Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis of the bis(cyclohexenone) core of (-)-lomaiviticin A.

ABSTRACT: (-)-Lomaiviticin A is a complex C ₂-symmetric bacterial metabolite comprising two diazotetrahydrobenzo[b]fluorene (diazofluorene) residues and four 2,6-dideoxy glycosides, α-l-oleandrose and N,N-dimethyl-β-l-pyrrolosamine. The two halves of lomaiviticin A are linked by a single carbon-carbon bond oriented syn with respect to the oleandrose residues. While many advances toward the synthesis of lomaiviticin A have been reported, including synthesis of the aglycon, a route to the bis(cyclohexenone) core bearing any of the carbohydrate residues has not been disclosed. Here we describe a short route to a core structure of lomaiviticin A bearing two α-l-oleandrose residues. The synthetic route features a Stille coupling to form the conjoining carbon-carbon bond of the target and a double reductive transposition to establish the correct stereochemistry at this bond. Two synthetic routes were developed to elaborate the reductive transposition product to the bis(cyclohexenone) target. The more efficient pathway features an interrupted Barton vinyl iodide synthesis followed by oxidative elimination of iodide to efficiently establish the enone functionalities in the target. The bis(cyclohexenone) product may find use in a synthesis of lomaiviticin A itself.

SUBMITTER: Rose JA

PROVIDER: S-EPMC8159427 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Synthesis of functionalized cyclohexenone core of welwitindolinones via rhodium-catalyzed [5 + 1] cycloaddition.

Project description:The cyclohexenone core of welwitindolinones was synthesized by a Rh(I)-catalyzed [5 + 1]-cycloaddition of an allenylcyclopropane with CO. A pentasubstituted cyclopropane was prepared successfully by a Rh(II)-catalyzed intramolecular cyclopropanation of alkenes with chlorodiazoacetates.

| S-EPMC3480994 | biostudies-literature

11-Step enantioselective synthesis of (-)-lomaiviticin aglycon.

Project description:Lomaiviticins A and B are complex antitumor antibiotics that were isolated from a strain of Micromonospora. A confluence of several unusual structural features renders the lomaiviticins exceedingly challenging targets for chemical synthesis. We report an 11-step, enantioselective synthetic route to lomaiviticin aglycon. Our route proceeds by late-stage, stereoselective dimerization of two equivalent monomeric intermediates, a transformation that may share parallels with the natural products' biosyntheses. The route we describe is scalable and convergent, and it lays the foundation for determination of the mode of action of these natural products.

| S-EPMC5357143 | biostudies-literature

Synthesis of the bis-tetrahydropyran core of amphidinol 3.

Project description:A convergent synthesis of the C31-C52 bis-tetrahydropyran core of the natural product amphidinol 3 is reported. A common intermediate was synthesized from d-tartaric acid utilizing an asymmetric glycolate alkylation/ring-closing metathesis sequence to construct the THP rings. Differential elaboration of the common intermediate allowed the synthesis of two distinct coupling partners which were joined through a modified Horner-Wadsworth-Emmons olefination to provide the bis-tetrahydropyran core.

| S-EPMC2929927 | biostudies-literature

Improved Synthesis of and Nucleophilic Addition to 2-Formyl-2-Cyclohexenone.

Project description:A preparation of 2-formyl-2-cyclohexenone in nearly quantitative yield and purity of approximately 95% is described. It is scalable and has been extended to the synthesis of the 5- and 7-membered ring homologs with comparable yields. Conditions have also been developed for the successful conjugate addition of dimethylmalonate to 2-formyl-2-cyclohexenone, in good and scalable yield (60%). This result has been extended to 5 other nucleophile classes, and the dimethylmalonate conjugate addition has been demonstrated with 2-formyl-2-cyclopentenone and 2-formyl-2-cycloheptenone.

| S-EPMC4290381 | biostudies-literature

Synthesis and Biological Evaluation of (2<i>S</i>,2'<i>S</i>)-Lomaiviticin A.

Project description:(-)-Lomaiviticin A (1) is a genotoxic C2-symmetric metabolite that arises from the formal dimerization of two bis(glycosylated) diazotetrahydrobenzo[b]fluorenes. Here we present a synthesis of the monomer 17 and its coupling to form (2S,2'S)-lomaiviticin A (4), an unnatural diastereomer of 1. (2S,2'S)-Lomaiviticin A (4) is significantly less genotoxic, a result we attribute to changes in the orientation of the diazofluorene and carbohydrate residues, relative to 1. These data bring the importance of the configuration of the conjoining bond to light and place the total synthesis of 1 itself within reach.

| S-EPMC8174553 | biostudies-literature

Synthesis of highly functionalized cyclohexenone rings: rhodium-catalyzed 1,3-acyloxy migration and subsequent [5+1] cycloaddition.

Project description: Not available

| S-EPMC3131693 | biostudies-literature

Synthesis and application of a novel bis-1,2,3-triazole ligand containing a 2,2'-bipyrrolidine core.

Project description:Herein, we describe the synthesis of a novel bis-1,2,3-triazole ligand which contains an internal N-alkylated 2,2'-bipyrrolidine linker. By using simple starting materials, the ligand could be generated in good yield through several synthetic steps. To investigate the potential for the application of this ligand in transition metal catalysis, we generated a bis-Au(I) complex in nearly quantitative yield and examined its reactivity in the context of alkyne hydration. Both alkyl and aryl terminal alkynes could be efficiently converted to their corresponding ketones in nearly quantitative yields with only 1% catalyst loading under mild conditions.

| S-EPMC6867125 | biostudies-literature

Mechanism of Nucleophilic Activation of (-)-Lomaiviticin A.

Project description:(-)-Lomaiviticin A (1) is a C2-symmetric cytotoxin that contains two diazofluorene functional groups and which induces double-strand breaks (DSBs) in DNA. Evidence suggests DNA cleavage is initiated by hydrogen atom abstraction from the deoxyribose backbone. Here we demonstrate the formation of the vinyl radicals 1· and 2· from 1 by 1,7-addition of thiols to the diazofluorenes. These radicals can affect hydrogen atom abstraction from methanol and acetone. The first addition of thiol to 1 proceeds at a much greater rate than the second. The diazosulfide 5 formed en route to 1· has been detected at -50 °C and undergoes decomposition to 1· with a half-life of 110 min at -20 °C under air. These data, which constitute the first direct evidence for the generation of 1· and 2· from 1, provide insights into the mechanism of DNA cleavage by 1.

| S-EPMC5339879 | biostudies-literature

Total Synthesis of Calothrixins A and B via Oxidative Radical Reaction of Cyclohexenone with Aminophenanthridinedione.

Project description:Bioactive indolo[3,2-j]phenanthridine alkaloids, calothrixin B and its N-oxide derivative calothrixin A have been synthesized via an oxidative free radical reaction. calothrixin B is generated from the commercially available 2,4,5-trimethoxybenzaldehyde in only 7 steps. The key step in this synthesis is the Mn(OAc)3 mediated oxidative free radical reaction of 9-(benzylamino)phenanthridine -7,10-dione with cyclohexenone to form 12-benzyl-12H-indolo[3,2-j]phenanthridine-7,13-dione.

| S-EPMC4313744 | biostudies-other

Enantioselective synthesis of the lomaiviticin aglycon full carbon skeleton reveals remarkable remote substituent effects during the dimerization event.

Project description: Not available

| S-EPMC3152949 | biostudies-literature