A highly stereoselective preparation of CF3-substituted 1-aryl-1,2-diphenylethenes: application to the synthesis of panomifene

β-CF₃-α,β-diphenylvinyl sulfide 3a was prepared stereoselectively in 77% yield from the reaction of 2 with phenyllithium at room temperature for 5 h. Oxidation of 3a with MCPBA afforded the corresponding vinyl sulfone 4a, in which (E)-4a can be crystallized in a mixture of CH₂Cl₂ and hexane. The addition-elimination reaction of (E)-4a with phenyllithium having substituents on the benzene ring provided 5a-j in 51-82% yields stereospecifically. Similarly, the treatment of (E)-4a with p-chloroethoxyphenyllithium in the presence of 12-crown-4 (20 mol %) at −10 °C, followed by slowly warming to room temperature, resulted in the formation of the corresponding panomifene precursor 6 in 82% yield.     

Autoxidation of isotachysterol

Isotachysterol, the acid-catalyzed isomerization product of vitamin D₃, produces seven previously unknown oxygenation products in a self-initiated autoxidation reaction under atmospheric oxygen in the dark at ambient temperature. They are (5R)-5,10-epoxy-9,10-secocholesta-6,8(14)-dien-3β-ol (6a), (5S)-5,10-epoxy-9,10-secocholesta-6,8(14)-dien-3β-ol (6b), (10R)-9,10-secocholesta-5,7,14-trien-3β,10-diol (7a), (10S)-9,10-secocholesta-5,7,14-trien-3β,10-diol (7b), (7R,10R)-7,10-epoxy-9,10-secocholesta-5,8(14)-dien-3β-ol (8), 5,10-epidioxyisotachysterol (9) and 3,10-epoxy-5-oxo-5,10-seco-9,10-secocholesta-6,8(14)-dien-10-ol (10). The formation of these products is explained in terms of free radical peroxidation chemistry.     

Specific oxidation of C-14 oxygenated 4(20),11-taxadienes by microbial transformation

Three C-14 oxygenated taxanes, 2α,5α,10β,14β-tetraacetoxytaxa-4(20),11-diene (1), 2α,5α,10β-triacetoxy-14β-(2-methylbutyryloxy)taxa-4(20),11-diene (2), and yunanaxane (3), major products of callus cultures of Taxus spp., were regio- and stereoselectively hydroxylated at the 7β position by a fungus, Absidia coerulea IFO 4011. Intriguingly, when 1 was co-administered with β-cyclodextrin and incubated with the fungus cell cultures, three other compounds 5α,9α,10β,13α-tetraacetoxytaxa-4(20),11-dien-14β-ol (7), 5α,9α,10β,13α-tetraacetoxytaxa-4(20),11-dien-1β-ol (8) and 5α,9α,10β,13α-tetraacetoxy-11(15→1) abeotaxa-4(20),11-dien-15-ol (9) were obtained.     

Combined biotransformations of 4(20),11-taxadienes

Taxuyunnanine C (1) and its analogs (2 and 3), the C-14 oxygenated 4(20), 11-taxadienes from callus cultures of Taxus sp., were regio- and stereo-selectively hydroxylated at the 7β position by a fungus, Abisidia coerulea IFO 4011, and it was interesting that the longer the alkyl chain of the acyloxyl group at C-14 became, the higher the yield of 7β-hydroxylated product was. Besides the three 7β-hydroxylated products (5, 9, 17), other nine new products (7, 11, 12, 14, 15, 16, 18, 20 and 21) and six known products (4, 6, 8, 10, 13 and 19) were obtained. Subsequently, the acetylated derivatives (24 and 27) of 7β-and 9α-hydroxylated products of 1 were regio- and stereo-specifically hydroxylated at the 9α position by Ginkgo cells and 7β position by A. coerulea, respectively. Thus, the two specific oxidations have been combined. These bioconversions would provide not only valuable intermediates for the semi-synthesis of paclitaxel or other bioactive taxoids from 1 and its analogs, but also some useful hints for the biosynthetic pathway of taxoid in the natural Taxus plant.     

Novel reactions of lycoctonine analogs: unusual pyrolysis of C4-COOH and hydrogenolysis of N-C6 bond

Pyrolysis of carboxylic acid group at C-4 of 2, an oxidation product from the C₁₉-diterpenoid alkaloid lycoctonine 1, generated an unexpected but novel rearranged product 13 (37%). The structure of 13 was confirmed by its 2D NMR data and its single crystal X-ray crystallographic analysis. In addition, hydrogenolysis of 13 in the presence of acetic acid yielded the N-C6 bond fission products 16 and 17, which represents the first hydrogenolysis involving the breakage of the N-C6 bond of the diterpenoid alkaloids. Some new observations on the oxidation of lycoctonine 1 were described as well.     

Regio- and stereoselective reactions of a rhodanine derivative with optically active 2-methyl- and 2-phenyloxirane

The reaction of a rhodanine derivative (=(Z)-5-benzylidene-3-phenyl-2-thioxo-1,3-thiazolidin-4-one; 1) with (S)-2-methyloxirane (2) in the presence of SiO₂ in dry CH₂Cl₂ for 10 days led to two diastereoisomeric spirocyclic 1,3-oxathiolanes 3 and 4 with the Me group at C(2) (Scheme 2). The analogous reaction of 1 with (R)-2-phenyloxirane (5) afforded also two diastereoisomeric spirocyclic 1,3-oxathiolanes 6 and 7 bearing the Ph group at C(3) (Scheme 3). The structures of 3, 4, 6, and 7 were confirmed by X-ray crystallography (Figs. 1 and 2). These results show that oxiranes react selectively with the thiocarbonyl group (CS) in 1. Furthermore, the nucleophilic attack of the thiocarbonyl S-atom at the SiO₂-activated oxirane ring proceeds with high regio- and stereoselectivity via an S_N2-type mechanism.     

Carbanucleosides: synthesis of both enantiomers of 2-(6-chloro-purin-9-yl)-3,5-bishydroxymethyl cyclopentanol from d-glucose

The key intermediate 1,2:5,6-di-O-isopropylidene-3-deoxy-3β-allyl-α-d-glucofuranose (8) could be conveniently prepared through radical induced allyl substitution at C-3 of appropriate 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose derivatives (7a,b) and used to synthesize enantiomeric bishydroxymethyl aminocyclopentanols 13 and 19 by the application of a 1,3-dipolar nitrone cycloaddition reaction involving the C-5 or C-1 aldehyde functionality. The products were subsequently transformed into carbanucleoside enantiomers 15 and 21. The diastereomeric isoxazolidinocyclopentane derivative 20 was similarly converted to carbanucleoside 22.     

Synthesis of water-soluble 2-alkylcyclodextrin-C60 conjugates and their inclusion complexation in aqueous solution

Two β-cyclodextrin-C₆₀ conjugates (3 and 4) with a flexible linker at the secondary face of cyclodextrin are synthesized by a single reaction of 2-(ω-azidoundecanyl)-2-O-heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin (2) and C₆₀, both of which display satisfactory water solubility. Structural analyses show that 3 is a closed [5,6] aziridinofullerene, whereas 4 is a bis-adduct derivative. Using rhodamine B (RhB) as a guest molecule, the inclusion complexation behavior of 3 was investigated in aqueous solution.     

The microbiological transformation of steroidal saponins by Curvularia lunata

The microbiological transformation of polyphyllin I (compound I), polyphyllin III (compound II), polyphyllin V (compound III) and polyphyllin VI (compound IV) by Curvularia lunata into their corresponding subsaponins, for example, diosgenin-3-O-α-l-arabinofuranosyl (1→4)-β-d-glucopyranoside (compound V), diosgenin-3-O-α-l-rhamnopyranosyl (1→4)-β-d-glucopyranoside (compound VI), diosgenin-3-O-β-d-glucopyranoside (compound VII) and pennogenin-3-O-β-d-glucopyranoside (compound VIII), were studied in this paper. Curvularia lunata is able to hydrolyze terminal rhamnosyls that are linked by 1→2 C- bond to sugar residues of steroidal saponins at C-3 position with high activity and regioselectivity.     

An efficient microwave assisted synthesis of novel class of Rhodanine derivatives as potential HIV-1 and JSP-1 inhibitors

(Z)-5-(2-(1H-Indol-3-yl)-2-oxoethylidene)-3-phenyl-2-thioxothiazolidin-4-one (7a-q) derivatives have been synthesized by the condensation reaction of 3-phenyl-2-thioxothiazolidin-4-ones (3a-h) with suitably substituted 2-(1H-indol-3-yl)-2-oxoacetaldehyde (6a-d) under microwave condition. The thioxothiazolidine-4-ones were prepared from the corresponding aromatic amines (1a-e) and di-(carboxymethyl)-trithiocarbonyl (2). The aldehydes (6a-h) were synthesized from the corresponding acid chlorides (5a-d) using HSnBu₃.     

Phase transitions in K3AlF6

Phase transitions in the elpasolite-type K₃AlF₆ complex fluoride were investigated using differential scanning calorimetry, electron diffraction and X-ray powder diffraction. Three phase transitions were identified with critical temperatures , and . The α-K₃AlF₆ phase is stable below T₁ and crystallizes in a monoclinic unit cell with a=18.8588(2)Å, b=34.0278(2)Å, c=18.9231(1)Å, β=90.453(1)° (a=2a_c−c_c, b=4b_c, c=a_c+2c_c; a_c, b_c, c_c—the basic lattice vectors of the face-centered cubic elpasolite structure) and space group I2/a or Ia. The intermediate β phase exists only in very narrow temperature interval between T₁ and T₂. The γ polymorph is stable in the T₂<T<T₃ temperature range and has an orthorhombic unit cell with a=36.1229(6)Å, b=17.1114(3)Å, c=12.0502(3)Å (a=3a_c−3c_c, b=2b_c, c=a_c+c_c) at 250 °C and space group Fddd. Above T₃ the cubic δ polymorph forms with a_c=8.5786(4)Å at 400 °C and space group . The similarity between the K₃AlF₆ and K₃MoO₃F₃ compounds is discussed.     

Biotransformation of triptolide by Cunninghamella blakesleana

Biotransformation of triptolide 1 by Cunninghamella blakesleana (AS 3.970) was carried out. Seven biotransformation products were obtained and four of them were characterized as new compounds. On the basis of their NMR and mass spectral data, their structures were characterized as 5α-hydroxytriptolide 2, 1β-hydroxytriptolide 3, triptodiolide 4, 16-hydroxytriptolide 5, triptolidenol 6, 19α-hydroxytriptolide 7 and 19β-hydroxytriptolide 8. All the new transformed products (2, 3, 7 and 8) were found to exhibit potent in vitro cytotoxicity against some human tumor cell lines.     

Unusual formation of β-carboline dimers under Bischler-Napieralski reaction conditions: an old reaction with a new direction

l-N-Formyl tryptophan methyl ester (3) underwent a Bischler-Napieralski reaction with POCl₃ at room temperature or under microwave irradiation, resulting in the unusual formation of β-carboline dimers 5 and 6. Most importantly, acetylation using Ac₂O of each of the dimers 5 and 6 separately afforded 1-[3′-carbomethoxy-β-carbolinyl]-3-carbomethoxy-9-acetyl-β-carboline (7) as the only product, the structure of which was confirmed by X-ray crystallography studies.     

Biotransformation of two stemodane diterpenes by Mucor plumbeus

The microbiological transformation of 13α,17-dihydroxy-stemodane (2) by the fungus Mucor plumbeus afforded 13α,17,19-trihydroxy-stemodane (3), 3β,13α,17-trihydroxy-stemodane (5), 3-oxo-13α,17-dihydroxy-stemodane (7), 7α,13α,17,19-tetrahydroxy-stemodane (8), 3β,11α,13α,17-tetrahydroxy-stemodane (10), 3β,7α,13α,17-tetrahydroxy-stemodane (12), 3β,8β,13α,17-tetrahydroxy-stemodane (14), 2α,13α,17-trihydroxy-stemodane (16), 2α,13α,17,19-tetrahydroxy-stemodane (17), 2α,3β,13α,17-tetrahydroxy-stemodane (20) and 3β,11β,13α,17-tetrahydroxy-stemodane (22), whilst the incubation of 13α,14-dihydroxy-stemodane (25) gave 3β,13α,14-trihydroxy-stemodane (28), 2α,13α,14-trihydroxy-stemodane (29) and 13α,14,19-trihydroxy-stemodane (30). Preference for hydroxylations of ring A at C-2(α), C-3(β) and C-19 were observed in both incubations. An interesting rearrangement of 13α,14α-dihydroxy-stemodanes to 14-oxo derivatives with an unusual carbon framework has been observed under acetylation conditions. We have named this skeleton prestemodane, which, as a hydrocarbon ion, had been postulated as a biogenetic precursor of stemodane.     

Synthesis, crystal structure, infrared and Raman spectra of Sr4Cu3(AsO4)2(AsO3OH)4·3H2O and Ba2Cu4(AsO4)2(AsO3OH)3

The two new compounds, Sr₄Cu₃(AsO₄)₂(AsO₃OH)₄·3H₂O (1) and Ba₂Cu₄(AsO₄)₂(AsO₃OH)₃(2), were synthesized under hydrothermal conditions. They represent previously unknown structure types and are the first compounds synthesized in the systems SrO/BaO-CuO-As₂O₅-H₂O. Their crystal structures were determined by single-crystal X-ray diffraction [space group C2/c, a=18.536(4) Å, b=5.179(1) Å, c=24.898(5) Å, β=93.67(3)°, V=2344.0(8) Å³, Z=4 for 1; space group P4₂/n, a=7.775(1) Å, c=13.698(3) Å, V=828.1(2) Å³, Z=2 for 2]. The crystal structure of 1 is related to a group of compounds formed by Cu²⁺-(XO₄)³⁻ layers (X=P⁵⁺, As⁵⁺) linked by M cations (M=alkali, alkaline earth, Pb²⁺, or Ag⁺) and partly by hydrogen bonds. In 1, worth mentioning is the very short hydrogen bond length, D···A=2.477(3) Å. It is one of the examples of extremely short hydrogen bonds, where the donor and acceptor are crystallographically different. Compound 2 represents a layered structure consisting of Cu₂O₈ centrosymmetric dimers crosslinked by As1φ₄ tetrahedra, where φ is O or OH, which are interconnected by Ba, As2 and hydrogen bonds to form a three-dimensional network. The layers are formed by Cu₂O₈ centrosymmetric dimers of CuO₅ edge-sharing polyhedra, crosslinked by As1O₄ tetrahedra. Vibrational spectra (FTIR and Raman) of both compounds are described. The spectroscopic manifestation of the very short hydrogen bond in 1, and ABC-like spectra in 2 were discussed.     

Supramolecular nanostructured assemblies of different types of porphyrins with fullerene using TiO2 nanoparticles for light energy conversion

TiO₂ nanoparticles were modified with porphyrin derivatives, 5-[4-benzoic acid]-10,15,20-tris[3,5-di-tert-butylphenyl]-21H,23H-porphyrin (Ar-H₂P-COOH), 5-[4-benzoic acid]-10,20-tris[3,5-di-tert-butylphenyl]-21H,23H-porphyrin (H-H₂P-COOH), and 5,10,15,20-tetra[4-benzoic acid]-21H,23H-porphyrin (H₂P-4COOH). The porphyrin-modified TiO₂ nanoparticles were deposited on nanostructured OTE/SnO₂ electrode together with nanoclusters of fullerene (C₆₀) in acetonitrile-toluene (3/1, v/v) using an electrophoretic deposition technique to afford the porphyrin-modified TiO₂ composite electrode denoted as OTE/SnO₂/(porphyrin-modified TiO₂ nanoparticle+C₆₀)_n. The porphyrin-modified TiO₂ composite electrodes have efficient light absorbing properties in the visible region, exhibiting the photoactive response under visible light excitation using redox couple. The incident photon-to-photocurrent efficiency (IPCE) values of supramolecular nanostructured electrodes of porphyrin-modified TiO₂ nanoparticles with fullerene [OTE/SnO₂/(Ar-H₂P-COO-TiO₂+C₆₀)_n, OTE/SnO₂/(H-H₂P-COO-TiO₂+C₆₀)_n, and OTE/SnO₂/(H₂P-4COO-TiO₂+C₆₀)_n] are much larger than those of the reference systems of porphyrin-modified TiO₂ nanoparticles without C₆₀ [OTE/SnO₂/(Ar-H₂P-COO-TiO₂)_n, OTE/SnO₂/(H-H₂P-COO-TiO₂)_n, and OTE/SnO₂/(H₂P-4COO-TiO₂)_n]. In particular, the maximum IPCE value (41%) is obtained for OTE/SnO₂/(H-H₂P-COO-TiO₂+C₆₀)_n under the bias potential of 0.2 V versus SCE. This indicates that the formation of supramolecular complexes between porphyrins and fullerene on TiO₂ nanoparticles plays an important role in improvement of the light energy conversion properties.     

On the microstructure and symmetry of apparently hexagonal BaAl2O4

The P6₃ (a=2a_p, b=2b_p, c=c_p) crystal structure reported for BaAl₂O₄ at room temperature has been carefully re-investigated by a combined transmission electron microscopy and neutron powder diffraction study. It is shown that the poor fit of this P6₃ (a=2a_p, b=2b_p, c=c_p) structure model for BaAl₂O₄ to neutron powder diffraction data is primarily due to the failure to take into account coherent scattering between different domains related by enantiomorphic twinning of the P6₃22 parent sub-structure. Fast Fourier transformation of [0 0 1] lattice images from small localized real space regions (∼10 nm in diameter) are used to show that the P6₃ (a=2a_p, b=2b_p, c=c_p) crystal structure reported for BaAl₂O₄ is not correct on the local scale. The correct local symmetry of the very small nano-domains is most likely orthorhombic or monoclinic.     

Reactivity of the dinuclear platina-β-diketone [Pt2{(COMe)2H}2(μ-Cl)2] towards chelating ligands - Bridge cleavage versus formation of acetyl(chloro)platinum(II) complexes

The dinuclear platina-β-diketone [Pt₂{(COMe)₂H}₂(μ-Cl)₂] (1) was found to react with 2-(ROCH₂)C₅H₄N (R =  Me, 2a; H, 2b) yielding a cationic mononuclear platina-β-diketone [Pt{(COMe)₂H}{2-(MeOCH₂)C₅H₄N}]Cl (3) and an acetyl(chloro)platinum(II) complex [Pt(COMe)Cl{2-(HOCH₂)C₅H₄N}] (4), respectively. The reaction of 1 with 8-(methylthio)quinoline (5) resulted in the formation of [Pt(COMe)Cl{8-(MeS)C₉H₆N}] (6). The identities of all complexes were established by microanalysis, ¹H, and ¹³C NMR spectroscopy. Single-crystal X-ray diffraction analysis showed 6 to be square-planar platinum(II) complex with N and C atoms as well as Cl and S atoms in mutually trans positions (configuration index: SP-4-2). In accordance with this, quantum chemical calculations on the DFT level of theory revealed a higher stability of complex 6 having a SP-4-2 configuration vs. the analogous complex in SP-4-3 configuration. The distinctly different reactivity of 1 with 2a on the one hand and with 2b and 5 on the other is discussed in terms of the HSAB concept and a deprotonation/reprotonation reaction.     

Total synthesis of (±)-camphorataimides and (±)-himanimides by NaBH4/Ni(OAc)2 or Zn/AcOH stereoselective reduction

Maleic anhydride 1 of Antrodia camphorate, which can be isolated from Chinese herbal medicine, is achieved in which the longest linear sequence is only five steps, in 40% overall yield from commercially available succinic anhydride. The crucial antrodimides 3 and 2 can be readily transformed by the chemoselective reduction with Zn/AcOH and NaBH₄/Ni(OAc)₂·4H₂O to afford the naturally occurring camphorataimides, 4 and 5, in high yields as well, respectively. This synthetic strategy can also be modified to give access to a variety of different maleic acid derivatives, himanimides 6-8.     

A new route for the preparation of the 22,23-dioxocholestane side chain from diosgenin and its application to the stereocontrolled construction of the 22R,23S-diol function

The new (22R,23S,25R)-3β,16β,26-triacetoxy-cholest-5-ene-22,23-diol (11a) was synthesized from diosgenin (3) through a synthetic route based on chemoselective RuO₄ oxidation of (25R)-3β,16β-diacetoxy-23-ethyl-23¹,26-epoxycholesta-5,23(23¹)-dien-22-one (9) that afforded (20S,25R)-3β,16β,26-triacetoxycholest-5-ene-22,23-dione (10) which was stereoselectively reduced using NaBH₄. Compound 9 was obtained from the known isomeric 22,26-epoxycholest-5-ene steroidal skeleton 8b by treatment with p-TsOH in toluene, amberlyst-15 or directly from diosgenin by treatment with BF₃·OEt₂/Ac₂O. Chemoselective reduction of the 23-keto group of 10, was attained using NaBH₄/ZnCl₂ at −70 °C to give 23S-14. The NMR spectra of all compounds were unambiguously assigned based on one and two dimensional experiments and the C-22 and C-23 stereochemistry in the diacetate derivative 11b, as well as the structure of epoxycholestene 9 were further established by X-ray diffraction analyses. The new route for the functionalization of the side chain of diosgenin can find application in the synthesis of norbrassinosteroid analogues.