Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A 15-step synthesis of (+)-ryanodol.

ABSTRACT: (+)-Ryanodine and (+)-ryanodol are complex diterpenoids that modulate intracellular calcium-ion release at ryanodine receptors, ion channels critical for skeletal and cardiac muscle excitation-contraction coupling and synaptic transmission. Chemical derivatization of these diterpenoids has demonstrated that certain peripheral structural modifications can alter binding affinity and selectivity among ryanodine receptor isoforms. Here, we report a short chemical synthesis of (+)-ryanodol that proceeds in only 15 steps from the commercially available terpene (S)-pulegone. The efficiency of the synthesis derives from the use of a Pauson-Khand reaction to rapidly build the carbon framework and a SeO2-mediated oxidation to install three oxygen atoms in a single step. This work highlights how strategic C-O bond constructions can streamline the synthesis of polyhydroxylated terpenes by minimizing protecting group and redox adjustments.

SUBMITTER: Chuang KV

PROVIDER: S-EPMC5505075 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A 15-step synthesis of (+)-ryanodol.

Chuang Kangway V KV Xu Chen C Reisman Sarah E SE

Science (New York, N.Y.) 20160801 6302

(+)-Ryanodine and (+)-ryanodol are complex diterpenoids that modulate intracellular calcium-ion release at ryanodine receptors, ion channels critical for skeletal and cardiac muscle excitation-contraction coupling and synaptic transmission. Chemical derivatization of these diterpenoids has demonstrated that certain peripheral structural modifications can alter binding affinity and selectivity among ryanodine receptor isoforms. Here, we report a short chemical synthesis of (+)-ryanodol that proce ...[more]

PMID: 27563092

Similar Datasets

Studies Targeting Ryanodol Result in an Annulation Reaction for the Synthesis of a Variety of Fused Carbocycles.

Project description:An annulation reaction is described to access a range of polycyclic and highly oxygenated carbocycles. First developed in an approach to the synthesis of ryanodol, metallacycle-mediated annulative diketone-alkyne coupling defines a framework for realization of new retrosynthetic relationships for complex molecule synthesis. In addition to demonstrating this reaction in the context of forging distinct carbocyclic systems, including those featuring a seven-membered ring, the choice of quenching reagent leads to unique reaction outcomes.

| S-EPMC6677624 | biostudies-literature

Toward the Total Synthesis of Ryanodol via Oxidative Alkyne-1,3-Diketone Annulation: Construction of a Ryanoid Tetracycle.

Project description:A synthetic strategy conceived with the intent of establishing a novel approach to the de novo construction of ryanoids is described that is based on a recently developed metallacycle-mediated intramolecular oxidative alkyne-1,3-diketone coupling reaction. In short, a one-pot annulation/oxidation sequence is shown to be capable of establishing a densely oxygenated polycyclic intermediate that could be converted to a composition of matter that contains the ABCD tetracyclic ring system present in the ryanoid family of natural products.

| S-EPMC6199674 | biostudies-literature

Ryanodol action on calcium sparks in ventricular myocytes.

Project description:The action of ryanodol on single cardiac ryanodine receptor (RyR2) channels in bilayers and local RyR2-mediated Ca(2+) release events (Ca(2+) sparks) in ventricular myocytes was defined. At the single-channel level, ryanodol intermittently modified single channels into a long-lived subconductance state with an average duration of 3.8 +/- 0.2 s. Unlike ryanodine, ryanodol did not change the open probability (Po) of unmodified channels, and high concentrations did not promote full-channel closure. Ryanodol action was Po dependent with the K (D) varying roughly from 20 to 80 muM as Po changed from approximately 0.2 to 1, respectively. Ryanodol preferentially bound during long channel openings. In intact and permeabilized rat myocytes, ryanodol evoked trains of sparks at active release sites resulting in a significant increase in overall spark frequency. Ryanodol did not increase the number of active release sites. Long-lived Ca(2+) release events were observed but infrequently, and ryanodol action was readily reversed upon drug washout. We propose that ryanodol modifies a few channels during a Ca(2+) spark. These modified channels mediate a sustained low-intensity Ca(2+) release that repeatedly triggers sparks at the same release site. We conclude that ryanodol is an easily generated reversible probe that can be effectively used to explore RyR2-mediated Ca(2+) release in cells.

| S-EPMC3315696 | biostudies-literature

An Oxidative Dearomatization Approach To Prepare the Pentacyclic Core of Ryanodol.

Project description:An approach to synthesize the pentacyclic framework of the polyol diterpenoid ryanodol is reported. The ABC tricycle was constructed by a Co-mediated Pauson-Khand reaction, and both radical and anionic cyclization pathways were developed to form the E-ring. In addition, a reaction sequence involving SeO2-mediated enone oxidation and hydroxyl-directed oxy-Michael addition was developed to introduce the A-ring oxidation. The feasibility of forming the bridging D-ring by an oxidative dearomatization was established.

| S-EPMC6103443 | biostudies-literature

Two-step pathway for isoprenoid synthesis.

Project description:Isoprenoids comprise a large class of chemicals of significant interest due to their diverse properties. Biological production of isoprenoids is considered to be the most efficient way for their large-scale production. Isoprenoid biosynthesis has thus far been dependent on pathways inextricably linked to glucose metabolism. These pathways suffer from inherent limitations due to their length, complex regulation, and extensive cofactor requirements. Here, we present a synthetic isoprenoid pathway that aims to overcome these limitations. This isopentenol utilization pathway (IUP) can produce isopentenyl diphosphate or dimethylallyl diphosphate, the main precursors to isoprenoid synthesis, through sequential phosphorylation of isopentenol isomers isoprenol or prenol. After identifying suitable enzymes and constructing the pathway, we attempted to probe the limits of the IUP for producing various isoprenoid downstream products. The IUP flux exceeded the capacity of almost all downstream pathways tested and was competitive with the highest isoprenoid fluxes reported.

| S-EPMC6329939 | biostudies-literature

11-Step Total Synthesis of Araiosamines.

Project description:A concise route to a small family of exotic marine alkaloids known as the araiosamines has been developed, and their absolute configuration has been assigned. The dense array of functionality, high polarity, and rich stereochemistry coupled with equilibrating topologies present an unusual challenge for chemical synthesis and an opportunity for innovation. Key steps involve the use of a new reagent for guanidine installation, a remarkably selective C-H functionalization, and a surprisingly simple final step that intersects a presumed biosynthetic intermediate. Synthetic araiosamines were shown to exhibit potency against Gram-positive and -negative bacteria despite a contrary report of no activity.

| S-EPMC5095662 | biostudies-literature

11-Step Total Synthesis of (-)-Maoecrystal V.

Project description:An expedient, practical, and enantioselective route to the highly congested ent-kaurane diterpene maoecrystal V is presented. This route, which has been several years in the making, is loosely modeled after a key pinacol shift in the proposed biosynthesis. Only 11 steps, many of which are strategic in that they build key skeletal bonds and incorporate critical functionalities, are required to access (-)-maoecrystal V. Several unique and unexpected maneuvers are featured in this potentially scalable pathway. Reevaluation of the biological activity calls into question the initial exuberance surrounding this natural product.

| S-EPMC4974602 | 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

Nine-step enantioselective total synthesis of (-)-vincorine.

Project description:A concise and highly enantioselective total synthesis of the akuammiline alkaloid (-)-vincorine has been accomplished. A key element of the synthesis is a stereoselective organocatalytic Diels-Alder, iminium cyclization cascade sequence, which serves to construct the tetracyclic alkaloid core architecture in one step from simple achiral precursors. The challenging seven-membered azepanyl ring system is installed by way of a single electron-mediated cyclization event initiated from an acyl telluride precursor. The total synthesis of (-)-vincorine is achieved in nine steps and 9% overall yield from commercially available starting materials.

| S-EPMC3667606 | biostudies-literature

One-step synthesis of carbon-supported electrocatalysts.

Project description:Cost-efficiency, durability, and reliability of catalysts, as well as their operational lifetime, are the main challenges in chemical energy conversion. Here, we present a novel, one-step approach for the synthesis of Pt/C hybrid material by plasma-enhanced chemical vapor deposition (PE-CVD). The platinum loading, degree of oxidation, and the very narrow particle size distribution are precisely adjusted in the Pt/C hybrid material due to the simultaneous deposition of platinum and carbon during the process. The as-synthesized Pt/C hybrid materials are promising electrocatalysts for use in fuel cell applications as they show significantly improved electrochemical long-term stability compared to the industrial standard HiSPEC 4000. The PE-CVD process is furthermore expected to be extendable to the general deposition of metal-containing carbon materials from other commercially available metal acetylacetonate precursors.

| S-EPMC7509379 | 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