A Palladium-Catalysed Allylic Alkylation Cascade: Towards the Total Synthesis of Thromboxanes A₂ and B₂

<p>The design and development of new chemical reactions is crucial to the ongoing success of organic synthesis research. In this work the scope and utility of a recently discovered regioselective palladium-catalysed allylic alkylation (Pd-AA) cascade was explored through increasing the range of non-symmetric pyran-based biselectrophiles and β-dicarbonyl bis-nucleophiles that can be used in this reaction. Four differentially protected tri-substituted dihydropyrans based on glucose were synthesised, including 2,3-unsaturated silyl glycosides and α,β-unsaturated lactones. These substrates were assessed as bis-electrophiles in the Pd-AA cascade. One silyl glycoside bis-electrophile, possessing a carbonate leaving group, was shown to be an excellent substrate for reaction with a number of cyclic bis-nucleophiles. Furthermore, a series of regioisomeric methylated 4-hydroxycoumarins were synthesised, tested and found to be equally effective as bis-nucleophiles in the Pd-AA cascade with both acyclic and cyclic bis-electrophiles. Advances made during this research include a novel Ferrier reaction with silanol nucleophiles, which was found to produce silyl glycosides, albeit in low yields. Additionally, several Perlin aldehydes were generated by the Ferrier-type hydrolysis of 3,4,6-tri-O-acetyl-D-glucal and led to the discovery of discrepant structural assignments in the literature. Furthermore, a ¹³C NMR shielding template was generated as a tool for the stereochemical assignment of tri-substituted dihydropyrans. An extended variant of the Pd-AA cascade was achieved by employment of the bisnucleophile Meldrum’s acid with the optimal tri-substituted bis-electrophile in the presence of H₂O. The reaction afforded a γ-butyrolactone that could serve as a potential intermediate en route to the synthesis of the biologically interesting compounds thromboxanes A₂ and B₂. This extended Pd-AA cascade, although currently unoptimised, is capable of performing five synthetic transformations in one-pot and holds the potential to improve on the current syntheses of the thromboxanes.</p>

A Palladium-Catalysed Allylic Alkylation Cascade: Towards the Total Synthesis of Thromboxanes A₂ and B₂

<p>The design and development of new chemical reactions is crucial to the ongoing success of organic synthesis research. In this work the scope and utility of a recently discovered regioselective palladium-catalysed allylic alkylation (Pd-AA) cascade was explored through increasing the range of non-symmetric pyran-based biselectrophiles and β-dicarbonyl bis-nucleophiles that can be used in this reaction. Four differentially protected tri-substituted dihydropyrans based on glucose were synthesised, including 2,3-unsaturated silyl glycosides and α,β-unsaturated lactones. These substrates were assessed as bis-electrophiles in the Pd-AA cascade. One silyl glycoside bis-electrophile, possessing a carbonate leaving group, was shown to be an excellent substrate for reaction with a number of cyclic bis-nucleophiles. Furthermore, a series of regioisomeric methylated 4-hydroxycoumarins were synthesised, tested and found to be equally effective as bis-nucleophiles in the Pd-AA cascade with both acyclic and cyclic bis-electrophiles. Advances made during this research include a novel Ferrier reaction with silanol nucleophiles, which was found to produce silyl glycosides, albeit in low yields. Additionally, several Perlin aldehydes were generated by the Ferrier-type hydrolysis of 3,4,6-tri-O-acetyl-D-glucal and led to the discovery of discrepant structural assignments in the literature. Furthermore, a ¹³C NMR shielding template was generated as a tool for the stereochemical assignment of tri-substituted dihydropyrans. An extended variant of the Pd-AA cascade was achieved by employment of the bisnucleophile Meldrum’s acid with the optimal tri-substituted bis-electrophile in the presence of H₂O. The reaction afforded a γ-butyrolactone that could serve as a potential intermediate en route to the synthesis of the biologically interesting compounds thromboxanes A₂ and B₂. This extended Pd-AA cascade, although currently unoptimised, is capable of performing five synthetic transformations in one-pot and holds the potential to improve on the current syntheses of the thromboxanes.</p>

Chemical Diversity of Volatile Macrocylic Lactones from Frogs

For a long time, frogs were believed to communicate primarily via the acoustic channel, but during the last decades it became obvious that various lineages also use chemical communication. In this Account we present our research on the identification of volatile lactones from Madagascan Mantellidae and African Hyperoliidae frogs. Both possess male specific glands that can disseminate a range of volatile compounds. Key constituents are macrocyclic lactones. They show high variability in structure and occurrence. We focus here on the synthetic approaches we have used to clarify constitution and configuration of the glandular compounds. Key synthetic methods are ring-closing metathesis and nucleophilic epoxide opening. Often, but not always, the natural compounds occurs in amounts that excludes their investigation by NMR spectroscopy. Instead, we use GC/MS analysis, GC/IR, microreactions, and synthesis to identify such components. Several aspects of our work will be described giving some insight in our scientific approach.1 Introduction2 Macrocylic Lactones from the Fatty Acid Biosynthetic Pathway3 Unsaturated Lactones4 Terpenoid Lactones5 Macrolide Occurrence6 Conclusions

Electrophilic reactivities of cyclic enones and α,β-unsaturated lactones

Different reactivity trends for cyclic and acyclic Michael acceptors were found within the framework of Mayr's experimental reactivity scales and analyzed through quantum-chemical studies.

Study of Antioxidant and Membrane Resistant Peculiarities of a New Cyan Containing Lactone in Membranes of Hepatocytes with Sarcoma-45

The antioxidant and membrane resistant peculiarities of a new derivative (2-cyan-3,4,4-trymethil-2-buten-4-olyd - CTBO) of cyan containing unsaturated lactones have been studied in membranes of hepatocytes with Sarcoma-45 1. The results of our previous research 1, 2, 3 showed significant changes of phospholipid (PL) exchange in hepatocytes of microsomal membranes at experimental animals vaccinated with Sarcoma-45 tumor strain. It is manifested in significant changes of quantitative and qualitative contents of membrane phospholipids separate fractions, increase of cytotoxic lysophospholipids (LPCs), phosphatidylinositol (PI) and phosphatidic acid (PA) levels, significant decrease of phosphatitylcholines (PC) and sphingomyeline (SP) contents, statistically significant changes of PL/PL ratio, peroxidation ratio intensity, dramatic increase of phospholipase A2 (PLA2)activity, quantitative and qualitative changes of adenyl nucleotides, as well as disorders of adenosine triphosphatase (ATPase) system activity 3, 4, 5, 6, 7.

Pleurotus ostreatus as a Biocatalyst to Obtain Bicyclic Hydroxylactones with Three or Four Methyl Groups

The purpose of the study was to explore microbial transformations in cultures of basidiomycetes Pleurotus ostreatus, two bicyclic unsaturated lactones occurring in the form of two diastereoisomers. Some of these strains were able to transform unsaturated lactones into four known and three new derivatives. The structures of all lactones were established on the basis of spectroscopic data. Both substrates and products caused a complete inhibition of growth of A. alternata and F. linii strains.