150541-99-4Relevant articles and documents
Taxol structure-activity relationships: Synthesis and biological evaluation of 2-deoxytaxol
Chen,Wei,Farina
, p. 3205 - 3206 (1993)
2-Deoxy taxol 2 was prepared in nine steps from baccatin III; the key step of the synthesis is a Barton-type deoxygenation at C-2. The compound was found to possess much reduced antitumor activity with respect to taxol.
Total Synthesis of Paclitaxel
Iiyama, Shota,Fukaya, Keisuke,Yamaguchi, Yu,Watanabe, Ami,Yamamoto, Hiroaki,Mochizuki, Shota,Saio, Ryosuke,Noguchi, Takashi,Oishi, Takeshi,Sato, Takaaki,Chida, Noritaka
, p. 202 - 206 (2021/12/27)
The total synthesis of paclitaxel (Taxol) is described. Double Rubottom oxidation of the bis(silyl enol ether) derived from a tricarbocyclic diketone effectively installed a bridgehead olefin and C-5/C-13 hydroxy groups in a one-step operation. The novel Ag-promoted oxetane formation smoothly constructed the tetracyclic framework of paclitaxel.
Synthesis of 4-deacetyl-1-dimethylsilyl-7-triethylsilylbaccatin III
Ondari, Mark E.,Walker, Kevin D.
experimental part, p. 2186 - 2188 (2009/08/07)
A one-pot trisilylation step to protect three hydroxyl groups of baccatin III (1), followed by hydride ester cleavage and base hydrolysis of a triethylsilyl ether at C13, provides efficient access to a key intermediate 9 (top path). This route removes two
The taxol pathway 10-O-acetyltransferase shows regioselective promiscuity with the oxetane hydroxyl of 4-deacetyltaxanes
Ondari, Mark E.,Walker, Kevin D.
experimental part, p. 17187 - 17194 (2009/04/13)
The 10-deacetylbaccatin III:10β-O-acetyltransferase isolated from Taxus cuspidata regiospecifically transfers short-chain alkanoyl groups from their corresponding CoA thioesters to the C10 hydroxyl of 10-deacetylbaccatin III. This 10-O-acetyltransferase along with five other Taxus acyltransferases on the paclitaxel (Taxol) biosynthetic pathway and one additional Taxus-derived acyltransferases of unknown function were screened for 4-O-acetyltransferase activity against 4-deacetylbaccatin III, 7-acetyl-, 13-acetyl-, and 7,13-diacetyl-4-deacetylbaccatin III. These 4-deacyl derivatives were semisynthesized from the natural product baccatin III via silyl protecting group manipulation, regioselective reductive ester cleavage with sodium bis(2-methoxyethoxy)aluminum hydride, and regioselective acetylation with acetic anhydride. Assays with the 4-deacetylated diterpene substrates and acetyl CoA revealed the taxane 10β-O-acetyltransferase was able to catalyze the 4-O-acetylation of 4-deacetylbaccatin III to baccatin III and 13-acetyl-4-deacetylbacatin III to 13-acetylbaccatin III, although each was converted at lesser efficiency than with the natural substrate. In contrast, this enzyme was unable to acetylate 7-acetyl-4-deacetylbaccatin III and 7,13-diacetyl-4-deacetylbaccatin III substrates at C4, suggesting that the C7 hydroxyl of baccatin III must remain deacylated for enzyme function. The biocatalytic transfer of an acyl group to the tertiary hydroxyl on the oxetane moiety at C4 of the taxane ring demonstrates that the regiochemistry of the 10β-acetyltransferase is mutable.
Asymmetric total synthesis of Taxol
Mukaiyama, Teruaki,Shiina, Isamu,Iwadare, Hayato,Saitoh, Masahiro,Nishimura, Toshihiro,Ohkawa, Naoto,Sakoh, Hiroki,Nishimura, Koji,Tani, Yu-Ichirou,Hasegawa, Masatoshi,Yamada, Koji,Saitoh, Katsuyuki
, p. 121 - 161 (2007/10/03)
The asymmetric total synthesis of Taxol was achieved by way of B to BC to ABC to ABCD ring construction. Optically active 8-membered ring enones 1 and 2 corresponding to the B ring of Taxol have been synthesized in high yields from the linear precursors 28 and 32, respectively, by intramolecular aldol cyclization using SmI2. The optically active linear polyoxy compounds 28 and 32 were obtained by way of diastereoselective aldol reaction between aldehyde 4 and ketene silyl acetal 8 catalyzed by MgBr2 · OEt2. The chiral pentanal 4 was synthesized either by asymmetric aldol reaction of achiral aldehyde 7 and ketene silyl acetal 8 by means of a chiral Lewis acid or by diastereoselective aldol reaction between the chiral aldehyde 16, derived from L-serine, and the lithium enolate derived from methyl isobutyrate. Optically active bicyclo[6.4.0]dodecanone 38β, corresponding to the BC ring system of Taxol, was prepared from 8-membered ring enone 2 in high yield by stereoselective Michael addition and successive intramolecular aldol cyclization. Furthermore, baccatin III, the ABCD ring system of Taxol, was efficiently synthesized from the BC ring system 38β by successive construction of the A and D rings by intramolecular pinacol coupling cyclization, introduction of the C-13 hydroxyl group and an oxetane-forming reaction. Finally, the total synthesis of Taxol was accomplished by dehydration condensation between a protected N-benzoylphenylisoserine 70 or 75 and 7-TES baccatin III, prepared from baccatin III. Taxol side chains 70, 73, 75, and 77, optically active protected N-benzoylphenylisoserines, were synthesized by enantioselective aldol reaction from two achiral starting materials, benzaldehyde and an enol silyl ether 65 derived from S-ethyl benzyloxyethanethioate.
A new method for the synthesis of baccatin III
Shiina, Isamu,Iwadare, Hayato,Sakoh, Hiroki,Hasegawa, Masatoshi,Tani, Yu-Ichirou,Mukaiyama, Teruaki
, p. 1 - 2 (2007/10/03)
Baccatin III was efficiently synthesized from the BC ring system of Taxol, 2α,10β-dibenzyloxy-11β-(t-butyldimethylsiloxy)-7β-hydroxy- 1α-(4-methoxybenzyloxy)-8β,15,15-trimethyl-4-methylene-trans- bicyclo[6.4.0]dodecan-9-one (1), by successive constructions of A and D rings via respective intramolecular pinacol coupling and oxetane forming reaction.
New and effective synthesis of 7-triethylsilylbaccatin III from 7β,13α-bistriethylsiloxy-1β,2α,10β-trihydroxy-9-oxo- 4(20),11-taxadiene
Shiina, Isamu,Saitoh, Masahiro,Nishimura, Koji,Saitoh, Katsuyuki,Mukaiyama, Teruaki
, p. 223 - 224 (2007/10/03)
7β,13α-Bistriethylsiloxy-1β,2α,10β-trihydroxy -9- oxo-4(20), 11-taxadiene (2), derived from 10-deacetylbaccatin III via degradation of oxetane ring, was conveniently converted into 7-triethylsilylbaccatin III (1) by way of a new and effective method for constructing oxetane ring. Thus, the synthesis of a precursor of taxol from novel taxoid 2 was accomplished.
Crystal structure of 2-debenzoyl, 2-acetoxy paclitaxel (Taxol): Conformation of the paclitaxel side-chain
Gao,Wei,Chen
, p. 337 - 341 (2007/10/03)
Crystals of the C2-acetate analog of paclitaxel, grown from a mixture of isopropyl alcohol and methanol, belong to the space group P21 with a = 9.058(3), b = 18.306(5), c = 15.043(1) A, β = 97.09(1)°, Z = 2, V = 2475.1(9)A3, D(calc) = 1.269 gcm-3 and μ = 0.75 cm-1. The structure was determined by direct methods and refined to R(E) = 0.054 and wR(F) = 0.057 for 605 variables and 3496 observed reflections. The paclitatxel side chain possesses a conformation similar to that observed in the crystal structure of docetaxel (Taxotere). A three dimensional network of hydrogen bonds is formed through solvent molecules and stabilizes the crystal lattice.
The Chemistry of Taxanes: Skeletal Rearrangements of Baccatin Derivatives via Radical Intermediates
Chen, Shu-Hui,Huang, Stella,Gao, Qi,Golik, Jerzy,Farina, Vittorio
, p. 1475 - 1484 (2007/10/02)
In the course of a synthetic program aimed at systematic defunctionalization of the taxol core for structure activity studies, a number of radical-based deoxygenation reactions were carried out on baccatin III derivatives.In this connection, we have discovered that formation of radicals at positions C-1, C-2, and C-7 in the taxane core of baccatin III results in a number of skeletal rearrangement cascades.Furthermore, the exact composition of the product mixture depends on the specific tin (or silicon) hydride used for the reduction.In the case of C-2 and C-7-derived radicals, direct quenching with tin hydrides without rearrangement was possible under some conditions.However, we were unable to find conditions to quench the C-1 radical, since rearrangement pathways always predominate in this case.
