Comparative Analysis of Volatile Terpenes and Terpenoids in the Leaves of Pinus Species—A Potentially Abundant Renewable Resource

Pinaceae plants are widely distributed in the world, and the resources of pine leaves are abundant. In the extensive literature concerning Pinus species, there is much data on the composition and the content of essential oil of leaves. Still, a detailed comparative analysis of volatile terpenes and terpenoids between different species is missing. In this paper, headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry was used to determine the volatile terpenes and terpenoids of typical Pinus species in China. A total of 46 volatile terpenes and terpenoids were identified, and 12 common compounds were found, which exhibited a great diversity in the leaves of Pinus species. According to the structures and properties of the compounds, all those compounds can be classified into four categories, namely monoterpenes, oxygenated terpenes, terpene esters, and sesquiterpenes. The results of principal component analysis and cluster analysis showed that the leaves of the six Pinus species could be divided into two groups. The species and contents of volatile terpenes and terpenoids in the leaves were quite different. The results not only provide a reference for the utilization of pine leaves resource, but also bring a broader vision on the biodiversity.     

First study of rhodium(I) complexes with chiral sulfur-containing terpenoids as catalytic systems for ketone hydrosilylation

Abstract

Using a “chiral pool” approach, a number of chiral thiolate and sulfide ligands based on natural terpenes and terpenoids have been synthesized in a few simple steps. Two new Rh-thiolate complexes with the formula [Rh(CO)₂(μ-SR)]₂ were obtained. The influence of these complexes and catalytic systems formed by combining the synthesized ligands with [Rh(CO)₂(μ-Cl)]₂ and [Rh(cod)(μ-Cl)]₂, on the reaction rate, chemoselectivity, stereoselectivity and formation of tetraphenyldisiloxane in Rh-catalyzed asymmetric hydrosilylation of acetophenone as a model reaction have been studied. Mechanistic aspects of formation of silyl enol ether as a side product in the presence of S-containing ligands are presented.     

New pyrophosphate analogues: a facile access to N-(O-alkyl-sulfamoyl)phosphoramidic acids via a simple and quantitative reaction of N-(O-alkylsulfamoyl)trimethylphospha-λ-azene with bromotrimethylsilane and water

A new strategy to prepare pyrophosphate analogues through selective and quantitative cleavage of N-(O-alkylsulfamoyl)trialkylphospha-λ⁵-azene esters (R-O-SO₂-NP(OR′)₃) has been developed. Using pure bromotrimethylsilane, N-(O-alkyl-sulfamoyl)tristrimethylsilylphospha-λ⁵-azenes (R-O-SO₂-NP(OSiMe₃)₃) have been easily obtained as intermediates. N-(O-Alkyl-sulfamoyl)phosphoramidic acids (R-O-SO₂-NH-P(O)(OH)₂) have been formed quantitatively by hydrolysis of the silylated intermediates.     

Characterization and catalytic performance of methyl-grafted Ti-HMS catalysts prepared by the CVD method

Methyl-grafted Ti-HMS catalysts were prepared by the chemical vapor deposition (CVD) method using TiCl₄ as titanium source and various organic silanes as silylating agents. The catalysts were characterized by XRD, N₂-adsorption-desorption, FTIR, ²⁹Si NMR, TGA, DR UV-vis, and evaluated by the epoxidation of propylene using cumene hydroperoxide (CHP) as oxidant. The results reveal that the silylated Ti-HMS catalysts are more active than the unsilylated Ti-HMS catalyst, and the methyl-grafted Ti-HMS catalyst silylated with hexamethyldisilazane (HMDSZ) exhibits better epoxidation performance than the analogues silylated with trimethylchlorosilane (TMCS) or dimethyldichorosilane (DMDCS). It is proposed that not only the form of T-O-SiMe_n (n = 2 or 3) but also the breakage of Ti-O-T (Si-O-Si or Si-O-Ti) are observed in silylation using Cl-containing silylating agents (TMCS or DMDCS), which decrease the hydrophobicity of Ti-HMS catalysts and destroy the tetracoordinated titanium species that responsible for the epoxidation performance. This phenomenon has not been observed in silylation with HMDSZ.     

Extraction of Camphor Tree Essential Oil by Steam Distillation and Supercritical CO2 Extraction

The essential oil extracted from Cinnamomum camphora leaves is a mixture of volatile compounds, mainly terpenes, and is widely used in medicine, perfume and chemical industries. In this study, the extraction processes of essential oil from Cinnamomum camphora leaves by steam distillation and supercritical CO₂ extraction were summarized and compared, and the camphor tree essential oil was detected by GC/MS. The extraction rate of essential oil extracted by steam distillation is less than 0.5%, while that of supercritical CO₂ extraction is 4.63% at 25 MPa, 45 °C and 2.5 h. GC/MS identified 21 and 42 compounds, respectively. The content of alcohols in the essential oil is more than 35%, and that of terpenoids is more than 80%. The steam extraction method can extract volatile substances with a low boiling point and more esters and epoxides; The supercritical method is suitable for extracting weak polar substances with a high alcohol content. Supercritical CO₂ extraction can selectively extract essential oil components and effectively prevent oxidation and the escape of heat sensitive substances.     

Uncommon Terpenoids from Salvia Species: Chemistry,Biosynthesis and Biological Activities

The search for new bioactive compounds from plant sources has been and continues to be one of the most important fields of research in drug discovery. However, Natural Products research has continuously evolved, and more and more has gained a multidisciplinary character. Despite new developments of methodologies and concepts, one intriguing aspect still persists, i.e., different species belonging to the same genus can produce different secondary metabolites, whereas taxonomically different genera can produce the same compounds. The genus Salvia L. (Family Lamiaceae) comprises myriad distinct medicinal herbs used in traditional medicine worldwide that show different pharmacological activities due to the presence of a variety of interesting specialized metabolites, including mono-, sesqui-, di-, sester-, tri-, tetra-, and higher terpenoids as well as phenylpropanoids, phenolic acid derivatives, lignans, flavonoids, and alkaloids. We herein summarize the research progress on some uncommon terpenoids, isolated from members of the genus Salvia, which are well recognized for their potential pharmacological activities. This review also provides a current knowledge on the biosynthesis and occurrence of some interesting phytochemicals from Salvia species, viz. C₂₃-terpenoids, sesterterpenoids (C₂₅), dammarane triterpenoids (C₃₀), and uncommon triterpenoids (C₂₀+C₁₀). The study was carried out by searching various scientific databases, including Elsevier, ACS publications, Taylor and Francis, Wiley Online Library, MDPI, Springer, Thieme, and ProQuest. Therefore, 106 uncommon terpenoids were identified and summarized. Some of these compounds possessed a variety of pharmacological properties, such as antibacterial, antiviral, antiparasitic, cytotoxic and tubulin tyrosine ligase inhibitory activities. Due to the lack of pharmacological information for the presented compounds gathered from previous studies, biological investigation of these compounds should be reinvestigated.     

Supercritical CO2 Extract from Microalga Tetradesmus obliquus: The Effect of High-Pressure Pre-Treatment

High-pressure pre-treatment followed by supercritical carbon dioxide (ScCO₂) extraction (300 bar, 40 °C) was applied for the attainment of the lipophilic fraction of microalga Tetradesmus obliquus. The chemical profile of supercritical extracts of T. obliquus was analyzed by ultra-high-performance liquid chromatography–high-resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). Moreover, the impact of ScCO₂ on the microbiological and metal profile of the biomass was monitored. The application of the pre-treatment increased the extraction yield approximately three-fold compared to the control. In the obtained extracts (control and pre-treated extracts), the identified components belonged to triacylglyceroles, fatty acid derivatives, diacylglycerophosphocholines and diacylglycerophosphoserines, pigments, terpenes, and steroids. Triacylglycerols (65%) were the most dominant group of compounds in the control extract. The pre-treatment decreased the percentage of triacylglycerols to 2%, while the abundance of fatty acid derivatives was significantly increased (82%). In addition, the pre-treatment led to an increase in the percentages of carotenoids, terpenoids, and steroids. Furthermore, it was determined that ScCO₂ extraction reduced the number of microorganisms in the biomass. Considering its microbiological and metal profiles, the biomass after ScCO₂ can potentially be used as a safe and important source of organic compounds.     

Terpenoids from Marine Soft Coral of the Genus Xenia in 1977 to 2019

Members of the marine soft coral genus Xenia are rich in a diversity of diterpenes. A total of 199 terpenes consisting of 14 sesquiterpenes, 180 diterpenes, and 5 steroids have been reported to date. Xenicane diterpenes were reported to be the most common chemical skeleton biosynthesized by members of this genus. Most of the literature reported the chemical diversity of Xenia collected from the coral reefs in the South China Sea and the coastal waters of Taiwan. Although there was a brief review on the terpenoids of Xenia in 2015, the present review is a comprehensive overview of the structural diversity of secondary metabolites isolated from soft coral genus Xenia and their potent biological activity as reported between 1977 to 2019.     

Novel lupane triterpenoids containing allyl substituents in ring A: synthesis and in vitro study of antiinflammatory and cytotoxic properties

Selective methods for the synthesis of C(2)-monoallyl and C(2)-diallyl derivatives of lupane terpenoids were developed. The methods involve reactions of allyl halides with potassium enolates or potassium enoxy(triethyl)borates generated in situ from 3-oxolupanes (betulonic acid, 3-oxo betulin) under the action of KN(SiMe₃)₂, KH, or Bu^tOK with subsequent addition of Et₃B. The use of the reagent KN(SiMe₃)₂-Et3B in 1,2-dimethoxyethane ensured the kinetically controlled generation of enolate anions, which yielded 2??-propenyl lupane terpenoids with high stereoselectivity. Reactions of 3-oxolupanes with excesses of Bu^tOK and allyl halide (2.5 equiv.) gave 2,2-bisallylation products. In vitro studies revealed that one of the latter efficiently suppresses the NO production by activated macrophages and has an antitumor effect on Ehrlich carcinoma and P-815 mastocytoma cell lines.     

Tetrabutylammonium phenoxide induced reaction of silyl nucleophiles

Reaction of silyl dithiolanes with electrophiles can be efficiently promoted by catalytic amounts of tetrabutylammonium phenoxide (PhONn-Bu₄), leading to a convenient access to functionalized dithiolanes. PhONn-Bu₄ proved effective also in promoting reactions of silylated sulfides such as PhSTMS and HMDST as well as silylated selenides such as PhSeTMS and HMDSS toward epoxides. The present reactivity is also observed on using ILs as reaction media.     

Ferrocenyl Sulfinylimide and Diferrocenyl Sulfurdiimide,Fc?NSO and Fc(NSN)Fc

1 Abbreviations and Nomenclature: Fc = η¹-ferrocenyl, CpFe(C₅H₄-); Cp = η⁵-cyclopentadienyl, η⁵-C₅H₅. Compounds containing the —NSO group are designated as either thionylimides, sulfinylimides or N-sulfinylamines. The systematic name is imido oxo sulfuranes(IV).

The reactions of ferrocenylamine, Fc? NH₂ ( 1 ), with thionyl chloride and sulfur dichloride in hexane solution in the presence of triethylamine lead to the title compounds Fc? NSO ( 2 ) and Fc(NSN)Fc ( 3 ), respectively, 2 and 3 have also been obtained in reactions of the silylated ferrocenylamine, Fc? NH(SiMe₃) ( 1b ), with thionyl chloride. The ferrocenyl sulfinylimide 2 has been converted to sulfurdiimides such as Fc(NSN)Fc ( 3 ) and Fc(NSN)R (R = ^tBu ( 4a ), SiMe₃ ( 4b )) by reaction with the lithium derivative of silylated amines, LiN(SiMe₃)R (R = Fc, ^tBu, SiMe₃). The new ferrocenyl compounds 2–4 have been characterized by their NMR spectra, and their electrochemical behaviour has been studied. The molecular structure of Fc? NSO ( 2 ) has been determined by an X-ray structure analysis; the sulfinylimide has the Z configuration, and the —NSO group is coplanar with the cyclopentadienyl ring to which it is attached.     

Partial functionalisation of C4-symmetric tetramethoxyresorcinarenes

Investigations into the distal-functionalisation of the phenols of racemic C₄-symmetric tetramethoxyresorcinarene has led to a simple, single-step procedure that allows the isolation of gram quantities of partially silylated derivatives, with the targeted distally silylated resorcinarene being obtained in a yield of 31%. These partially silylated derivatives would serve as versatile intermediates for the selective functionalisation of this elegant architecture. The solid-state structures of many of these derivatives have been determined by single crystal X-ray crystallography.     

Novel synthetic strategy toward abietane and podocarpane-type diterpenes from (−)-sclareol: synthesis of the antitumor (+)-7-deoxynimbidiol

A new route to abietane and podocarpane-type terpenoids from labdane diterpenes is reported. The key step is the transformation of β-ketoester 9 into the corresponding O-acetylsalicylate ester 18, via a manganese(III)-based oxidative free-radical cyclization carried out in Ac₂O. Utilizing this, the synthesis of the antitumor (+)-7-deoxynimbidiol (5) from (−)-sclareol (11) has been achieved. (+)-Nimbidiol (6) and the natural terpenoid 20 have also been synthesized.     

Cacospongione A,cacospongienone A,and cacospongienone B,new C21 difuran terpenoids from the marine sponge Cacospongiascalaris SCHMIDT of the Côte d' Azur

The sponge Cacospongia scalaris (family Thorectidae), collected at the Cap de Nice (Cǒte d'Azur), is shown to contain a series of truncated, linear C₂₁ difuran terpenoids comprising the known sponge products furospongin-1 ((+)- 1 ), furospongin-2 ( 2 ), and dihydrofurospongin-2 ((?)-(E)- 3 ), besides the new products cacospongione A ((?)- 4 ), cacospongienone A ((?)-(Z)- 6 ), and cacospongienone B ((?)-(E)- 6 ), whose absolute configurations have been assigned by chemical correlations with (+)- 1 . Possibly, one of the two cacospongienones is an artifact, as these two terpenoids interconvert on standing. This is the first finding of linear C₂₁ difuran terpenoids, which are typical of the Spongiidae, in a member of the family Thorectidae.     

A stereoselective synthesis of silylated epoxycyclopentanols bearing four contiguous stereogenic centers

A palladium-catalyzed Tsuji-Trost alkylation of (E)-2-triethylsilyl-1,4-diacetoxy-but-2-ene with tert-butyl methyl malonate has been performed in excellent chemo and stereoselectivities. The allylated product has been further transformed in few steps in silylated epoxycyclopentanols bearing four controlled stereogenic carbons. The key reaction is a mild tandem oxidation-aldolization induced by DMP or IBX reagents.     

In Vitro Activity of Essential Oils Distilled from Colombian Plants against Candida auris and Other Candida Species with Different Antifungal Susceptibility Profiles

Multi-drug resistant species such as Candida auris are a global health threat. This scenario has highlighted the need to search for antifungal alternatives. Essential oils (EOs), or some of their major compounds, could be a source of new antifungal molecules. The aim of this study was to evaluate the in vitro activity of EOs and some terpenes against C. auris and other Candida spp. The eleven EOs evaluated were obtained by hydro-distillation from different Colombian plants and the terpenes were purchased. EO chemical compositions were obtained by gas chromatography/mass spectrometry (GC/MS). Antifungal activity was evaluated following the CLSI standard M27, 4th Edition. Cytotoxicity was tested on the HaCaT cell line and fungal growth kinetics were tested by time–kill assays. Candida spp. showed different susceptibility to antifungals and the activity of EOs and terpenes was strain-dependent. The Lippia origanoides (thymol + p-cymene) chemotype EO, thymol, carvacrol, and limonene were the most active, mainly against drug-resistant strains. The most active EOs and terpenes were also slightly cytotoxic on the HaCaT cells. The findings of this study suggest that some EOs and commercial terpenes can be a source for the development of new anti-Candida products and aid the identification of new antifungal targets or action mechanisms.     

The Modulation of PCSK9 and LDLR by Supercritical CO2 Extracts of Mentha longifolia and Isolated Piperitone Oxide,an In Vitro Study

In the present study the ability of supercritical carbon dioxide (SCO₂) extracts of M. longifolia L. leaves to modulate low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) expression was evaluated in cultured human hepatoma cell lines Huh7 and HepG2. Two SCO₂ extracts, one oil (ML-SCO₂) and a semisolid (MW-SCO₂), were subjected to detailed chemical characterization by mono- and bidimensional nuclear magnetic resonance (1D, 2D-NMR), gas chromatography coupled with mass spectrometry (GC-MS) and liquid chromatography coupled with mass spectrometry (LC-MS). Chemical analysis revealed significant amounts of fatty acids, phytosterols and terpenoids. ML-SCO₂ was able to induce LDLR expression at a dose of 60 µg/mL in HuH7 and HepG2 cell lines. Furthermore, ML-SCO₂ reduced PCSK9 secretion in a concentration-dependent manner in both cell lines. Piperitone oxide, the most abundant compound of the volatile constituent of ML-SCO₂ (27% w/w), was isolated and tested for the same targets, showing a very effective reduction of PCSK9 expression. The overall results revealed the opportunity to obtain a new nutraceutical ingredient with a high amount of phytosterols and terpenoids using the SCO₂ extraction of M. longifolia L., a very well-known botanical species used as food. Furthermore, for the first time we report the high activity of piperitone oxide in the reduction of PCSK9 expression.     

Neighbouring-group participation as the key step in the reactivity of acyclic and cyclic salicyl-derived O,O-acetals with 5-fluorouracil. Antiproliferative activity, cell cycle dysregulation and apoptotic induction of new O,N-acetals against breast cancer cells

The reaction between o-(hydroxymethyl)phenoxyacetaldehyde dimethyl acetals, or 3-methoxy-2,3-dihydro-5H-1,4-benzodioxepins with 5-fluorouracil (5-FU), has been studied. The intramolecular cyclization may be explained through a neighboring group attack to give a 2-(5-fluorouracil-1-yl)oxyranium ion that can be attacked by the silylated benzylic hydroxy group to yield the benzannelated seven-membered O,N-acetals. The formation of a macrocyclic trans-bis(5-FU O,N-acetal) is also reported. Such a compound arrested the human MCF-7 breast cancer cells at the G_o/G₁ phase of the cell cycle. On the contrary, the acyclic nitro O,N-acetal seems to work as a 5-FU prodrug, because it arrested cancer cells at the S phase as the well-known prodrug Ftorafur does.     

Synthesis and reactions of silicon containing cyclic α-amino acid derivatives

A simple synthesis of a new amino acid derivative 5,6-bis(trimethylsilyl)indanylglycine via cobalt mediated [2 + 2 + 2] cycloaddition strategy is described. Co-trimerization of diyne building block containing amino acid moiety with bis(trimethylsilyl)acetylene in presence of CpCo(CO)₂ catalyst afforded the silylated indane-based α-amino acid (AAA) derivative. Electrophilic aromatic substitution reaction, ipso to the trimethylsilyl group gave highly functionalised indane-based AAA derivatives.