Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Biomimetic Total Synthesis and Investigation of the Non-Enzymatic Chemistry of Oxazinin A.

ABSTRACT: We report the first total synthesis of an antimycobacterial natural product oxazinin A that takes advantage of a multi-component cascade reaction of anthranilic acid and a precursor polyketide containing an aldehyde. The route utilized for the synthesis of the pseudodimeric oxazinin A validates a previously proposed biosynthetic mechanism, invoking a non-enzymatic pathway to the complex molecule. We found a 76 : 10 : 9 : 5 ratio of oxazinin diastereomers from the synthetic cascade, which is an identical match to that found in the fermentation media from the fungus Eurotiomycetes 110162. Further investigation of the non-enzymatic formation of oxazinin A using ¹ H-¹⁵ N HMBC NMR spectroscopy allowed for a plausible determination of the stepwise mechanism. The developed route is highly amenable for the synthesis of diverse sets of analogs around the oxazinin scaffold to study structure-activity relationships (SAR).

SUBMITTER: Aniebok V

PROVIDER: S-EPMC9479274 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Biomimetic Total Synthesis and Investigation of the Non-Enzymatic Chemistry of Oxazinin A.

Aniebok Victor V Shingare Rahul D RD Wei-Lee Hsiau H Johnstone Timothy C TC MacMillan John B JB

Angewandte Chemie (International ed. in English) 20220816 38

We report the first total synthesis of an antimycobacterial natural product oxazinin A that takes advantage of a multi-component cascade reaction of anthranilic acid and a precursor polyketide containing an aldehyde. The route utilized for the synthesis of the pseudodimeric oxazinin A validates a previously proposed biosynthetic mechanism, invoking a non-enzymatic pathway to the complex molecule. We found a 76 : 10 : 9 : 5 ratio of oxazinin diastereomers from the synthetic cascade, which is an i ...[more]

PMID: 35881566

Similar Datasets

Biomimetic Total Synthesis of Enterocin.

Project description:The first chemical total synthesis of the highly oxygenated polyketide enterocin has been accomplished. The key step of the synthesis was a late-stage biomimetic reaction cascade involving two intramolecular aldol reactions in which each step proceeded in 52 % yield (averaged) and which established four of the seven stereogenic centers. The pivotal precursor for the cascade reaction was assembled from three readily available building blocks. A chiral dithioacetal with two stereogenic centers originating from L-arabinose represented the core fragment to both ends of which the other building blocks were attached by aldol reactions. The remaining stereogenic center was installed by Davis oxygenation immediately prior to the key step.

| S-EPMC8457242 | biostudies-literature

Biomimetic total synthesis of malbrancheamide and malbrancheamide B.

Project description:The biomimetic total syntheses of both malbrancheamide and malbrancheamide B are reported. The synthesis of the two monochloro species enabled the structure of malbrancheamide B to be unambiguously assigned. The syntheses each feature an intramolecular Diels-Alder reaction of a 5-hydroxypyrazin-2(1H)-one to construct the bicyclo[2.2.2]diazaoctane core, which has also been proposed as the biosynthetic route to these compounds.

| S-EPMC2837585 | biostudies-literature

Chemo-enzymatic total synthesis of the spirosorbicillinols.

Project description:The natural product class of the sorbicillinoids is composed of structurally diverse molecules with many strong, biomedically relevant biological activities. Owing to their complex structures, the synthesis of sorbicillinoids is a challenging task. Here we show the first total synthesis of the fungal sorbicillinoids spirosorbicillinols A-C. The convergent route comprises the chemo-enzymatic transformation of sorbicillin to the highly reactive sorbicillinol and the assembly of scytolide and isomers starting from shikimic and quinic acid analogs. The key step in the total synthesis is the fusion of both building blocks in a Diels-Alder cycloaddition leading to the straightforward formation of the characteristic sorbicillinoid bicyclo[2.2.2]octane backbone. This work provides unifying access to all natural spirosorbicillinols and unnatural diastereomers.

| S-EPMC10482909 | biostudies-literature

Merging enzymatic and synthetic chemistry with computational synthesis planning.

Project description:Synthesis planning programs trained on chemical reaction data can design efficient routes to new molecules of interest, but are limited in their ability to leverage rare chemical transformations. This challenge is acute for enzymatic reactions, which are valuable due to their selectivity and sustainability but are few in number. We report a retrosynthetic search algorithm using two neural network models for retrosynthesis-one covering 7984 enzymatic transformations and one 163,723 synthetic transformations-that balances the exploration of enzymatic and synthetic reactions to identify hybrid synthesis plans. This approach extends the space of retrosynthetic moves by thousands of uniquely enzymatic one-step transformations, discovers routes to molecules for which synthetic or enzymatic searches find none, and designs shorter routes for others. Application to (-)-Δ9 tetrahydrocannabinol (THC) (dronabinol) and R,R-formoterol (arformoterol) illustrates how our strategy facilitates the replacement of metal catalysis, high step counts, or costly enantiomeric resolution with more elegant hybrid proposals.

| S-EPMC9750992 | biostudies-literature

Convergent and Biomimetic Enantioselective Total Synthesis of (-)-Communesin F.

Project description:The first biomimetic enantioselective total synthesis of (-)-communesin F based on a late-stage heterodimerization and aminal exchange is described. Our synthesis features the expedient diazene-directed assembly of two advanced fragments to secure the congested C3a-C3a' linkage in three steps, followed by a highly efficient biogenetically inspired aminal reorganization to access the heptacyclic communesin core in only two additional steps. Enantioselective syntheses of the two fragments were developed, with highlights including the catalytic asymmetric halocyclization and diastereoselective oxyamination reactions of tryptamine derivatives, a stereoselective sulfinimine allylation, and an efficient cyclotryptamine-C3a-sulfamate synthesis by either a new silver-promoted nucleophilic amination or a rhodium-catalyzed C-H amination protocol. The versatile syntheses of the fragments, their stereocontrolled assembly, and the efficient aminal exchange as supported by in situ monitoring experiments, in addition to the final stage N1'-acylation of the communesin core, provide a highly convergent synthesis of (-)-communesin F.

| S-EPMC4944760 | biostudies-literature

Efficient Biomimetic Total Synthesis, Characterization, and Antioxidant Activity of Ommatins.

Project description:Ommatins, natural colorants found in cephalopods and arthropods, are biosynthesized from tryptophan with uncyclized xanthommatin (Uc-Xa) as the key biosynthetic precursor. These pigments change color under oxidative or reductive conditions. Xanthommatin (Xa) and dihydro-xanthommatin (H2-Xa), as well as decarboxylated xanthommatin (Dc-Xa) and decarboxylated-dihydro-xanthommatin (Dc-H2-Xa), are some of the most common and well-studied ommatins. Herein, we describe the biomimetic total synthesis of Xa/H2-Xa on a gram scale by using the Mannich reaction and oxidative dimerization as the key steps. The 7-step linear synthetic sequence achieved an overall yield of 27%. Dc-Xa/Dc-H2-Xa and protected Uc-Xa/Uc-H2-Xa were also synthesized from the common intermediate-protected 3-hydroxykynurenine (3-OHK). The synthesized ommatins underwent thorough characterization using various spectroscopic techniques, including NMR, UV-vis, FTIR, HRMS, and LC-MS. Their optoelectronic properties were studied using spectrophotometry and electrochemical analysis. Furthermore, the antioxidant activity of the synthesized ommatins was evaluated using an oxygen radical antioxidant capacity activity assay. The results indicated that Dc-Xa exhibited the highest antioxidant activity, followed by Xa, while Uc-Xa showed the lowest activity.

| S-EPMC11600184 | biostudies-literature

Biomimetic total synthesis of the reported structure of (+)-selaginedorffone B.

Project description:The first enantioselective total synthesis of the reported structure of the structurally unique aromatic tetraterpenoid of anti-cancer potential, (+)-selaginedorffone B (2), has been accomplished from two modified abietane diterpenoids through an intermolecular Diels-Alder reaction between a bio-inspired diene 3 (HOMO counterpart) and dienophile 4 (corresponding LUMO counterpart) in a 23-step sequence, whereas the core framework of the monomeric abietane diterpenoid was constructed via alkyne-activated ene-cyclization. Computational analysis was conducted to reveal the intricate regio and diastereoselectivity of this novel Diels-Alder reaction, strengthening the experimental results. The absolute configuration of the synthesized molecule was validated through X-ray studies of late-stage intermediates as well as comprehensive 2D NMR analysis.

| S-EPMC11376052 | biostudies-literature

Enzymatic total synthesis of rabelomycin, an angucycline group antibiotic.

Project description:A one-pot enzymatic total synthesis of angucycline antibiotic rabelomycin was accomplished, starting from acetyl-CoA and malonyl-CoA, using a mixture of polyketide synthase (PKS) enzymes of the gilvocarcin, ravidomycin, and jadomycin biosynthetic pathways. The in vitro results were compared to in vivo catalysis using analogous sets of enzymes.

| S-EPMC2895501 | biostudies-literature

Biomimetic Total Synthesis of (±)-Griffipavixanthone via a Cationic Cycloaddition-Cyclization Cascade.

Project description:We report the concise, biomimetic total synthesis of the dimeric, Diels-Alder natural product griffipavixanthone from a readily accessible prenylated xanthone monomer. The key step utilizes a novel intermolecular [4+2] cycloaddition-cyclization cascade between a vinyl p-quinone methide and an in situ generated isomeric diene promoted by either Lewis or Brønsted acids. Experimental and computational studies of the reaction pathway suggest that a stepwise, cationic Diels-Alder cycloaddition is operative.

| S-EPMC5718057 | biostudies-literature

Total Synthesis and Pharmacological Investigation of Cordyheptapeptide A.

Project description:The present investigation reports the synthesis of a phenylalanine-rich N-methylated cyclopeptide, cordyheptapeptide A (8), previously isolated from the insect pathogenic fungus Cordyceps sp. BCC 1788, accomplished through the coupling of N-methylated tetrapeptide and tripeptide fragments followed by cyclization of the linear heptapeptide unit. Structure elucidation of the newly synthesized cyclopolypeptide was performed by means of FT-IR, ¹H-NMR, 13C-NMR, and fast atom bombardment mass spectrometry (FABMS), and screened for its antibacterial, antidermatophytic, and cytotoxic potential. According to the antimicrobial activity results, the newly synthesized N-Methylated cyclopeptide exhibited potent antibacterial activity against Gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae and antifungal activity against dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 μg/mL, in comparison to the reference drugs, gatifloxacin and griseofulvin. In addition, cyclopolypeptide 8 displayed suitable levels of cytotoxicity against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines.

| S-EPMC6152760 | 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