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Scalarane sesterterpenoids emerged as interesting bioactive natural products which were isolated extensively from marine sponges and shell-less mollusks. Some representatives were also reported recently from superior plants. Many scalarane sesterterpenoids displayed a wide spectrum of valuable properties, such as antifeedant, antimicrobial, antifungal, antitubercular, antitumor, anti-HIV properties, cytotoxicity and stimulation of nerve growth factor synthesis, as well as anti-inflammatory activity. Due to their important biological properties, many efforts have been undertaken towards the chemical synthesis of natural scalaranes. The main synthetic challenges are connected to their complex polycyclic framework, chiral centers and different functional groups, in particular the oxygenated functional groups at the C-12 position, which are prerequisites of the biological activity of many investigated scalaranes. The current work addresses this problem and the synthesis of 17-oxo-20-norscalaran-12α,19-O-lactone is described. It was performed via the 12α-hydroxy-ent-isocopal-13(14)-en-15-al obtained from (-)-sclareol as an accessible starting material. The tetracyclic lactone framework was built following an addition strategy, which includes the intramolecular Michael addition of a diterpenic acetoacetic ester and an intramolecular aldol condensation reaction as key synthetic steps. The structure and stereochemistry of the target compound have been proven by X-Ray diffraction method.

Synthesis of polyfunctional triterpene derivative [8(27),13E,17E,21E]-15-phenylsulfonyl-16-oxobicyclofarnesylfarnesol benzyl ether (8) from commercially available monoterpene geraniol and diterpene manool has been accomplished in 73% yield and its chemical transformation in superacid medium has been investigated. An unexpected rearrangement of 8 occurred, which involved methyl migration in the bicyclic fragment and total inhibition of the lateral polienic chain. A new bicyclic triterpene product [5(10),13E,17E,21E]-15-phenylsulfonyl- 16-oxo-30(10→9)-abeo-bicyclofarnesylfarnesol benzyl ether (9), with rearranged new carbon skeleton has been obtained. Its bicyclic moiety is analogous to this of a natural triterpene neopolypodatetraene.

The content of known tetra- and pentacyclic diterpenoids in extracts of sunfl ower (Helianthus annuus L.) dry wastes has been studied using different solvents for extraction. It was established that the largest extracted quantity of ent-kaur-16-en-19-oic acid is obtained when ethanol and diethyl ether are used for extraction of the plant material.

A relatively simple method for isolation of the mixture of ent-kaur-16-en-19-oic (1) and ent-trachiloban-19-oic (2) acids from dry waste of sunflower processing has been elaborated, and it has been shown that the waste can serve as an accessible source of ent-kauranic and ent-trachilobanic diterpenoids.

Tratarea în prealabil a bentonitului Lărguţa cu soluţie diluată de acid (pH 2), în continuare fiind intercalat cu specii oligomerice de aluminiu, duce la modificarea proprietăţilor de suprafaţă ale adsorbanţilor intercalaţi – a acidităţii lor, a caracteristicilor sorbţional-structurale şi a stabilităţii termice. Cinetica conversiei acidului oleic la esterificarea cu alcool etilic este influenţată de caracterul acid al catalizatorilor utilizaţi. Modelările efectuate relevă că adsorbanţii intercalaţi, obţinuţi pe baza bentonitului Lărguţa, au perspective reale de a fi utilizaţi pentru obţinerea biocombustibilului din uleiuri vegetale.SURFACE PROPERTIES OF PILLARED BENTONITE LARGUTA (R. MOLDOVA) PILLARED WITH ALUMINUM OLIGOMERIC SPECIESLarguta bentonite prior treatment with dilute acid (pH 2) further being pillared with aluminum oligomeric species, result in modification of the surface properties of the adsorbents - acidity, sorption-structural characteristics and thermal stability. The kinetics of the conversion of oleic acid to esterification with ethylic alcohol is influenced by the nature of the acid catalysts used. Pillared adsorbents obtained on the basis of bentonite Larguta (RM) possess real prospects for obtaining bio-fuel from vegetable oils.

A review of diterpenoid cyclization initiated by electrophilic reagents is provided. Conventional protonic and Lewis acids are examined along with superacids as initiators of cyclization cascade. An emphasis is placed on the use of cyclization reactions as a tool for the synthesis of compounds with potential practical utility. The review contains 74 references.

The current communication represents an extended abstract of the presentation delivered on the joint Moldo-Italian seminar “New frontiers in natural product chemistry”, held in the Institute of Chemistry, Academy of Sciences of Moldova on 31 September. An overview of the synthetic methods oriented to the synthesis of functionalized terpenic perhydrindanes is provided. Different synthetic strategies are considered, including those based on biomimetic approach. The array of obtained new structures can serve as leads in structure-activity studies as well as useful building blocks towards other perhydrindanes.

A selective rearrangement of a epoxy-homodrimanic substrate is described. Using fluorosulfonic acid at low temperature leads by ring contraction to a perhydrindanic structure. On the contrary, using boron trifluoride-diethyl ether at r.t. selectively brings about angular methyl migration.

The known diterpenic ester – 15α-angeloyl-ent-kaur-16-en-19-oic (angeloylgrandifl oric) acid has been isolated from the dry wastes of Helianthus annuus L. The synthesis of 15α-hydroxy- and 15-oxo-ent-kaur-16-en-19- oic acids starting from ent-kaur-16-en-19-oic acid has been performed.

An efficient retro-biomimetic procedure for the synthesis of two natural products having atisanic and beyeranic structure is reported. The readily available ent-kaurenoic acid is used as the substrate, which provides under superacidic treatment a mixture of natural ent-beyer-15-en-19-oic and ent-atis-16-en-19-oic acids. These compounds have been reported as components of medicinal plants and possess relevant biological activity. Their structure was confirmed on the basis of chemical transformations and spectral data.

Conjugate 1,4-addition of N-bromosuccinimide (NBS) to a diene system, possessing a suitable oxygen functionality, leads to functionalized tetrahydrofuran derivatives, which can be further derivatized into different synthetic targets.

The synthesis of tetra- and pentanorlabdane compounds with rearranged cycle B based on commercially available (+)-sclareolide is reported. Desired compounds were prepared from intermediate ketones via Baeyer–Villiger oxidation. The structures of synthesized compounds were confirmed by spectral IR, 1D (1H, 13C, and DEPT), and 2D (H-COSY, H,C-HSQC, H,C-HMBC, H,N-HMBC, NOESY) NMR analyses, mass-spectrometry and single crystal X-rays diffraction. Two out of the four synthesized compounds showed high antifungal and antibacterial activities comparable to and exceeding standard antifungal (caspofungin) and antibacterial (kanamycin) agents. DFT calculations show that in gas and DCM, compound 4 is more stable than 3 with a difference in the Gibbs free energy of 23.3 kJ/mol and 20.7 kJ/mol, respectively. In water and methanol, compound 3 is slightly more stable, by 2.4 kJ/mol and 2.78 kJ/mol, respectively. Molecular docking to four targets DNA gyrase from E. coli (1KZN), Fabz from P. aeruginosa (1U1Z), dihydrofolate reductase from C. albicans (3QLS) and MurB from E. coli (2Q85) showed good agreement with the results of in vitro evaluation and confirmed the biological activity of compounds 3 and 4, with binding affinities comparable and for some targets exceeding that of Caspofungin and Kanamycin.

The selective one-step synthesis of 13-epi-manoyl oxide is reported based on a low-temperature superacidic cyclization of sclareol. The reaction conditions have been finely tuned in order to achieve a 9:1 ratio between epimeric oxides in favor of the desired 13-epi-oxide.

Herein we report a feasible study concerning the synthesis and the in vitro antimicrobial activity of some new homodrimane sesquiterpenoids with a benzimidazole unit. Based on some homodrimane carboxylic acids, on their acyl chlorides and intermediate monoamides, a series of seven N-homodrimenoyl-2-amino-1,3-benzimidazoles and 2-homodrimenyl-1,3-benzimidazoles was synthesized. The syntheses involved the decarboxylative cyclization and condensation of the said acids or acyl chlorides with o-phenylendiamine and 2-aminobenzimidazole, as well as the p-TsOH-mediated cyclodehydration of the said monoacylamides. The structures of the synthesized compounds have been fully confirmed, including by the X-ray diffraction. Their biological activities were evaluated on five species of fungi (Aspergillus niger, Fusarium solani, Penicillium chrysogenum, P. frequentans, and Alternaria alternata) and two strains of bacteria (Bacillus sp. and Pseudomonas aeruginosa). Compounds 7 and 20 showed higher antifungal (MIC = 0.064 and 0.05 μg/mL) and antibacterial (MIC = 0.05 and 0.032 μg/mL) activities compared to those of the standards: caspofungin (MIC = 0.32 μg/mL) and kanamycin (MIC = 2.0 μg/mL), and compounds 4, 10, 14, and 19 had moderate activities.

The biomimetic synthesis of sacculatane-type epimeric compounds 14a and 14b is reported. The key synthetic step is the low-temperature superacidic cyclization of (all-E)-ω-acetoxygeranylgeraniol 12 obtained in nine steps from geranyllinalool (13). The 19-acetoxysacculata-7,17-dien-11-ol (14a) could be an important and convenient starting compound for the synthesis of other sacculatane diterpenoids. [ABSTRACT FROM AUTHOR]

Methyl (2Z,6Z,10E,14E)- (3) and methyl (2E,6Z,10E,14E)-geranylfarnesoate (4) were prepared, and then individually cyclized in the presence of the superacid FSO3H. In the case of substrate 3, the scalaranic ester 9 (26%) and the cheilanthanic ester 10 (39%) were isolated. Under the same conditions, substrate 4 afforded a mixture of the corresponding stereoisomers 11 (25%) and 12 (63%). The observed product selectivity supports that the internal, (6Z)-configured C=C bond in these and other biologically relevant substrates plays an essential role in the cyclization process. [ABSTRACT FROM AUTHOR]

A convenient strategy for molecular editing of available ent-kauranic natural scaffolds has been developed based on radical mediated C–C bond formation. Iodine atom transfer radical addition (ATRA) followed by rapid ionic elimination and radical azidoalkylation were investigated. Both reactions involve radical addition to the exo-methylenic double bond of the parent substrate. Easy transformations of the obtained adducts lead to extended diterpenes of broad structural diversity and artificial diterpene-alkaloid hybrids possessing lactam and pyrrolidine pharmacophores. The cytotoxicity of selected diterpenic derivatives was examined by in vitro testing on several tumor cell lines. The terpene-alkaloid hybrids containing N-heterocycles with unprecedented spiro-junction have shown relevant cytotoxicity and promising selectivity indexes. These results represent a solid basis for following research on the synthesis of such derivatives based on available natural product templates.