Cytotoxic cembranoids from the Red Sea soft coral, Sarcophyton auritum

Chemical investigation of the Red Sea soft coral Sarcophyton auritum led to the isolation and structure elucidation of two new diterpene cembranoids; 2-epi-sarcophine (2) and (1R,2E,4S,6E,8R,11R,12R)-2,6-cembradiene-4,8,11,12-tetrol (4), as well as two known diterpene cembranoids, reported for the first time from this species, namely sarcophine (1) and (+)-7α,8β-dihydroxydeepoxysarcophine (3). Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The isolated cembranoids were found to display high cytotoxicity against HepG2 (liver cancer cell line) and MCF-7 (breast cancer cell line).     

Total syntheses of (R)-argentilactone and (R)-goniothalamin via catalytic enantioselective allylation of aldehydes

The total syntheses of (R)-argentilactone (five steps, 25% overall yield) and (R)-goniothalamin (three steps, 61% overall yield) have been described through the enantioselective catalytic allylation of aldehydes (including a propargylic aldehyde) which provided a rapid access to these natural products that display very interesting biological activities.     

Synthesis and odor of optically active trans-2,2,6-trimethylcyclohexyl methyl ketones and their related compounds

The synthesis characterized by cationic olefin cyclizations accomplished using ketone enol esters and odor of novel (1R,6S)- and (1S,6R)-2,2,6-trimethylcyclohexyl methyl ketones (5) are described. The stereoselective syntheses of (E)-(1R,6S)- and (E)-(1S,6R)-1-(2,2,6-trimethylcyclohexyl)-2-buten-1-one (6) and (1R,6S)-ethyl 2,2,6-trimethylcyclohexylcarboxylate (7), useful raw materials for flavor and fragrance, starting from the (1R,6S)- and (1S,6R)-5 are also described.     

Synthesis and structural characterization of a dichloro zinc complex of N,N′-bis-(2,6-dichloro-benzyl)-(R,R)-1,2-diaminocyclohexane: Application to ring opening polymerization of rac-lactide

A novel dichloro zinc complex (L¹)ZnCl₂, where L¹ is N,N′-bis-(2,6-dichloro-benzyl)-(R,R)-1,2-diaminocyclohexane, has been synthesized and characterized. The dimethyl derivatives, generated in situ from the well characterized dichloro zinc complexes (L¹)ZnCl₂ and (L²)ZnCl₂, where L² is N,N′-bis-(benzyl)-(R,R)-1,2-diaminocyclohexane, were employed as initiators for the ring opening polymerization (ROP) of rac-lactide (rac-LA). The complexes were found to be highly efficient initiators yielding the polylactide (PLA) with a narrow molecular weight distribution. The catalytic activity and heterotactic selectivity of the Zn(II) complexes were affected by the substituents on the phenyl groups of benzyl moieties in (R,R)-1,2-diaminocyclohexane. The dimethyl derivative of (L²)ZnCl₂ produced highly stereocontrolled PLA with P_r = 0.75 at −25 °C.     

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of common cutworm (Spodoptera litura)

Biotransformation of (+)-(1R,2S)-fenchol by the larvae of Spodoptera litura was carried out. Substrate was converted to three new terpenoids, (+)-(1R,2S)-10-hydroxyfenchol, (+)-(1R,2R,3S)-8-hydroxyfenchol and (−)-(1S,2S,6S)-6-exo-hydroxyfenchol, and one known terpenoid, (−)-(1R,2R,3R)-9-hydroxyfenchol. These structures were established by NMR, IR, specific rotation and mass spectral studies.     

Radical mediated stereoselective synthesis of (4R,8R)-4,8-dimethyldecanal, an aggregation pheromone of Tribolium flour beetles

(4R,8R)-4,8-Dimethyldecanal, a common aggregation pheromone of Tribolium flour beetles, has been synthesized from (R)-2,3-O-isopropylideneglyceraldehyde in 11 steps and 7% overall yield. The key step in the synthesis is the highly diastereoselective chelation-controlled radical reaction of ethyl (4S,5R)-4-benzyloxy-5,6-(isopropylidenedioxy)-2-methylenehexanoate with ethyl (R)-5-iodo-3-methylpentanoate performed in the presence of 7 equiv of MgBr₂·OEt₂.     

Crystal chemistry and crystallography of the SrR2CuO5 (R=lanthanides) phases

The crystal chemistry and crystallography of the compounds SrR₂CuO₅ (Sr-121, R=lanthanides) were investigated using the powder X-ray Rietveld refinement technique. Among the 11 compositions studied, only R=Dy and Ho formed the stable SrR₂CuO₅ phase. SrR₂CuO₅ was found to be isostructural with the “green phase”, BaR₂CuO₅. The basic structure is orthorhombic with space group Pnma. The lattice parameters for SrDyCuO₅ are a=12.08080(6) Å, b=5.60421(2) Å, c=7.12971(3) Å, V=482.705(4) Å³, and Z=8; and for the Ho analog are a=12.03727(12) Å, b=5.58947(7) Å, c=7.10169(7) Å, V=477.816(9) Å³, and Z=8. In the SrR₂CuO₅ structure, each R is surrounded by seven oxygen atoms, forming a monocapped trigonal prism (RO₇). The isolated CuO₅ group forms a distorted square pyramid. Consecutive layers of prisms are stacked in the b-direction. Bond valence calculations imply that residual strain is largely responsible for the narrow stability of the SrR₂CuO₅ phases with R=Dy and Ho only. X-ray powder reference diffraction patterns for SrDy₂CuO₅ and SrHo₂CuO₅ were determined.     

(1R,2R)-DPEN-derived triazolium salts for enantioselective oxodiene Diels-Alder reactions

Enantioselective oxodiene Diels-Alder reactions catalyzed by (1R,2R)-DPEN-derived triazolium salts were realized successfully. With 0.5 mol % of (1R,2R)-DPEN-derived triazolium salt C and 150 mol % of Et₃N, the reactions of various α-chloroaldehydes (α-bromoaldehyde) with substituted enones led to 3,4-dihydropyridinones and their derivatives in good yields, diastereoselectivities, and enantioselectivities (up to 97% ee).     

Effects of residual metal compounds and chain-end structure on thermal degradation of poly(3-hydroxybutyric acid)

Thermal degradation behaviours of poly(3-hydroxybutyric acid) (P(3HB); bacterial poly[(R)-3-hydroxybutyric acid] and synthetic poly[(R,S)-3-hydroxybutyric acid] samples, were examined under both isothermal and non-isothermal conditions. The inverse of number-average degree of polymerisation for all P(3HB) samples decreased linearly with degradation time during the initial stage of isothermal degradation at a temperature ranging from 170-190 °C. In addition, crotonyl unit was detected in the residual polymer samples as main ω-chain-end. These results indicate that the dominant thermal degradation reaction for P(3HB) is a random chain scission via cis-elimination reaction of P(3HB) molecules. It was found that the presence of either Ca or Mg ions enhances the depolymerisation of P(3HB) molecules, while that Zn ions hardly catalyse the reaction. As a result, a shift of thermogravimetric curves toward the lower temperature regions was observed for the P(3HB) samples containing high amounts of Ca and Mg compounds.     

Stereoselective synthesis of α-hydroxy-β-amino acid derivatives from β-hydroxy-γ,δ-unsaturated sulfilimine

The first report on the use of N-sulfinyl benzylcarbamate for the preparation of N-Cbz sulfilimine from the corresponding sulfoxide is reported. The sulfilimine moiety is utilized as an intramolecular nucleophile for the regio- and stereoselective heterofunctionalization of an alkene to furnish a bromo carbamate which is used as a key advanced intermediate in the synthesis of representative α-hydroxy-β-amino acid derivatives.     

Phase equilibria and crystal chemistry of the R-Cu-Ti-O systems (R=lanthanides and Y)

As part of the study of interaction of the Ba₂RCu₃O_6+z (R=lanthanides and Y) superconductor with SrTiO₃ buffer, phase equilibria of the subsystem, R₂O₃-TiO₂-CuO (R=Nd, Y, and Yb), have been investigated in air at 960 °C. While the phase relationships of the two phase diagrams with smaller R (Y and Yb) are similar, substantial differences were found in the Nd₂O₃-TiO₂-CuO system, partly due to different phase formation in the binary R₂O₃-TiO₂ and R₂O₃-CuO systems. R₂CuTiO₆ and R₂Cu₉Ti₁₂O₃₆ were the only ternary phases established in all the three diagrams. R₂Cu₉Ti₁₂O₃₆ belongs to the perovskite-related [AC₃](B₄)O₁₂ family which is cubic Im3. Depending on the size of R³⁺, R₂CuTiO₆ crystallizes in two crystal systems: Pnma (R=La-Gd), and P6₃cm (R=Dy-Lu). The structure and crystal chemistry of the Pnma series of R₂CuTiO₆ (R=La, Nd, Sm, Eu, and Gd) are discussed in detail in this paper. Patterns for selected members of R₂CuTiO₆ have also been prepared and submitted for inclusion in the Powder Diffraction File (PDF).     

Stereoselective total synthesis of the (Z)-isomer of a novel phytotoxic nonenolide from Phomopsis sp. HCCB03520 and its C-6 epimer

The (Z)-isomer of a phytotoxic nonenolide, (6S,7R,9R)-6,7-dihydroxy-9-propylnon-4-eno-9-lactone isolated from Phomopsis sp. HCCB03520 and its C-6 epimer have been synthesized through a common route starting from butyraldehyde. The synthesis involves enantioselective Maruoka allylation, Sharpless asymmetric epoxidation and intramolecular ring closing metathesis as the important steps.     

Sequential Baylis-Hillman/RCM protocol for the stereoselective synthesis of (+)-MK7607 and (+)-streptol

Sequential Baylis-Hillman/ring-closing metathesis (RCM) approach toward the total synthesis of (+)-MK7607 and (+)-streptol starting from (R,R)-tartaric acid is reported.     

Subsolidus phase relations and crystal structures of R-Ca-Cu-O (R=Nd, Sm, Gd, Tm) systems

The subsolidus phase relations of R₂O₃-CaO-CuO ternary systems (R=Nd, Sm, Gd, Tm) have been investigated by X-ray powder diffraction. All samples were synthesized at about 950° in air. There exists a ternary compound Ca_14−xR_xCu₂₄O₄₁ (x = 4 for R=Nd, Gd and x = 5 for R = Sm) and a ternary solid solution Ca_2+xR_2−xCu₅O₁₀ (R=Nd, Sm, Gd, Tm) with a wide composition range Δx of about 0.6. The compound Ca_14−xR_xCu₂₄O₄₁ possesses a layered orthorhombic structure and is isostructural to Sr_14−xCa_xCu₂₄O₄₁. The lattice parameters a and c of the compound are basically independent of the ionic radius of R, while the lattice parameter b and unit-cell volume V decrease substantially with the decrease of the ionic radii of R. The Ca_2+xR_2−xCu₅O₁₀ solid solution is isostructural to Ca_2+xY_2−xCu₅O₁₀, the structure of which is based on an orthorhombic “NaCuO₂-type” subcell containing infinite one-dimensional chains of edge-shared square planar cuprate groups crosslinked by the layered cations Ca and R that locate in the inter-chain tunnels.     

Stereocontrolled synthesis of (±)-methyl 3,6-epoxy-4,6,8-triethyl-2,4,9-dodecatrienoate, a major metabolite of Caribbean sponge, Plakortis halichondrioides, using reactions of alkylidenecarbenes in one pot

(±)-Methyl (2Z,6R*,8R*,9E)-3,6-epoxy-4,6,8-triethyl-2,4,9-dodecatrienoate, a major metabolite of the Caribbean sponge, was synthesized in a stereocontrolled manner from γ-caprolactone. The key step was one-pot generation of alkylidenecarbenes at two sites followed by 1,2 hydride shift and intramolecular 1,5 C-H insertion.     

Isolation, structural elucidation and synthesis of a novel antioxidative pseudo-di-peptide, Hanasanagin, and its biogenetic precursor from the Isaria japonica mushroom

The entomogenous ‘Hanasanagitake’ mushroom, Isaria japonica, is used as a folk medicine and as a traditional health food choice in Japan. A search for naturally occurring antioxidative compounds from the mushroom led to the isolation of a novel pseudo-di-peptide, named Hanasanagin, and a possible biogenetic precursor. The structures of the pseudo-di-peptides were determined as (R)-3,4-diguanidinobutanoyl-(S)-DOPA and (R)-3,4-diguanidinobutanoyl-(S)-tyrosine by spectral analysis, chemical synthesis and enzymatic conversion.     

New stereoselective synthesis of thiamphenicol and florfenicol from enantiomerically pure cyanohydrin: a chemo-enzymatic approach

Thiamphenicol and florfenicol have been synthesized stereoselectively from enantiomerically pure 4-methylsulfanyl-mandelonitrile, which was obtained by hydrocyanation reaction of 4-methylsulfanyl-benzaldehyde catalyzed by (R)-hydroxynitrile lyase of Badamu (Prunus communis L. var. dulcis Borkh, almond from Xinjiang, China). It was found to be a highly effective bio-catalyst for this reaction after an extensive screening.     

The fragmentation reaction of 16R-bromopregnane-3S,20S-diol

16R-Bromopregnane-3S,20S-diol reacted with potassium t-butoxide to afford androst-16-en-3S-ol in a moderate yield via fragmentation reaction. The latter is a key intermediate for the synthesis of 5α-androst-16-en-3-one, as boar sex pheromone, and other steroidal drugs. In addition, 16R,20S-epoxypregnane-3S-ol was also obtained as a major product by changing the reaction solvent.     

Stereoselective synthesis of (+)-(8R,8aR)-perhydro-8-indolizidinol

A highly stereoselective total synthesis of (+)-(8R,8aR)-perhydro-8-indolizidinol is described. Key steps involved in this synthesis are diastereoselective zinc allylation, azido-olefin cyclization and reductive amination followed by cyclization which effectively constructed the indolizidine ring. This contributes a unique approach to the synthesis of indolizidine alkaloids that offers the advantages of brevity and relatively high overall yields.     

Practical synthesis of (2S,3R)-3-hydroxy-3-methylproline, a constituent of papuamides, using a diastereoselective tandem Michael-aldol reaction

(2S,3R)-3-Hydroxy-3-methylproline, a constituent of cyclodepsipeptides polyoxypeptins A and B, was efficiently synthesized by lithium chloride-induced diastereoselective tandem Michael-aldol reaction using methyl vinyl ketone and N-1-naphthylsulfonylglycine (R)-binaphthyl ester and subsequent hydrolysis of the product in 39% overall yield and five steps.