A5074916664- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Synthetic Organic Chemistry Methods
- Chemical synthesis and alkaloids
- Asymmetric Synthesis and Catalysis
- Microbial Natural Products and Biosynthesis
- Bioactive Natural Diterpenoids Research
- Marine Sponges and Natural Products
- Nicotinic Acetylcholine Receptors Study
- Fungal Biology and Applications
- Alkaloids: synthesis and pharmacology
- Crystallography and molecular interactions
- Steroid Chemistry and Biochemistry
- Plant-based Medicinal Research
- Toxin Mechanisms and Immunotoxins
- Marine Toxins and Detection Methods
- Synthesis and Catalytic Reactions
- Plant biochemistry and biosynthesis
- Bioactive Compounds and Antitumor Agents
- Botulinum Toxin and Related Neurological Disorders
- Cholinesterase and Neurodegenerative Diseases
- Carbohydrate Chemistry and Synthesis
- Ion channel regulation and function
- Neuroendocrine regulation and behavior
- Catalytic C–H Functionalization Methods
Torrey Pines Institute For Molecular Studies
2021-2023
Scripps (United States)
2020-2023
Scripps Institution of Oceanography
2020-2023
Massachusetts Institute of Technology
2021-2022
Scripps Research Institute
2019-2021
Xi'an Jiaotong University
2014-2020
China XD Group (China)
2020
Henan University
2012-2013
The strength of the weak: An L-tert-leucine-derived amine–thiourea catalyst (see scheme, green box) promotes asymmetric vinylogous conjugate addition reaction between γ-aryl- and alkyl-substituted butenolides with butenamides enoates shown. Computational studies show preference for observed stereochemistry is a result favourable weak non-bonding interactions, which stabilize transition state.
We report a concise, stereocontrolled synthesis of the neurotoxic sesquiterpenoid (−)-picrotoxinin (1, PXN). The brevity route is due to regio- and stereoselective formation [4.3.0] bicyclic core by incorporation symmetrizing geminal dimethyl group at C5. Dimethylation then enables selective C–O bond in multiple intermediates. A series strong (C–C C–H) cleavages convert C5 gem-dimethyl C15 lactone PXN.
The asymmetric allylic alkylation of Morita-Baylis-Hillman (MBH) carbonates with allyl ketones has been developed. α-regioselective adducts, containing a hexa-1,5-diene framework important synthetic value, were achieved in up to 83% yield, >99% ee, and 50:1 dr by using commercially available Cinchona alkaloid as the catalyst. From adduct, cyclohexene bearing two adjacent chiral centers was readily prepared.
Die Stärke der Schwachen: Ein von L-tert-Leucin abgeleiteter Amin-Thioharnstoff-Katalysator (siehe Schema, grüner Kasten) vermittelt die asymmetrische vinyloge konjugierte Addition zwischen γ-Aryl- und -Alkyl-substituierten Butenoliden den gezeigten Butenamiden Enoaten. Rechnungen belegen, dass bevorzugte Stereochemie eine Folge schwachen nichtbindenden Wechselwirkungen ist, Übergangszustand stabilisieren.
An appropriately functionalized [5–7–6] tricyclic framework of tigliane and daphnane diterpenes containing seven contiguous stereocenters has been prepared in 10 steps from very simple building blocks a modular stereocontrolled fashion. The key features this approach involve an efficient visible light-induced singlet oxygen oxidative dearomatization array substrate-controlled highly diastereoselective transformations. This work provides model strategy for rapid diverted synthesis natural...
Tiglianes such as prostratin and related diterpenoids are biologically significant natural molecules long-standing targets for organic synthesis community. Due to the complex polycyclic scaffolds, high oxygenation level, dense functional groups stereocenters, their de novo chemical syntheses still face formidable challenges despite extensive efforts in past 40 years. This account details development of a modular concise prostratin, potent anti-HIV anticancer agent. The key approach this...
Abstract Minor changes to complex structures can exert major influences on synthesis strategy and functional properties. Here we explore two parallel series of picrotoxinin (PXN, 1 ) analogs identify leads with selectivity between mammalian insect ion channels. These are the first SAR studies PXN despite its >100-year history made possible by advances in total synthesis. We observe a remarkable stabilizing effect C5 methyl, which completely blocks C15 alcoholysis via destabilization an...
The common [5-7-6] tricyclic framework in tigliane and daphnane natural diterpenes containing five contiguous stereocenters has been synthesized 9 steps from readily available starting materials a completely stereocontrolled manner.
The fungal metabolite collybolide has attracted attention as a non-nitrogenous, potent, and biased agonist of the kappa-opioid receptor (KOR). Here, we report 10-step asymmetric synthesis this complex sesquiterpene that enables facile access to either enantiomer. relies on diastereoselective α-benzoyloxylation install buried C6 benzoate avoid irreversible translactonization congested, functionally dense core. Neither enantiomer, however, exhibited KOR agonism, indicating been...
The plant metabolite picrotoxinin (PXN) is a widely used tool in neuroscience for the identification of GABAergic signaling. Its hydrolysis weakly alkaline media has been observed over century and structure unstable intermediate was assigned by analogy to degradation product picrotoxic acid. Here we show this assignment be error revise spectroscopic characterization situ. Counterintuitively, occurs at lactone that remains closed major isolable product, which accounts longstanding mistake literature.
We report a concise, stereocontrolled synthesis of the neurotoxic sesquiterpenoid, (–)-picrotoxinin (<b>1</b>, PXN). The brevity route owes to regio- and stereoselective formation [4.3.0] bicyclic core by incorporation symmetrizing geminal dimethyl group at C5. A series strong C–C C–H bond oxidations convert C5 <i>gem</i>-dimethyl C15 lactone PXN. This counterintuitive strategy features first example demethylation (C–C cleavage) in total synthesis.<br>
Abstract Addition of γ‐substituted butenolides to oxazolidinone enoates in the presence chiral urea ATU affords γ,γ‐disubstituted with excellent enantioselectivity, generally as single diastereomers.