Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Toward the Total Synthesis of Alpkinidine: Synthesis of Haloquinone CE Ring System Synthons and Attempted Nucleophilic Bisannulation.

ABSTRACT: Model chemistry involving the bisannulation of 2,3-dichloro-1,4-naphthoquinone with the ester enolate derived from ethyl o-nitrophenylacetic acid, which rapid assembled the ABCD ring system of a pentacyclic pyrroloacridine, has been applied to the attempted synthesis of the marine natural product alpkinidine. The reaction of ethyl o-nitrophenylacetic acid with 6,7-dichloro-2-methylisoquinoline-1,5,8(2H)-trione, required to extend the model strategy to alpkinidine, was unfruitful, giving only complex mixtures. Efforts to direct the regiochemistry of the key Michael substitution step using 6-bromo-2-methylisoquinoline-1,5,8(2H)-trione afforded an adduct sharing the complete carbon skeleton of alpkinidine, but this could not be elaborated to the natural product.

SUBMITTER: Buccini M

PROVIDER: S-EPMC9202046 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Toward the Total Synthesis of Alpkinidine: Synthesis of Haloquinone CE Ring System Synthons and Attempted Nucleophilic Bisannulation.

Buccini Marco M Tham Louisa L Dhoro Francis F Skelton Brian W BW Williams Craig M CM Piggott Matthew J MJ

ACS omega 20220601 23

Model chemistry involving the bisannulation of 2,3-dichloro-1,4-naphthoquinone with the ester enolate derived from ethyl o-nitrophenylacetic acid, which rapid assembled the ABCD ring system of a pentacyclic pyrroloacridine, has been applied to the attempted synthesis of the marine natural product alpkinidine. The reaction of ethyl o-nitrophenylacetic acid with 6,7-dichloro-2-methylisoquinoline-1,5,8(2H)-trione, required to extend the model strategy to alpkinidine, was unfrui ...[more]

PMID: 35721899

Similar Datasets

Toward the Total Synthesis of Alpkinidine: Michael Addition to Isoquinolinetrione CE Ring-System Synthons.

Project description:Strategies toward the total synthesis of the marine pyrroloacridine alkaloid alpkinidine have been explored, focusing on linking quinonoid CE ring-system synthons with the A ring, followed by condensation to form the B and D rings. The key Michael addition of the ester enolate derived from ethyl o-nitrophenylacetate to 2-methylisoquinoline-1,5,8(2H)-trione proceeded with the wrong regiochemistry. This issue was addressed by incorporating the D-ring nitrogen at an earlier stage, affording advanced intermediates possessing the complete carbon skeleton of alpkinidine. However, attempts to close the D and B rings were unsuccessful. The novel isoquinolinetriones reported here, and the general strategy of connecting CE- and A-ring synthons through Michael additions, may be useful in the synthesis of other pyrrolo- and pyridoacridines, in particular the anticancer lead neoamphimedine and analogues.

| S-EPMC9202020 | biostudies-literature

Toward the synthesis of cobyric acid. Enantioselective syntheses of completely differentiated ring D synthons.

Project description:Alkyne acids 11 were prepared in an enantioselective fashion from allylic ester derivatives 18 or 20 by Ireland-Claisen rearrangement, followed by Si-assisted elimination of HBr. The title compounds are attractive ring D synthons for an ongoing synthesis of cobyric acid.

| S-EPMC2575186 | biostudies-literature

Orthogonally Protected Diaminocyclopentenones as Synthons: Total Synthesis of (±)-Agelastatin A.

Project description:Natural products containing aminocyclopentanes are common secondary metabolites, often biologically active. This work aims at the preparation of a useful synthon for total synthesis containing orthogonally protected amines. To this end, furfural and two amines were employed to form mixed trans-4,5-diaminocyclopentenones promoted by Cu(OTf)2. The selected amines can be orthogonally deprotected, allowing selective modification of the amines on the cyclopentane core. Their utility was showcased for the total synthesis of highly complex (±)-Agelastatin A.

| S-EPMC10262273 | biostudies-literature

Studies toward the total synthesis of dihydrolycolucine. Preparation of AB and CEF ring fragments.

Project description:A strategy for the synthesis of the lycopodium alkaloid dihydrolycolucine (1) has been investigated. Synthetic routes were developed based on N-acylpyridinium salt chemistry to prepare target fragments 3 and 4 that could ultimately converge to the natural product. Key reactions include IMDA cycloadditions and retro-Mannich ring-openings to form both the AB and the EF ring fragments. The ring C precursor was prepared using pyridine substitution and directed lithiation chemistry. A Suzuki cross-coupling of rings C and EF led to the CEF ring fragment. Initial attempts at closure of the seven-membered D ring were unsuccessful.

| S-EPMC4066915 | biostudies-literature

Chemically Recyclable Polymer System Based on Nucleophilic Aromatic Ring-Opening Polymerization.

Project description:The development of chemically recyclable polymers with desirable properties is a long-standing but challenging goal in polymer science. Central to this challenge is the need for reversible chemical reactions that can equilibrate at rapid rates and provide efficient polymerization and depolymerization cycles. Based on the dynamic chemistry of nucleophilic aromatic substitution (SNAr), we report a chemically recyclable polythioether system derived from readily accessible benzothiocane (BT) monomers. This system represents the first example of a well-defined monomer platform capable of chain-growth ring-opening polymerization through an SNAr manifold. The polymerizations reach completion in minutes, and the pendant functionalities are easily customized to tune material properties or render the polymers amenable to further functionalization. The resulting polythioether materials exhibit comparable performance to commercial thermoplastics and can be depolymerized to the original monomers in high yields.

| S-EPMC10311534 | biostudies-literature

Total synthesis of lepadiformine alkaloids using N-Boc α-amino nitriles as trianion synthons.

Project description:Lepadiformine A, B, and C were synthesized in an enantiomerically pure form using a reductive cyclization strategy. N-Boc α-amino nitriles were deprotonated and alkylated with enantiomerically pure dibromides to afford the first ring. The products were manipulated to introduce phosphate leaving groups, and subsequent reductive lithiation followed by intramolecular alkylation formed the second ring with high stereoselectivity. The third ring was formed by intramolecular displacement of a mesylate by the deprotected amine. Lepadiformine A and B contain a hydroxymethyl group adjacent to the amine. This appendage was introduced in a sequence using a Polonovski-Potier reaction as the key step. The synthetic strategy is stereoselective and convergent and demonstrates the utility of N-Boc α-amino nitriles as linchpins for alkaloid synthesis.

| S-EPMC3321086 | biostudies-literature

A strategy for the total synthesis of dragmacidin E. Construction of the core ring system.

Project description:[reaction: see text] The construction of the dragmacidin core ring system by a route that features the application of a new indole annelation reaction sequence is described.

| S-EPMC2547343 | biostudies-literature

Bioinspired Total Synthesis of Pyritide A2 through Pyridine Ring Synthesis.

Project description:Pyritides belong to the ribosomally synthesized and post-translationally modified peptide class of natural products that were recently genome-predicted and are structurally defined by unique pyridine-containing macrocycles. Inspired by their biosynthesis, proceeding through peptide modification and cycloaddition to form the heterocyclic core, we report the chemical synthesis of pyritide A2 involving pyridine ring synthesis from an amino acid precursor through aza-Diels-Alder reaction. This strategy permitted the preparation of the decorated pyridine core with an appended amino acid residue in two steps from a commercially available arginine derivative and secured pyritide A2 in ten steps. Moreover, the synthetic logic enables efficient preparation of different pyridine subunits associated with pyritides, allowing rapid and convergent access to this new class of natural products and analogues thereof.

| S-EPMC9827874 | biostudies-literature

D-Glucosamine-derived synthons for assembly of L-threo-sphingoid bases. Total synthesis of rhizochalinin C.

Project description:A five-step transformation of D-glucosamine, commencing with indium-mediated Barbier reaction without isolation of intermediates, into (R,R)-2-aminohex-5-ene-1,3-diol in 45-51% is described. The latter is a useful synthon for assembly of L-threo-sphingoid bases: long-chain aminoalkanols and aminoalkanediols with configurations antipodal to that found in mammalian D-erythro-sphingosine but prevalent among invertebrate-derived sphingolipids. The utility of the method is demonstrated by the first total synthesis of rhizochalinin C, the long-chain, "two-headed" sphingoid base aglycon of the natural product rhizochalin C from the marine sponge Rhizochalina incrustata.

| S-EPMC3548972 | biostudies-literature

Ring-Expansion Approaches for the Total Synthesis of Salimabromide.

Project description:We describe the evolution of a synthetic strategy for the construction of the marine polyketide salimabromide. Combining a bicyclo[3.1.0]hexan-2-one ring-expansion to build up a functionalized naphthalene and an unprecedented rearrangement/cyclization cascade, enabled synthesis of a dearomatized tricyclic subunit of the target compound. Alternatively, an intramolecular ketiminium [2+2]-cycloaddition and subsequent Baeyer-Villiger ring-expansion gave access to the sterically encumbered architecture of salimabromide. Sequential oxidation of the carbon framework finally enabled the total synthesis of this unusual natural product.

| S-EPMC6544523 | 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