, D-ring portion of paclitaxel (581) [178]. In this case, reaction of 574 with DMAD in 5 M ethereal LiC104 produced mainly 575 in 83% yield (Scheme 13.115). This diastereomer 575 was then converted into bicyclic lactone 576 in several steps. Further transformations produced oxabicycle 577 wherein three of the five requisite stereocenters are set. Ring opening and manipulation of the oxidation states of 578 afforded 579. This was followed by an intramolecular cyclization to produce the oxetane ring present in 580. 

The first catalytic enantioselective Mannich reaction was documented by Kobayashi, using the conveniently assembled BINOL-derived Zr catalyst 212 (Scheme 11.32) [150]. This catalyst was highly effective in enantioselective additions of silyl ketene acetals to N-(o-hydroxyphenyl)-aldimines such as 210. In a further expansion of the reaction scope, ( )- and (Z)-substituted a-alkoxy silyl enol ethers were observed to undergo diastereoselective additions to aldimines, giving syn and anti amino alcohols, respectively [151]. These processes were utilized in the rapid assembly of (2R,3S)-3-phenyliso-serine (214), a precursor of the C,3 side chain of paclitaxel, known to be essential for its anticancer activity. 

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