Total synthesis of isofregenedadiol
Suresh E Kurhade1, Abbas I Sanchawala, Velayutham Ravikumar
1Discovery Chemistry, Advinus Therapeutics Ltd., Quantum Towers, Plot No. 9, Rajiv Gandhi Infotech Park, Phase-I, Hinjewadi, Pune, 411057, India.
Organic Letters
|June 25, 2011
Summary
Researchers report the first total synthesis of the bicyclic diterpene isofregenedadiol. A novel one-pot reaction sequence efficiently constructed the complex molecular skeleton from a chiral starting material.
Area of Science:
- Organic Chemistry
- Natural Product Synthesis
- Medicinal Chemistry
Background:
- Isofregenedadiol is a bicyclic diterpenoid isolated from *H. viscosum*.
- Diterpenoids are a class of natural products with diverse biological activities.
- The total synthesis of complex natural products is crucial for structure confirmation and analog development.
Purpose of the Study:
- To achieve the first total synthesis of isofregenedadiol.
- To develop an efficient synthetic route utilizing a chiral pool starting material.
- To showcase a novel one-pot quadruple reaction sequence for skeleton construction.
Main Methods:
- Utilized D-(-)-pantolactone as a chiral starting material.
- Developed a one-pot reaction sequence involving enyne ring-closing metathesis/cross-metathesis/Diels-Alder/aromatization.
- Employed advanced organic synthesis techniques for multi-step transformations.
Main Results:
- Successfully synthesized isofregenedadiol, confirming its structure.
- Demonstrated the efficiency of the one-pot quadruple reaction sequence in constructing the bicyclic diterpene skeleton.
- Achieved the first total synthesis of this natural product.
Conclusions:
- The reported synthesis provides a viable route to isofregenedadiol.
- The novel one-pot reaction strategy offers a powerful tool for constructing complex polycyclic systems.
- This work contributes to the field of natural product synthesis and may facilitate further biological studies.
Related Concept Videos
01:29Biosynthesis of Lipids
Microbial membranes exhibit remarkable diversity in lipid composition, reflecting evolutionary adaptations to various environmental conditions. The three domains of life—Bacteria, Archaea, and Eukarya—synthesize membrane lipids through distinct biosynthetic pathways, leading to fundamental structural differences that impact membrane stability, function, and adaptability.Fatty Acid-Based Lipids in Bacteria and EukaryaBacteria and eukaryotes share a common fatty acid biosynthesis pathway, which...
01:57Preparation of Diols and Pinacol Rearrangement
Compounds bearing two hydroxyl groups are known as diols. When the hydroxyl groups are located on adjacent carbon atoms, the diols are called vicinal diols or glycols. Under acidic conditions, vicinal diols undergo a specific reaction called pinacol rearrangement.
The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.
The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.
01:33Regioselective Formation of Enolates
As depicted in the figure below, the unsymmetrical ketones can form two possible enolates: less substituted or more substituted enolates. Usually, the thermodynamic enolates are formed from the more substituted α-carbon atom, while the kinetic enolates are formed faster by deprotonation from the less substituted position. The thermodynamic enolates have lower energy, so they are more stable. But the energy required to form kinetic enolates is less.
01:25Insulin: Biosynthesis, Chemistry, and Preparation
The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...
01:28Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
The Diels–Alder reaction is one of the robust methods for synthesizing unsaturated six-membered rings. The reaction involves a concerted cyclic movement of six π electrons: four π electrons from the diene and two π electrons from the dienophile.
02:32Stereoisomers
On the basis of mirror symmetry, stereoisomers of an organic molecule can be further classified into diastereomers and enantiomers. Diastereomers are stereoisomers that are not mirror images of each other. Substituted alkenes, such as the cis and trans isomers of 2-butene, are diastereomers, as these molecules exhibit different spatial orientations of their constituent atoms, are not mirror images of each other, and do not interconvert. Here, the interconversion is suppressed due to restricted...