Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Application of diazene-directed fragment assembly to the total synthesis and stereochemical assignment of (+)-desmethyl-meso-chimonanthine and related heterodimeric alkaloids.

ABSTRACT: We describe the first application of our methodology for heterodimerization via diazene fragmentation towards the total synthesis of (-)-calycanthidine, meso-chimonanthine, and (+)-desmethyl-meso-chimonanthine. Our syntheses of these alkaloids feature an improved route to C3a-aminocyclotryptamines, an enhanced method for sulfamide synthesis and oxidation, in addition to a late-stage diversification leading to the first enantioselective total synthesis of (+)-desmethyl-meso-chimonanthine and its unambiguous stereochemical assignment. This versatile strategy for directed assembly of heterodimeric cyclotryptamine alkaloids has broad implications for the controlled synthesis of higher order derivatives with related substructures.

SUBMITTER: Lathrop SP

PROVIDER: S-EPMC3881597 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Application of diazene-directed fragment assembly to the total synthesis and stereochemical assignment of (+)-desmethyl-meso-chimonanthine and related heterodimeric alkaloids.

Lathrop Stephen P SP Movassaghi Mohammad M

Chemical science 20140101 1

We describe the first application of our methodology for heterodimerization via diazene fragmentation towards the total synthesis of (-)-calycanthidine, meso-chimonanthine, and (+)-desmethyl-meso-chimonanthine. Our syntheses of these alkaloids feature an improved route to C3a-aminocyclotryptamines, an enhanced method for sulfamide synthesis and oxidation, in addition to a late-stage diversification leading to the first enantioselective total synthesis of (+)-desmethyl-meso-c ...[more]

PMID: 24409339

Similar Datasets

Total Synthesis and Stereochemical Assignment of Streptide.

Project description:Streptide (1) is a peptide-derived macrocyclic natural product that has attracted considerable attention since its discovery in 2015. It contains an unprecedented post-translational modification that intramolecularly links the β-carbon (C3) of a residue 2 lysine with the C7 of a residue 6 tryptophan, thereby forming a 20-membered cyclic peptide. Herein, we report the first total synthesis of streptide that confirms the regiochemistry of the lysine-tryptophan cross-link and provides an unambiguous assignment of the stereochemistry (3R vs 3S) of the lysine-2 C3 center. Both the 3R and the originally assigned 3S lysine diastereomers were independently prepared by total synthesis, and it is the former, not the latter, that was found to correlate with the natural product. The approach enlists a powerful Pd(0)-mediated indole annulation for the key macrocyclization of the complex core peptide, utilizes an underdeveloped class of hypervalent iodine(III) aryl substrates in a palladium-catalyzed C-H activation/β-arylation reaction conducted on a lysine derivative, and provides access to material with which the role of streptide and related natural products may be examined.

| S-EPMC6821584 | biostudies-literature

Total Synthesis and Stereochemical Assignment of Nostosin B.

Project description:Nostosins A and B were isolated from a hydrophilic extract of Nostoc sp. strain from Iran, which exhibits excellent tryps inhibitory activity. Nostosin A was the most potent natural tripeptide aldehyde as trypsin inhibitor up to now. Both R- and S-2-hydroxy-4-(4-hydroxy-phenyl) butanoic acid (Hhpba) were prepared and incorporated into the total synthesis of nostosin B, respectively. Careful comparison of the NMR spectra and optical rotation data of synthetic nostosin B (1a and 1b) with the natural product led to the unambiguous identification of the R-configuration of the Hhpba fragment, which was further confirmed by co-injection with the authentic sample on HPLC using both reversed phase column and the chiral AD-RH column.

| S-EPMC5367015 | biostudies-literature

Total synthesis and stereochemical assignment of (±)-sorbiterrin A.

Project description:A concise, biomimetic approach to sorbiterrin A has been developed employing consecutive Michael additions of a 4-hydroxypyrone to a sorbicillinol derivative and silver nanoparticle-mediated bridged aldol/dehydration to construct the [3.3.1] ring system. The relative stereochemistry of sorbiterrin A was unambiguously confirmed by X-ray crystallographic analysis.

| S-EPMC3978410 | biostudies-literature

Total synthesis and stereochemical assignment of (-)-ushikulide A.

Project description:We report the determination of the full stereostructure of (-)-ushikulide A (1), a spiroketal containing macrolide by total synthesis. Ushikulide A (1) was isolated from a culture broth of Streptomyces sp. IUK-102 and exhibits potent immunosuppressant activity (IC(50) = 70 nM). To embark upon an ushikulide A synthesis, a tentative assignment was made based on analogy to cytovaricin (2), a related macrolide isolated from a culture of Streptomyces diastatochromogenes whose full structure was previously established via synthesis and X-ray crystallography. This report delineates studies on several key steps, namely a direct aldol reaction catalyzed by the dinuclear zinc ProPhenol complex, a metal catalyzed spiroketalization, as well as application of an unprecedented asymmetric alkynylation of a simple saturated aldehyde with methyl propiolate to prepare the nucleophilic partner for a Marshall-Tamaru propargylation. These studies culminated in the first total synthesis and stereochemical assignment of (-)-ushikulide A and significantly extended the scope of the above-mentioned methodologies.

| S-EPMC2791109 | biostudies-literature

Total synthesis and absolute stereochemical assignment of kibdelone C.

Project description:Kibdelones are hexacyclic tetrahydroxanthones and potent anticancer agents isolated from an Australian microbe. Herein, we describe the synthesis of a chiral, nonracemic iodocyclohexene carboxylate EF ring fragment of the kibdelones employing an intramolecular iodo halo-Michael aldol reaction and its merger with an ABCD ring fragment to afford the congener kibdelone C.

| S-EPMC3134420 | biostudies-literature

Total synthesis, stereochemical assignment, and biological activity of all known (-)-trigonoliimines.

Project description:A full account of our concise and enantioselective total syntheses of all known (-)-trigonoliimine alkaloids is described. Our retrobiosynthetic analysis of these natural products enabled identification of a single bistryptamine precursor as a precursor to all known trigonoliimines through a sequence of transformations involving asymmetric oxidation and reorganization. Our enantioselective syntheses of these alkaloids enabled the revision of the absolute stereochemistry of (-)-trigonoliimines A, B, and C. We report that trigonoliimines A, B, C and structurally related compounds showed weak anticancer activities against HeLa and U-937 cells.

| S-EPMC3947030 | biostudies-literature

Total Synthesis, Stereochemical Assignment, and Divergent Enantioselective Enzymatic Recognition of Larreatricin.

Project description:A concise and efficient total synthesis of the lignan natural product larreatricin as well as an unambiguous assignment of configuration of its enantiomers are reported, resolving a long-held controversy. Enzyme kinetic studies revealed that different polyphenol oxidases show high and remarkably divergent enantioselective recognition of this secondary metabolite.

| S-EPMC6220842 | biostudies-literature

Stereochemical assignment of intermediates in the rifamycin biosynthetic pathway by precursor-directed biosynthesis.

Project description:Natural and semisynthetic rifamycins are clinically important inhibitors of bacterial DNA-dependent RNA polymerase. Although the polyketide-nonribosomal peptide origin of the naphthalene core of rifamycin B is well established, the absolute and relative configuration of both stereocenters introduced by the first polyketide synthase module is obscured by aromatization of the naphthalene ring. To decode the stereochemistry of the rifamycin polyketide precursor, we synthesized all four diastereomers of the biosynthetic substrate for module 2 of the rifamycin synthetase in the form of their N-acetylcysteamine (SNAC) thioester. Only one diastereomer was turned over in vivo into rifamycin B, thus establishing the absolute and relative configuration of the native biosynthetic intermediates.

| S-EPMC1360739 | biostudies-literature

Stereochemical assignment of the protein-protein interaction inhibitor JBIR-22 by total synthesis.

Project description:Recent reports have highlighted the biological activity associated with a subfamily of the tetramic acid class of natural products. Despite the fact that members of this subfamily act as protein-protein interaction inhibitors that are of relevance to proteasome assembly, no synthetic work has been reported. This may be due to the fact that this subfamily contains an unnatural 4,4-disubstitued glutamic acid, the synthesis of which provides a key challenge. A highly stereoselective route to a masked form of this unnatural amino acid now enabled the synthesis of two of the possible diastereomers of JBIR-22 and allowed the assignment of its relative and absolute stereochemistry.

| S-EPMC4441253 | biostudies-literature

Stereochemical Assignment of the Protein-Protein Interaction Inhibitor JBIR-22 by Total Synthesis.

| S-EPMC4780591 | biostudies-literature