Paspalinine, a tremorgenic metabolite from Stevens et Hall

Gallagher, Rex T.; Finer, Janet; Clardy, Jon; Leutwiler, Albert; Weibel, Franz R.; Acklin, W.; Arigoni, D.

doi:10.1016/s0040-4039(00)71177-4

Cited by 75 publications

(39 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To complete our synthesis, the Gassman indolization of 24 previously employed by Smith proved effective in affording paspaline ( 1 ) in 46% yield over four steps. 10a,25 In addition to matching the reported analytical data, 2a,10d an X-ray diffraction study of synthetic paspaline provided secondary confirmation of the final structure 3c and the sense of enantioinduction imposed in the biocatalytic desymmetrization. 26 …”

supporting

confidence: 57%

“…1 Among these, jervine and cyclopamine have demonstrated marked inhibition of the hedgehog signaling pathway in vitro and are currently under study in clinical trials. The structurally distinct indole diterpenoids were first discovered from Claviceps paspali in the 1960s with the isolation of paspaline ( 1 , Scheme 1); 2 related compounds including paspalinine, 3 paspalicine, 2 paxilline, 4 JBIR-03, 5 and others have since been reported. 6 Derivatives of paspalinine have shown potent activity as potassium channel antagonists and may be useful in the treatment of glaucoma.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A Global and Local Desymmetrization Approach to the Synthesis of Steroidal Alkaloids: Stereocontrolled Total Synthesis of Paspaline

Sharpe

Johnson

2015

J. Am. Chem. Soc.

View full text Add to dashboard Cite

A stereocontrolled total synthesis of the indole diterpenoid natural product paspaline is described. Key steps include a highly diastereoselective enzymatic desymmetrization, substrate-directed epoxidation, Ireland-Claisen rearrangement, and diastereotopic group selective C–H acetoxylation to assemble the target with excellent stereofidelity. The route and results described herein outline complementary conceptual disconnections in the arena of steroid natural product synthesis.

show abstract

supporting

confidence: 57%

mentioning

confidence: 99%

A Global and Local Desymmetrization Approach to the Synthesis of Steroidal Alkaloids: Stereocontrolled Total Synthesis of Paspaline

Sharpe

Johnson

2015

J. Am. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“…2 Claviceps paspali , another species in this genus, has been linked to “paspalum stagger” poisoning in livestock, 3 and it was from this fungus that Arigoni and co-workers isolated paspaline ( 1 , Figure 1) and paspalicine ( 4 ), the first of a now extensive family of indole diterpene alkaloid natural products. 4 A diverse range of related structures have since been reported including paspaline B ( 2 ), 5 paspalinine ( 3 ), 6 JBIR-03 ( 5 ), 7 and paxilline ( 6 ). 8 …”

Section: Introductionmentioning

confidence: 99%

Asymmetric Total Synthesis of the Indole Diterpene Alkaloid Paspaline

Sharpe

Johnson

2015

J. Org. Chem.

View full text Add to dashboard Cite

An enantioselective synthesis of the indole diterpenoid natural product paspaline is disclosed. Critical to this approach was the implementation of stereoselective desymmetrization reactions to assemble key stereocenters of the molecule. The design and execution of these tactics are described in detail, and a thorough analysis of observed outcomes is presented, ultimately providing the title compound in high stereopurity. This synthesis provides a novel template for preparing key stereocenters in this family of molecules, and the reactions developed en route to paspaline present a series of new synthetic disconnections in preparing steroidal natural products.

show abstract

“…However, this technique is best suited for volatile compounds (Fellows et al 1981). Although X-ray crystallography provides detailed information about the structures of organic molecules, it has only been rarely applied to study IDTs (Gallagher et al 1980a; Nozawa et al 1987; Kawai and Nozawa 1989) since it requires special pretreatments and relatively larger amounts of the sample.…”

Section: Detection and Structural Characterization Of Idts In Biologimentioning

confidence: 99%

Tremorgenic and neurotoxic paspaline-derived indole-diterpenes: biosynthetic diversity, threats and applications

Kozák

Szilágyi

Tóth

et al. 2019

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

Indole-diterpenes (IDTs) such as the aflatrems, janthitrems, lolitrems, paspalitrems, penitrems, shearinines, sulpinines, and terpendoles are biogenetically related but structurally varied tremorgenic and neurotoxic mycotoxins produced by fungi. All these metabolites derive from the biosynthetic intermediate paspaline, a frequently occurring IDT on its own right. In this comprehensive review, we highlight the similarities and differences of the IDT biosynthetic pathways that lead to the generation of the main paspaline-derived IDT subgroups. We survey the taxonomic distribution and the regulation of IDT production in various fungi and compare the organization of the known IDT biosynthetic gene clusters. A detailed assessment of the highly diverse biological activities of these mycotoxins leads us to emphasize the significant losses that paspaline-derived IDTs cause in agriculture, and compels us to warn about the various hazards they represent towards human and livestock health. Conversely, we also describe the potential utility of these versatile molecules as lead compounds for pharmaceutical drug discovery, and examine the prospects for their industrial scale manufacture in genetically manipulated IDT producers or domesticated host microorganisms in synthetic biological production systems.

show abstract

Paspalinine, a tremorgenic metabolite from Stevens et Hall

Cited by 75 publications

References 8 publications

A Global and Local Desymmetrization Approach to the Synthesis of Steroidal Alkaloids: Stereocontrolled Total Synthesis of Paspaline

A Global and Local Desymmetrization Approach to the Synthesis of Steroidal Alkaloids: Stereocontrolled Total Synthesis of Paspaline

Asymmetric Total Synthesis of the Indole Diterpene Alkaloid Paspaline

Tremorgenic and neurotoxic paspaline-derived indole-diterpenes: biosynthetic diversity, threats and applications

Contact Info

Product

Resources

About