Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Towards the Total Synthesis of Pl-3: Preparation of the Eastern Fragment through a Diastereoselective SmI₂-Mediated Reformatsky Reaction.

ABSTRACT: The jatrophane diterpene Pl-3, isolated in 2003 from Euphorbia platyphyllos, is a structurally complex natural product with highly promising biological properties that include pronounced antiproliferative activity and the inhibition of the efflux-pump activity of multidrug resistance p-glycoprotein. Herein, the synthesis of the eastern fragment of Pl-3 is outlined. The target compound is synthesized in nine synthetic operations in good overall yield, starting from readily available d-ribose. The key step in the preparation of the eastern part of Pl-3 is a diastereoselective SmI₂-mediated Reformatsky reaction. The proposed route is highly flexible and could also be applied to the synthesis of structurally related jatrophane diterpenes.

SUBMITTER: Furst R

PROVIDER: S-EPMC3654569 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Towards the Total Synthesis of Pl-3: Preparation of the Eastern Fragment through a Diastereoselective SmI2-Mediated Reformatsky Reaction.

Fürst Rita R Lentsch Christoph C Rinner Uwe U

European journal of organic chemistry 20130307 12

The jatrophane diterpene Pl-3, isolated in 2003 from Euphorbia platyphyllos, is a structurally complex natural product with highly promising biological properties that include pronounced antiproliferative activity and the inhibition of the efflux-pump activity of multidrug resistance p-glycoprotein. Herein, the synthesis of the eastern fragment of Pl-3 is outlined. The target compound is synthesized in nine synthetic operations in good overall yield, starting from readily available d-ribo ...[more]

PMID: 23687456

Similar Datasets

Diastereoselective Radical 1,4-Ester Migration: Radical Cyclizations of Acyclic Esters with SmI2.

Project description:Reductive cyclizations of carbonyl compounds, mediated by samarium(II) diiodide (SmI2, Kagan's reagent), represent an invaluable platform to generate molecular complexity in a stereocontrolled manner. In addition to classical ketone and aldehyde substrates, recent advances in radical chemistry allow the cyclization of lactone and lactam-type substrates using SmI2. In contrast, acyclic esters are considered to be unreactive to SmI2 and their participation in reductive cyclizations is unprecedented. Here, we report a diastereoselective radical 1,4-ester migration process, mediated by SmI2, that delivers stereodefined alkene hydrocarboxylation products via radical cyclization of acyclic ester groups in α-carbomethoxy δ-lactones. Isotopic labeling experiments and computational studies have been used to probe the mechanism of the migration. We propose that a switch in conformation redirects single electron transfer from SmI2 to the acyclic ester group, rather than the "more reactive" lactone carbonyl. Our study paves the way for the use of elusive ketyl radicals, derived from acyclic esters, in SmI2-mediated reductive cyclizations.

| S-EPMC9377304 | biostudies-literature

Towards sub-millisecond cryo-EM grid preparation.

Project description:Sample preparation is still a significant problem for many single particle cryo-EM workflows and our understanding and developments in the area lag behind that of image processing and microscope design. Over the last few years there has been growing evidence that many of the problems which occur during sample preparation are during the time the sample resides within the thin film created during the conventional blotting process. In parallel, faster grid preparation approaches have been developed for time-resolved cryo-EM experiments allowing for non-equilibrium intermediates to be captured on the ms timescale. Therefore, an important question is how fast can we prepare suitable grids for imaging by cryo-EM and how much does this mitigate the problems observed in sample preparation? Here we use a novel approach which has been developed for time-resolved studies to produce grids on an estimated sub-1 ms timescale. While the method comes with its own challenges, a 3.8 Å reconstruction of apoferritin prepared with the ultrafast method shows that good resolutions can be achieved. Although several orders of magnitude faster than conventional approaches we show using a ribosome sample, that interactions with the air-water interface cannot be avoided with preferred orientations still present. Therefore, the work shows that faster reactions can be captured but poses the question whether speed is the answer to problems with sample preparation.

| S-EPMC9642037 | biostudies-literature

Diastereoselective synthesis of pentasubstituted gamma-butyrolactones from silyl glyoxylates and ketones through a double Reformatsky reaction.

Project description:Three contiguous stereocenters can be established with remarkable diastereoselectivity in a double Reformatsky sequence. Densely functionalized gamma-butyrolactones were assembled rapidly by this approach, in which a ketone is used as the terminal electrophile (see scheme). Secondary transformations of the lactone products enhance their synthetic utility. R(1) = Me, H; R(2) = alkyl, aryl, CF(3); Bn = benzyl, TBS = tert-butyldimethylsilyl.

| S-EPMC2801152 | biostudies-literature

Formal total synthesis of histrionicotoxin alkaloids via Hg(OTf)2-catalyzed cycloisomerization and SmI2-induced ring expansion.

Project description:The efficient formal total synthesis of histrionicotoxin alkaloids was achieved. In this process, two key reactions were used to construct a core 1-azaspiro[5.5]undecane framework common to histrionicotoxins: a mercuric triflate (Hg(OTf)2)-catalyzed cycloisomerization of a linear substrate, which was developed in our laboratory, and a samarium iodide (SmI2)-mediated ring expansion.

| S-EPMC9079123 | biostudies-literature

Toward the Total Synthesis of Scleritodermin A: Preparation of the C(1)-N(15) Fragment.

Project description:The synthesis of the C(1)-N(15) fragment of the marine natural product Scleritodermin A has been accomplished through a short and stereocontrolled sequence. Highlights of this route include the synthesis of the novel ACT fragment and the formation of the alpha-keto amide linkage by the use of a highly activated alpha, beta-ketonitrile.

| S-EPMC1832122 | biostudies-literature

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment.

Project description:The stereoselective synthesis of the (Z)-enamide fragment of chondrochloren (1) is described. A Buchwald-type coupling between amide 3 and (Z)-bromide 4 was used to generate the required fragment. The employed amide 3 comprising three chiral centers was obtained through a seven-step sequence starting from ᴅ-ribonic acid-1,4-lactone. The (Z)-vinyl bromide 4 is accessible in four steps from 4-hydroxybenzaldehyde. The pivotal cross coupling between both fragments was achieved after extensive experimentation with copper(I) iodide, K2CO3 and N,N'-dimethylethane-1,2-diamine.

| S-EPMC7176928 | biostudies-literature

Molecular dissection of resistance gene cluster and candidate gene identification of Pl17 and Pl19 in sunflower by whole-genome resequencing.

Project description:Sunflower (Helianthus annuus L.) production is challenged by different biotic and abiotic stresses, among which downy mildew (DM) is a severe biotic stress that is detrimental to sunflower yield and quality in many sunflower-growing regions worldwide. Resistance against its infestation in sunflower is commonly regulated by single dominant genes. Pl17 and Pl19 are two broad-spectrum DM resistance genes that have been previously mapped to a gene cluster spanning a 3.2 Mb region at the upper end of sunflower chromosome 4. Using a whole-genome resequencing approach combined with a reference sequence-based chromosome walking strategy and high-density mapping populations, we narrowed down Pl17 to a 15-kb region flanked by SNP markers C4_5711524 and SPB0001. A prospective candidate gene HanXRQChr04g0095641 for Pl17 was identified, encoding a typical TNL resistance gene protein. Pl19 was delimited to a 35-kb region and was approximately 1 Mb away from Pl17, flanked by SNP markers C4_6676629 and C4_6711381. The only gene present within the delineated Pl19 locus in the reference genome, HanXRQChr04g0095951, was predicted to encode an RNA methyltransferase family protein. Six and eight SNP markers diagnostic for Pl17 and Pl19, respectively, were identified upon evaluation of 96 diverse sunflower lines, providing a very useful tool for marker-assisted selection in sunflower breeding programs.

| S-EPMC6802088 | biostudies-literature

High-Density Mapping and Candidate Gene Analysis of Pl18 and Pl20 in Sunflower by Whole-Genome Resequencing.

Project description:Downy mildew (DM) is one of the severe biotic threats to sunflower production worldwide. The inciting pathogen, Plasmopara halstedii, could overwinter in the field for years, creating a persistent threat to sunflower. The dominant genes Pl18 and Pl20 conferring resistance to known DM races have been previously mapped to 1.5 and 1.8 cM intervals on sunflower chromosomes 2 and 8, respectively. Utilizing a whole-genome resequencing strategy combined with reference sequence-based chromosome walking and high-density mapping in the present study, Pl18 was placed in a 0.7 cM interval on chromosome 2. A candidate gene HanXRQChr02g0048181 for Pl18 was identified from the XRQ reference genome and predicted to encode a protein with typical NLR domains for disease resistance. The Pl20 gene was placed in a 0.2 cM interval on chromosome 8. The putative gene with the NLR domain for Pl20, HanXRQChr08g0210051, was identified within the Pl20 interval. SNP markers closely linked to Pl18 and Pl20 were evaluated with 96 diverse sunflower lines, and a total of 13 diagnostic markers for Pl18 and four for Pl20 were identified. These markers will facilitate to transfer these new genes to elite sunflower lines and to pyramid these genes with broad-spectrum DM resistance in sunflower breeding.

| S-EPMC7765508 | biostudies-literature

Samarium iodide-mediated Reformatsky reactions for the stereoselective preparation of ?-hydroxy-?-amino acids: synthesis of isostatine and dolaisoleucine.

Project description:The synthesis of ?-hydroxy-?-amino acids via SmI(2)-mediated Reformatsky reactions of ?-chloroacetyloxazolidinones with aminoaldehydes is reported. Diastereoselective coupling is demonstrated to depend on the absolute configuration of the Evans chiral auxiliary employed in the reaction, allowing erythro or threo products to be obtained selectively. The potential utility of the methodology is exemplified by the facile synthesis of biologically relevant N-Boc-isostatine (2b) and N-Boc-dolaisoleucine (3c).

| S-EPMC3259735 | biostudies-literature

Fragment-Based Screen of SARS-CoV-2 Papain-like Protease (PLpro).

Project description:Coronaviruses have been responsible for numerous viral outbreaks in the past two decades due to the high transmission rate of this family of viruses. The deadliest outbreak is the recent Covid-19 pandemic, which resulted in over 7 million deaths worldwide. SARS-CoV-2 papain-like protease (PLPro) plays a key role in both viral replication and host immune suppression and is highly conserved across the coronavirus family, making it an ideal drug target. Herein we describe a fragment-based screen against PLPro using protein-observed NMR experiments, identifying 77 hit fragments. Analyses of NMR perturbation patterns and X-ray cocrystallized structures reveal fragments bind to two distinct regions of the protein. Importantly none of the fragments identified belong to the same chemical class as the few reported inhibitors, allowing for the discovery of a novel class of PLPro inhibitors.

| S-EPMC11318101 | biostudies-literature