Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Total synthesis, structure revision and cytotoxic activity of Sch 53825 and its derivatives† † Electronic supplementary information (ESI) available. CCDC 2169161. For ESI and crystallographic data in CIF or other electronic format see https://doi.org/10.1039/d2ra02898k

ABSTRACT: The first total synthesis of Sch 53825 (14) was achieved in 12 steps from 5-hydroxy-1-tetralone in 16% overall yield through N-benzyl cinchoninium chloride-catalyzed asymmetric epoxidation and a Mitsunobu reaction as the key steps. On this basis, the synthesis of palmarumycin B6 was improved using the same raw material with 6 steps and 32% overall yield. Also, three new analogues with two chlorine atoms were synthesized. Their structures were characterized by 1H, 13C NMR, HR-ESI-MS and X-ray diffraction data. The structure of natural Sch 53825 was revised as an epimer of compound 1 with the anti-hydroxy epoxide at C-4. Their cytotoxic activities against several tumor cell lines (HCT116, U251, BGC823, Huh-7 and PC9) showed that compound 11 exhibited excellent cytotoxicity against above mentioned cancer cell lines with IC50 < 0.5 μM. The first total synthesis of Sch 53825 (14) was achieved in 12 steps from 5-hydroxy-1-tetralone in 16% overall yield through N-benzyl cinchoninium chloride-catalyzed asymmetric epoxidation and a Mitsunobu reaction as the key steps.

SUBMITTER: Xu L

PROVIDER: S-EPMC9194939 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Total synthesis of (+)-SCH 351448.

Project description:A convergent synthesis of (+)-SCH 351448 (1), a monosodium salt of a C(2)-symmetric macrodiolide, is described. Our approach is based on a [4 + 2] annulation with a chiral allyl silane (anti-5c) to assemble the pyran subunits. Homodimerization was carried out in a stepwise fashion; initial esterification at C29' followed by macrocyclization at C29 afforded the desired macrodiolide.

| S-EPMC3164292 | biostudies-literature

Total Synthesis and Structure Revision of Halioxepine.

Project description:The first total synthesis of halioxepine is accomplished using a 1,4-addition for constructing the quaternary center at C10 and a halo etherification for the generation of the tertiary ether at C7. The correct structure of halioxepine was determined by assembling different enantiomeric building blocks and by changing the relative configuration between C10 and C15.

| S-EPMC7898713 | biostudies-literature

Enhanced Cytotoxic Activity of PEGylated Curcumin Derivatives: Synthesis, Structure-Activity Evaluation, and Biological Activity.

Project description:Curcumin has been modified in various ways to broaden its application in medicine and address its limitations. In this study, we present a series of curcumin-based derivatives obtained by replacing the hydroxy groups in the feruloyl moiety with polyethylene glycol (PEG) chains and the addition of the BF2 moiety to the carbonyl groups. Tested compounds were screened for their cytotoxic activity toward two bladder cancer cell lines, 5637 and SCaBER, and a noncancerous cell line derived from lung fibroblasts (MRC-5). Cell viability was analyzed under normoxic and hypoxic conditions (1% oxygen). Structure-activity relationships (SARs) are discussed, and curcumin derivatives equipped within feruloyl moieties with 3-methoxy and 4-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy} substituents (5) were selected for further analysis. Compound 5 did not affect the viability of MRC-5 cells and exerted a stronger cytotoxic effect under hypoxic conditions. However, the flow cytometry studies showed that PEGylation did not improve cellular uptake. Another observation was that the lack of serum proteins limits the intracellular uptake of curcumin derivative 5. The preliminary mechanism of action studies indicated that compound 5 under hypoxic conditions induced G2/M arrest in a dose-dependent manner and increased the expression of stress-related proteins such as p21/CIP1, phosphorylated HSP27, ADAMTS-1, and phosphorylated JNK. In summary, the results of the studies indicated that PEGylated curcumin is a more potent compound against bladder cancer cell lines than the parent compound, and derivative 5 is worthy of further investigation to clarify its mechanism of anticancer action under hypoxic conditions.

| S-EPMC9867315 | biostudies-literature

Total Synthesis and Structure Revision of Diplobifuranylone B.

Project description:An asymmetric total synthesis of diplobifuranylone B was achieved in 10 steps for the longest linear sequence and in 15.8% overall yield from commercially available methyl (R)-(+)-lactate and l-glutamic acid. This synthesis features a stereoselective construction of the key 2,5-dihydrofuran ring in the natural product via a recently developed asymmetric gold catalysis. The stereochemical flexibility offered by the catalysis enables an expedient revision of the reported structure of diplobifuranylone B, where the relative stereochemistry of the 2,5-dihydrofuran moiety was previously misassigned as cis instead of trans.

| S-EPMC7386208 | biostudies-literature

Semi-Synthesis, Cytotoxic Evaluation, and Structure-Activity Relationships of Brefeldin A Derivatives with Antileukemia Activity.

Project description:Brefeldin A (1), a potent cytotoxic natural macrolactone, was produced by the marine fungus Penicillium sp. (HS-N-29) from the medicinal mangrove Acanthus ilicifolius. Series of its ester derivatives 2-16 were designed and semi-synthesized, and their structures were characterized by spectroscopic methods. Their cytotoxic activities were evaluated against human chronic myelogenous leukemia K562 cell line in vitro, and the preliminary structure-activity relationships revealed that the hydroxy group played an important role. Moreover, the monoester derivatives exhibited stronger cytotoxic activity than the diester derivatives. Among them, brefeldin A 7-O-2-chloro-4,5-difluorobenzoate (7) exhibited the strongest inhibitory effect on the proliferation of K562 cells with an IC50 value of 0.84 µM. Further evaluations indicated that 7 induced cell cycle arrest, stimulated cell apoptosis, inhibited phosphorylation of BCR-ABL, and thereby inactivated its downstream AKT signaling pathway. The expression of downstream signaling molecules in the AKT pathway, including mTOR and p70S6K, was also attenuated after 7-treatment in a dose-dependent manner. Furthermore, molecular modeling of 7 docked into 1 binding site of an ARF1-GDP-GEF complex represented well-tolerance. Taken together, 7 had the potential to be served as an effective antileukemia agent or lead compound for further exploration.

| S-EPMC8777696 | biostudies-literature

Synthesis, Structure and Cytotoxic Activity of Mono- and Dialkoxy Derivatives of 5,8-Quinolinedione.

Project description:A series of 5,8-quinolinedione derivatives containing one or two alkoxy groups was synthesized and characterized by ¹H- and (13)C-NMR, IR and MS spectra. X-ray diffraction was used to investigate the crystal structures of 6-chloro-7-(2-cyjanoethoxy)-5,8-quinolinedione and 6,7-di(2,2,2-trifloroethoxy)-5,8-quinolinedione. All studied compounds were tested in vitro for their antiproliferative activity against three human cancer cell lines and human normal fibroblasts. Most of the compounds showed higher cytotoxicity than the starting compound, 6,7-dichloro-5,8-quinolinedione, and cisplatin, which was used as a reference agent.

| S-EPMC6273037 | biostudies-literature

Total synthesis, structure revision, and absolute configuration of (-)-brevenal.

Project description:Total synthesis of structure 1 originally proposed for brevenal, a nontoxic polycyclic ether natural product isolated from the Florida red tide dinoflagellate, Karenia brevis, was accomplished. The key features of the synthesis involved (i) convergent assembly of the pentacyclic polyether skeleton based on our developed Suzuki-Miyaura coupling chemistry and (ii) stereoselective construction of the multi-substituted (E,E)-dienal side chain by using copper(I) thiophen-2-carboxylate (CuTC)-promoted modified Stille coupling. The disparity of NMR spectra between the synthetic material and the natural product required a revision of the proposed structure. Detailed spectroscopic comparison of synthetic 1 with natural brevenal, coupled with the postulated biosynthetic pathway for marine polyether natural products, suggested that the natural product was most likely represented by 2, the C26 epimer of the proposed structure 1. The revised structure was finally validated by completing the first total synthesis of (-)-2, which also unambiguously established the absolute configuration of the natural product.

| S-EPMC2575246 | biostudies-literature

Total Synthesis of the Alleged Structure of Crenarchaeol Enables Structure Revision*.

Project description:Crenarchaeol is a glycerol dialkyl glycerol tetraether lipid produced exclusively in Archaea of the phylum Thaumarchaeota. This membrane-spanning lipid is undoubtedly the structurally most sophisticated of all known archaeal lipids and an iconic molecule in organic geochemistry. The 66-membered macrocycle possesses a unique chemical structure featuring 22 mostly remote stereocenters, and a cyclohexane ring connected by a single bond to a cyclopentane ring. Herein we report the first total synthesis of the proposed structure of crenarchaeol. Comparison with natural crenarchaeol allowed us to propose a revised structure of crenarchaeol, wherein one of the 22 stereocenters is inverted.

| S-EPMC8361987 | biostudies-literature

Revision of the Structure and Total Synthesis of Topsentin C

Project description:An efficient synthetic approach to access (indol-3-yl)ethane-1,2-diamines with a protecting group at the indole N atom from readily available 3-(2-nitrovinyl)indoles is reported. This approach includes solvent-free conjugate addition of

| S-EPMC6193241 | biostudies-literature

Assignment of absolute configuration to SCH 351448 via total synthesis.

Project description:The synthesis and absolute configuration of SCH 351448, an interesting ionophoric natural product, are reported herein. Mukaiyama aldol-Prins and segment-coupling Prins reactions were employed to construct the constituent tetrahydropyrans of SCH 351448. Efforts to assemble the C2-symmetric core of the natural product by a templated olefin metathesis strategy are described; however, a stepwise fragment assembly was ultimately utilized to complete the target molecule.

| S-EPMC2574719 | 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