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Terpenoid spiroethers are abundant natural flavors with significant impact, particularly in the food industry. We present in this article the synthesis of new derivatives of the well-known flavors theaspirane and vitispirane using a variant of the Prins cyclization starting from α,β-unsaturated or heterocyclic ketones. When aromatic ketones were used as the starting materials for Lewis acid-mediated cyclizations, an alternative pathway involving a domino sequence of Prins cyclization, followed by an intramolecular Friedel--Crafts alkylation, gave benzoannelated oxabicyclo[3.3.1]nonane derivatives. Different reaction pathways may be triggered by the reaction temperature to give with good selectivity either tetrahydropyran derivatives as conventional Prins products or oxabicyclo[3.3.1]nonane derivatives. [ABSTRACT FROM AUTHOR]

Triterpenoids comprise a very diverse family of polycyclic molecules that is well-known to possess a myriad of medicinal properties. Therefore, triterpenoids constitute an attractive target for medicinal chemistry and diversity-oriented synthesis. Photochemical transformations provide a promising tool for the rapid, green, and inexpensive generation of skeletal diversity in the construction of natural product-like libraries. With this in mind, we have developed a diversity-oriented strategy, whereby the parent triterpenoids bryonolic acid and lanosterol are converted to the pseudosymmetrical polyketones by sequential allylic oxidation and oxidative cleavage of the bridging double bond at the B/C ring fusion. The resultant polyketones were hypothesized to undergo divergent Norrish-Yang cyclization to produce unique 6/4/8-fused triterpenoid analogues. The subtle differences between parent triterpenoids led to dramatically different spatial arrangements of reactive functionalities. This finding was rationalized through conformational analysis to explain unanticipated photoinduced pinacolization, as well as the regio- and stereochemical outcome of the desired Norrish-Yang cyclization. [ABSTRACT FROM AUTHOR]

As a result of a combined theoretical and experimental study, we describe a two-step protocol for the preparation of an optically pure, multifunctional, cyclopentanic core shared by a number of natural products. This process is based on a hitherto unreported Ti (III)-mediated diastereoselective cyclization in which the hydroxy-directed template effect played by the Ti (III) species was found to be crucial for the stereoselective outcome of the reaction. The viability of this concept was confirmed with the first protecting-group free synthesis of three enantiopure chokols, namely, chokols K, E, and B. [ABSTRACT FROM AUTHOR]

Terpene synthascs are responsible for a large diversity of terpene carbon skeletons found in nature. The multiproduct sesquiterpene synthase MtTPS5 isolated from Medicago truncatula produces 27 products from farnesyl diphosphate (1, FDP). In this paper, we report the reaction steps involved in the formation of these products using incubation experiments with deuterium-containing substrates; we determined the absolute configuration of individual products to establish the stereochemical course of the reaction cascade and the initial conformation of the cycling substrate. Additional labeling experiments conducted with deuterium oxide showed that cadalane sesquitcrpenes are mainly produced via the protonation of the neutral intermediate germacrene D (5). These findings provide an alternative route to the general accepted pathway via nerolidyl diphosphate (2, NDP) en route to sesquiterpenes with a cadalane skeleton. Mutational analysis of the enzyme demonstrated that a tyrosine residue is important for the protonation process. [ABSTRACT FROM AUTHOR]

An efficient access to 2-isobetulin, 2-isobetulinic acid, 2-isooleanolic acid, and 2-isoursolic acid has been developed. The key step is a novel one-pot conversion of 2,3-dihydroxy triterpenes to 3-deoxy-2-oxo triterpenes. This method provides a new access to 3-deoxy-2-substituted pentacyclic triterpenes as potential therapeutic agents against metabolic diseases, tumors, and HIV infection. [ABSTRACT FROM AUTHOR]

A general preparation method of the all-(E)-polyprenols 12 has been developed from readily available geranyl sulfone by the chain-extension process utilizing the C5 unit 5 and the chain-termination process utilizing the C5 unit 10 together with the chemoselective reductive desulfonylation. The polyprenols 12 were converted to compounds 3 containing two consecutive prenyl sulfone moieties at the tail end, which underwent the controlled electrophilic cyclization only at the carbon-carbon double bonds that were remote from the flat and rigid benzenesulfonyl groups. [ABSTRACT FROM AUTHOR]

The reaction of natural product derived propargylic alcohols with CpCo(CO)2 produces three new types of natural product hybrids having two or three terpene or steroid fragments. The tether joining the natural product subunits is built during the reaction. Type 1 hybrids have two terpene or steroid moieties joined by a CpCo-cyclobutadiene tether, with the two units disposed in a 1,2-arrangement (9, 14, 22). Type 2 hybrids have a Co-cyclopentadienone tether (10). Type 3 has three units of terpene or steroid joined to a benzene ring (11, 12, 15). An unusual Co-mediated β-carbon elimination pathway of propargylic alcohols leading to ketones (an unknown process in this chemistry) has been observed. [ABSTRACT FROM AUTHOR]

Total syntheses of two new (±)-kempane derivatives 30 and 47 were achieved with transannular Diels-Alder reaction (TADA) serving as the key step for the stereoselective formation of tricyclic [6.6.5J system 3. This synthetic approach also reveals that the geometry of the C3 group of such a tricyclic system plays an important role for the formation of the seven-membered kempane skeleton. [ABSTRACT FROM AUTHOR]

The complex 8 of isopinocampheylborane and p-(dimethyl-amino)pyridine (DMAP) can be obtained with >99% ee starting from α-pinene with 80–90% ee by hydroboration using DMAP·BH3 (5) activated by 5% iodine, or by the conventional hydroboration of α-pinene, followed by addition of DMAP. Purification of the air-stable 8 is readily accomplished by crystallization from methanol. Conversion of 8 into the trifluoroborate adduct 1 using KHF2 occurs without erosion of ee. Generation of the derived 2 in situ with TMSC1 as the fluorophile also occurs with little, if any, loss of ee, as evidenced by the preparation of the salicaldimine complex 11 and the derived amino alcohol 12 with 94% ee overall. [ABSTRACT FROM AUTHOR]

Regioselective halogenation of the terminal isopropylidene unit of different acyclic polyolefinic polyprenoids (farnesyl acetate, geranylgeranyl acetate, squalene, etc.) using NCS/catalytic polymer-supported selenenyl bromide is described; good to excellent yields are obtained (68–96%). The first applications of this protocol include the concise synthesis of bioactive terpenoids 1–3. [ABSTRACT FROM AUTHOR]

The biosynthesis of geosmin (1) and (1(10)E,5E)-germacradien-11-ol (2), two volatile terpenoid compounds emitted by the myxobacteria Myxococcus xanthus and Stigmatella aurantiaca, was investigated in feeding experiments with different labeled precursors. In these experiments, the volatiles released by the cell cultures grown on agar plates were collected with a closed-loop stripping apparatus (CLSA) and analyzed by GC-MS. [²H10]Leucine and [4,4,4,5,5,5-²H6]dimethylacrylate were fed to wild-type strains and bkd mutant strains, which are impaired in the degradation of leucine to isovaleryl-CoA. [²H10]Leucine was incorporated into 1 and 2 only by the wild-type strains via the biosynthetic pathway that involves leucine degradation and branching into the mevalonate pathway. Dimethylacrylyl-CoA (DMA-CoA) is an intermediate in the leucine degradation and in the recently discovered pathway from HMG-CoA to isovaleryl-CoA. The corresponding free acid, [4,4,4,5,5,5-²C;H6]dimethylacrylic acid, was incorporated into 1 and 2 only by the mutants impaired in leucine degradation. [4,4,6,6,6-²H5]Mevalonic acid lactone (12) was synthesized and fed to M. xanthus and S. aurantiaca wild-type strains and a double mutant strain of M. xanthus. This strain does not degrade leucine and is impaired in the reduction of 3-hydroxy-3-methylglutaryl-CoA to mevalonic acid. The mass spectral analysis of labeled 1 and 2 obtained in these feeding experiments led to a biosynthetic scheme to 1 with intermediate 2. This pathway differs from that observed in the liverwort Fossombronia pusilla and thus suggests microbial geosmin biosynthesis following a route different from that in liverworts. Our results are supported by a 1,2-hydride shift of the tertiary hydrogen atom at C-4a into the ring opposite to that in F. pusilla. [ABSTRACT FROM AUTHOR]

We describe a novel convergent procedure that has proved useful in the synthesis of a wide range of meroterpenoid-related structures containing a mono-, ses- qui-, or diterpenoid moiety linked to a nonfused aromatic subunit with various substitution patterns. The key steps were the Stille-type coupling of aryl stannanes and allylic carbonates, followed by the titanocene-catalyzed domino cyclization of aryl epoxypolyprenes. The coupling reaction was perfectly compatible with preformed epoxides, while the sequential cyclization, which presumably proceeded via alkyl radicals inert to benzene derivatives, selectively provided exocyclic alkenes. [ABSTRACT FROM AUTHOR]

A novel terpenoid-related compound, stolonilactone (1), was isolated from the Okinawan soft coral Clavularia koellikeri. The structure of I was elucidated on the basis of spectroscopic analysis. A possible biogenesis of 1 through the [4 + 2]-cycloaddition of a trisnorsesquiterpenoid-type diene and a cembranolide-type dienophile is proposed. [ABSTRACT FROM AUTHOR]

An asymmetric total synthesis of (+)-chatancin was achieved via a transannular Diels-Alder (TADA) reaction of an in situ generated macrocyclic pyranophane pseudobase. The presented route constitutes the second of two proposed biosynthetic pathways that involves a TADA reaction. It links this diterpene biogenetically to the cembranoids. A set of TADA selection rules that rationalize the formation of (+)-chatancin from a dynamic equilibrium of four 2-hydroxy-2H-pyrane bicycles and their 16 potential TADA transition states are also outlined. Beyond the TADA reaction, highlights of the synthetic work include the assembly of a chiral acyclic macrocyclization substrate from (S)-citronellol and an efficient macrocyclization via a β-ketosulfoxyde/enone Michael addition. [ABSTRACT FROM AUTHOR]