Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis and In Vitro Evaluation of Taxol oxetane ring D precursors.

ABSTRACT: A series of potential taxoid substrates was prepared in radiolabelled form to probe in vitro for the oxirane formation step and subsequent ring expansion step to the oxetane (ring D) presumably involved in the biosynthesis of the anticancer agent Taxol. None of the taxoid test substrates underwent transformation in cell-free systems from Taxus suggesting that these surrogates bore substitution patterns inappropriate for recognition or catalysis by the target enzymes, or that taxoid oxiranes and oxetanes arise by independent biosynthetic pathways.

SUBMITTER: Kaspera R

PROVIDER: S-EPMC2839165 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis and In Vitro Evaluation of Taxol oxetane ring D precursors.

Kaspera Rüdiger R Cape Jonathan L JL Faraldos Juan A JA Ketchum Raymond E B RE Croteau Rodney B RB

Tetrahedron letters 20100401 15

A series of potential taxoid substrates was prepared in radiolabelled form to probe in vitro for the oxirane formation step and subsequent ring expansion step to the oxetane (ring D) presumably involved in the biosynthesis of the anticancer agent Taxol. None of the taxoid test substrates underwent transformation in cell-free systems from Taxus suggesting that these surrogates bore substitution patterns inappropriate for recognition or catalysis by the target enzymes, or that taxoid oxiranes and ...[more]

PMID: 20305723

Similar Datasets

Synthesis of a Spirocyclic Oxetane-Fused Benzimidazole.

Project description:A new synthesis of 2-oxa-7-azaspiro[3.5]nonane is described. Spirocyclic oxetanes, including 2-oxa-6-azaspiro[3.3]heptane were converted into o-cycloalkylaminoacetanilides for oxidative cyclizations using Oxone® in formic acid. The expanded spirocyclic oxetane successfully gave the [1,2-a] ring-fused benzimidazole. X-ray crystal structure of the resultant new tetracyclic system, 1',2'-dihydro-4'H-spiro[oxetane-3,3'-pyrido[1,2-a]benzimidazole] and the azetidine ring-opened adduct, N-(2-acetamido-4-bromophenyl)-N-{[3-(chloromethyl) oxetan-3-yl]methyl}acetamide are disclosed.

| S-EPMC6332447 | biostudies-literature

A mild catalytic synthesis of 2-oxazolines via oxetane ring-opening: rapid access to a diverse family of natural products.

Project description:A new catalytic protocol for the expedient synthesis of oxazolines from oxetanes is disclosed. This mild process complements the conventional oxazoline synthesis based on non-catalytic cyclization of ?-hydroxy or unsaturated amides. It is also a new addition to the reactivity profile of oxetanes leading to heterocycles. In the presence of In(OTf)3, various 3-amido oxetanes underwent smooth intramolecular cyclization to form the corresponding 2-oxazolines, including some valuable oxazoline-based bidentate ligands. This protocol also provides rapid access to various natural products and antibacterial molecules.

| S-EPMC6993743 | biostudies-literature

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions.

Project description:The selective ring-opening reaction of fluoroalkylidene-oxetanes was directed by the presence of the fluorine atom, enabling a two-step access to tetrasubstituted fluoroalkenes with excellent geometry control. Despite its small van der Waals radii electronic, rather than steric influences of the fluorine atom governed the ring-opening reaction with bromide ions, even in the presence of bulky substituents.

| S-EPMC7418098 | biostudies-literature

A hexacyclic ent-trachylobane diterpenoid possessing an oxetane ring from Mitrephora glabra.

Project description:[chemical reaction: see text]. Three new ent-trachylobane diterpenoids (1-3) were isolated and structures elucidated from Mitrephora glabra Scheff. (Annonaceae). Mitrephorone A (1) possesses a hexacyclic ring system with adjacent ketone moieties and an oxetane ring, both of which are unprecedented among trachylobanes. All compounds were evaluated for cytotoxicity against a panel of cancer cells, where 1 displayed the most potent and broadest activity, and against a battery of antimicrobial assays, where all compounds were approximately equipotent.

| S-EPMC2442714 | biostudies-literature

A relay ring-closing metathesis synthesis of dihydrooxasilines, precursors of (Z)-iodo olefins.

Project description:A convenient Grubbs II metathesis provides dihydrooxasilines by relay RCM (RRCM). Dihydrooxasilines undergo ring opening to give Z-vinyl silanes. These can then be converted to Z-vinyl iodides. This sequence provides a short, high yield, and convenient route to trisubstituted Z-vinyl iodides, useful intermediates for the preparation of polypropionate antibiotics.

| S-EPMC2765515 | biostudies-literature

Two-Phase Synthesis of Taxol.

Project description:Taxol (a brand name for paclitaxel) is widely regarded as among the most famed natural isolates ever discovered, and has been the subject of innumerable studies in both basic and applied science. Its documented success as an anticancer agent, coupled with early concerns over supply, stimulated a furious worldwide effort from chemists to provide a solution for its preparation through total synthesis. Those pioneering studies proved the feasibility of retrosynthetically guided access to synthetic Taxol, albeit in minute quantities and with enormous effort. In practice, all medicinal chemistry efforts and eventual commercialization have relied upon natural (plant material) or biosynthetically derived (synthetic biology) supplies. Here we show how a complementary divergent synthetic approach that is holistically patterned off of biosynthetic machinery for terpene synthesis can be used to arrive at Taxol.

| S-EPMC8349513 | biostudies-literature

Rewiring <i>Saccharomyces cerevisiae</i> metabolism for optimised Taxol® precursors production.

Project description:Saccharomyces cerevisiae has been conveniently used to produce Taxol® anticancer drug early precursors. However, the harmful impact of oxidative stress by the first cytochrome P450-reductase enzymes (CYP725A4-POR) of Taxol® pathway has hampered sufficient progress in yeast. Here, we evolved an oxidative stress-resistant yeast strain with three-fold higher titre of their substrate, taxadiene. The performance of the evolved and parent strains were then evaluated in galactose-limited chemostats before and under the oxidative stress by an oxidising agent. The interaction of evolution and oxidative stress was comprehensively evaluated through transcriptomics and metabolite profiles integration in yeast enzyme-constrained genome scale model. Overall, the evolved strain showed improved respiration, reduced overflow metabolites production and oxidative stress re-induction tolerance. The cross-protection mechanism also potentially contributed to better heme, flavin and NADPH availability, essential for CYP725A4 and POR optimal activity in yeast. The results imply that the evolved strain is a robust cell factory for future efforts towards Taxol© production.

| S-EPMC10716015 | biostudies-literature

Enantioselective Synthesis of Caprolactam and Enone Precursors to the Heterocyclic DEFG Ring System of Zoanthenol.

Project description:The enantioselective synthesis of both caprolactam and enone synthons for the DEFG ring system of zoanthenol are described. The evolution of this synthetic approach proceeds first through a synthesis using the chiral pool as a starting point. Challenges in protecting group strategy led to the modification of this approach beginning with (±)-glycidol. Ultimately, an efficient approach was developed by employing an asymmetric hetero-Diels-Alder reaction. The caprolactam building block can be converted by an interesting selective Grignard addition to the corresponding enone synthon. Addition of a model alkyne provides support for the late-stage addition of a hindered alkyne into the caprolactam building block.

| S-EPMC5225988 | biostudies-literature

Seco-B-Ring Steroidal Dienynes with Aromatic D Ring: Design, Synthesis and Biological Evaluation.

Project description:Continuing our structure-activity studies on the vitamin D analogs with the altered intercyclic seco-B-ring fragment, we designed compounds possessing dienyne system conjugated with the benzene D ring. Analysis of the literature data and the docking experiments seemed to indicate that the target compounds could mimic the ligands with a good affinity to the vitamin D receptor (VDR). Multi-step synthesis of the C/D-ring building block of the tetralone structure was achieved and its enol triflate was coupled with the known A-ring fragments, possessing conjugated enyne moiety, using Sonogashira protocol. The structures of the final products were confirmed by NMR, UV and mass spectroscopy. Their binding affinities for the full-length human VDR were determined and it was established that compound substituted at C-2 with exomethylene group showed significant binding to the receptor. This analog was also able to induce monocytic differentiation of HL-60 cells.

| S-EPMC5666843 | biostudies-literature

Design and synthesis of simplified taxol analogs based on the T-Taxol bioactive conformation.

Project description:A series of compounds designed to adopt a conformation similar to the tubulin-binding T-Taxol conformation of the anticancer drug paclitaxel has been synthesized. Both the internally bridged analogs 37-39, 41 and the open-chain analogs 27-29 and 43 were prepared. The bridged analogs 37-39 and 41 were synthesized by Grubbs' metatheses of compounds 30-32 and 33, which, in turn, were prepared by coupling ?-lactams 24-26 with alcohols 22 and 23. Both the bridged and the open-chain analogs showed moderate to good cytotoxicity.

| S-EPMC3225578 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data