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.     

A convergent total synthesis of antiplasmodial C2 symmetric (+)-ekeberin D4

The first concise total synthesis of C₂ symmetric (+)-ekeberin D₄ (1) that exhibits antiplasmodial activity has been achieved in total nine steps and 27% yield from the known diol 4. The efficient synthetic method features the regio- and diastereoselective epoxidation of 4 and convergent coupling between half fragments 2 and 3 by taking into account the C₂ symmetric property.     

Chiral N-phosphonyl imine chemistry: new reagents and their applications for asymmetric reactions

Novel chiral N-phosphonyl imines 2 have been designed and synthesized using chiral N-phosphoramide 1. These N-phosphonyl imines have been successfully utilized for asymmetric aza-Darzens reaction and asymmetric aza-Henry reaction. The C₂-symmetric chiral auxiliary tolerates oxidation, is not sensitive to racemization and can be recycled for large scale synthesis.     

Carbonylation studies of Pd-methyl complexes modified with 1,4-Cs-symmetrical diphosphine ligands

Neutral palladium methyl chloride 2a-d [PdCH₃(PˆP′)Cl] and cationic palladium methyl acetonitrile mono-triflate 3a-d [PdCH₃(PˆP′)(CH₃CN)](CF₃SO₃) complexes were synthesized and fully characterized (PˆP′ = 1a-d). All the neutral and cationic complexes containing a C_s-symmetric diphosphine exist in solution as a mixture of geometric isomers. The carbonylation at atmospheric pressure of the neutral and cationic complexes revealed that migratory insertion of carbon monoxide is not stereospecific in these systems. The neutral and cationic acyl complexes were formed in situ as mixtures of stereoisomers, which were characterized by means of NMR spectroscopy.The crystal structures of [Pd(1a)Cl]₂(OTf)₂ and 2d are described.     

Olefin insertion in Pd-acyl complexes modified with 1,4-Cs-symmetrical diphosphine ligands

The insertion of ethene and propene was investigated in palladium(II) acyl complexes of the type [PdC(O)CH₃(P^∧P′)(CH₃CN)](OTf) modified with the C_s-symmetric diphosphines 2-4 and the parent ligand 1, described by C_2v-symmetry and taken as a reference.Ethene insertion was investigated for acyl complexes containing the ligands 2 and 3. Two insertion products formed in a ratio of approximately 1:1 for both systems, irrespective of the electronic properties of the ligands.Propene as an α-olefin can insert according to a 1,2- or 2,1-insertion mode into a palladium acyl bond, arising regioselectivity issues. Moreover, due to the C_s-symmetry of the ligands, two stereoisomers can result upon insertion, as the alkyl group of the formed five-membered metallacycle can be cis or trans to each non-equivalent moiety. Propene insertion was indeed neither stereo- nor regioselective in the cases of 3 and 4, in which the products arising from both 1,2- and 2,1-insertion were observed. 2 displayed total control of stereo- and regioselectivity, with the formation of one primary insertion product. Similar regioselectivity was observed for the reference ligand 1. The regioisomeric distribution was different from equimolar for propene insertion, where the ratio of the products might be controlled by a combination of steric and electronic factors.     

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.     

Michael addition of chiral formaldehyde N,N-dialkylhydrazones to activated cyclic alkenes

The nucleophilic conjugate addition of chiral formaldehyde N,N-dialkylhydrazones 1 to doubly activated cyclic alkenes 2-8 proceeds smoothly to afford the corresponding Michael adducts 14, 16, 18, 20, 22, 24, and 25 in variable yields and selectivities. The reactions take place either spontaneously or in the presence of MgI₂ as a mild Lewis acid depending on the type of substrate. Release of the chiral auxiliary was achieved by transformation of the hydrazone moiety into acetals, dithioacetals or nitriles.     

A facile approach for the synthesis of novel substituted 4H-chromenes and condensation reactions of 4H-chromenes leading to chromenopyrrolones and triazolylchromenopyrrolones

A facile method has been developed for the synthesis of 4H-chromene-3-carboxylates 3a–d by the nucleophilic substitution reaction of 2-hydroxy-2H-chromene-3-carboxylates 2a–d with triethylsilane in the presence of BF₃·O(C₂H₅)₂. Cyclocondensation of 4H-chromene-3-carboxylates 3a–d with benzylamines 4a–d afforded a series of 2,3-dihydrochromenopyrrolones 5a–p and with propargylamine afforded 2-propynyl-2,3-dihydrochromenopyrrolones 6a–d. Click reaction of 6a–d with benzyl azides 7a–d provided a series of 1H-1,2,3-triazolylmethyl-2,3-dihydrochromenopyrrolones 8a–p. Thus synthesized compounds 3a–d, 5a–p, 6a–d, and 8a–p are novel heterocyclic compounds and being reported for the first time.     

Lyconadins C and F, new Lycopodium alkaloids from Lycopodium complanatum

New Lycopodium alkaloids, lyconadins C (1) and F (2), were isolated from the club moss Lycopodium complanatum. Lyconadin C (1) is a new C₁₆N₂-type Lycopodium alkaloid possessing unique fused-tetracyclic ring system consisting of a cycloheptene ring fused to a decahydroquinoline and pyridone rings. Lyconadin F (2) possesses a primary amide moiety in its molecular, which is the first example of Lycopodium alkaloids. Biogenetically, lyconadins C (1) and F (2) might be related to lyconadins A (4) and B (5). The structures and relative stereochemistry of 1 and 2 were elucidated on the basis of spectroscopic data. The absolute stereochemistry of 2 was elucidated by chemical correlations with lyconadin B (5) through hemiaminal form of lyconadin F (3).     

Synthesis, characterization and crystal structures of cyclometallated palladium (II) compounds containing difunctional ligands with [P,P], [As,As], [N,N], [P,As], [P,N] and [P,O] donor atoms

Treatment of the chloro-bridged dinuclear complex [Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}(μ-Cl)]₂ (1) with homobidentate [P,P], [As,As], [N,N], and heterobidentate [P,As], [P,N] ligands in a 1:1 molar ratio gave the dinuclear complexes [{Pd[3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N](Cl)}₂{μ-L}] (L = Ph₂PC₄H₆(NH)CH₂PPh₂ (2); Ph₂As(CH₂)₂AsPh₂ (3); 1,3-(NH₂CH₂)₂C₆H₄ (4); Ph₂P(CH₂)₂AsPh₂ (5); Ph₂P(CH₂)₂NH₂ (6)), with the bidentate ligands bridging the two cyclometallated fragments.The reaction with the homobidentate ligands in a 1:2 molar ratio in the presence of NaClO₄ afforded the mononuclear compounds [[Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}{L-P,P}][ClO₄] (L = Ph₂PC₄H₆(NH)CH₂PPh₂ (7); (o-Tol)₂P(CH₂)₂P(o-Tol)₂ (8)), [Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}{Ph₂As(CH₂)₂AsPh₂-As,As}][ClO₄] (9) and [Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}{L-N,N}][ClO₄] (L = NH₂(CH₂)₃NH₂ (10); NH₂(C₆H₈)CH₂(C₆H₈)NH₂ (11); 1,3-(NH₂CH₂)₂C₆H₄ (12); 1,3-(NH₂)₂C₅H₃N (13); NH₂(C₆H₄)O(C₆H₄)NH₂ (14); NMe₂(CH₂)₂NMe₂ (15)), in which the chloro ligands are absent and the bidentate ligands are chelated to the palladium atom.Reaction of 1 with Ph₂P(CH₂)₂AsPh₂ in 1:2 molar ratio in acetone in the presence of NH₄PF₆ afforded the analogous mononuclear compound [Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}{Ph₂P(CH₂)₂AsPh₂-P,As}][PF₆] (16); whereas reaction with Ph₂P(CH₂)₃NH₂ gave [Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}{Ph₂P(CH₂)₃N(CMe₂)-P,N}][PF₆] (17), derived from intermolecular condensation between the aminophosphine and acetone. Condensation of the NH₂ group was precluded by change of solvent, using dichloromethane.Iminophoshines also reacted with 1 in 1:2 molar ratio in acetone to give a new series of mononuclear cyclometallated complexes: [Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}{L-P,N}][ClO₄] (L = Ph₂PC₆H₄C(H)NCy (20); Ph₂PC₆H₄C(H)NC(CH₃)₃ (21); Ph₂PC₆H₄C(H)NNMe₂ (22); Ph₂PC₆H₄C(H)NNHMe (23); Ph₂PC₆H₄C(H)NNHPh (24)). Analogous complexes with a stable P,O-chelate were obtained using bidentate [P,O] donor ligands: [Pd{3,4-(MeO)₂C₆H₂C(H)N(Cy)-C6,N}{L-P,O}][Cl] (L = 2-(Ph₂P)C₆H₄CHO (25); Ph₂PN(Me)C(O)Me (26)).The crystal structures of compounds 1, 5, 15, 16, 18, 20 have been determined by X-ray crystallography.     

Stereocontrolled synthesis of imidazolo[1,5]hexopiperidinoses and imidazol-4(5)-yl-C-glycosides

The syntheses of imidazolo[1,5]hexopiperidinoses 2-6 and imidazol-4(5)-yl C-glycosides 7-9 are reported. The crucial step of this approach relies upon the S_N2-type cyclisation of selectively protected C(1), C(2), C(3) and C(5)-substituted 1-[imidazol-4(5)-yl]pentitols in which the imidazole nitrogen or the C(1)-connected oxygen are involved as the competitive nucleophilic centers, respectively. Six selected imidazolosugars were evaluated as potential inhibitors of glycosidases.     

Novel C1-symmetric chiral crown ethers bearing rosin acids groups: synthesis and enantiomeric recognition for ammonium salts

Four types of novel C₁-symmetric chiral crown ethers including 28-crown-8, 20-crown-6, 17-crown-5 and 14-crown-3 (9a–m) were synthesized and their enantiodiscriminating abilities with protonated primary amines (10–14) were examined by ¹H NMR spectroscopy. 20-crown-6 crown ethers exhibited good chiral recognition properties toward these guests and showed different complementarity to some chiral guests, indicating that 20-crown-6 crown ethers could be used as a chiral NMR solvating agent to determine the enantiopurity of these guests. In addition, the binding model and binding site between the hosts and guests were also studied by the computational modeling and experimental calculation.     

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.     

Highly stereoselective addition of organozinc reagents to pentopyranose derived glycals: effect of protecting group and assignment of C-glycoside stereochemistry

The nucleophilic addition of ethyl 3-propionylzinc iodide to a variety of differently protected pentopyranose derived d-glycals 6a-g proceeds with good to high levels of diastereoselectivity to provide the corresponding β-C-glycosides 7. The stereochemistry of the para-nitrobenzoate derivative 7d has been confirmed by X-ray crystallography, and the stereochemistry of the other β-C-glycoside products has been correlated to 7d. The stereochemical outcome observed supports the earlier suggestion by Isobe that through-space effects are important in stabilising and controlling the reactivity of the intermediate oxonium species represented by 11.     

Rhodium(I) complexes with κP coordinated ω-phosphinofunctionalized alkyl phenyl sulfide, sulfoxide and sulfone ligands and their reactions with sodium bis(trimethylsilyl)amide and Ag[BF4]

Reactions of ω-diphenylphosphinofunctionalized alkyl phenyl sulfides Ph₂P(CH₂)_nSPh (n = 1, 1a; 2, 2a; 3, 3a), sulfoxides Ph₂P(CH₂)_nS(O)Ph (n = 1, 1b; 2, 2b; 3, 3b) and sulfones Ph₂P(CH₂)_nS(O)₂Ph (n = 1, 1c; 2, 2c; 3, 3c) with dinuclear chlorido bridged rhodium(I) complexes [(RhL₂)₂(μ-Cl)₂] (L₂ = cycloocta-1.5-diene, cod, 4; bis(diphenylphosphino)ethane, dppe, 5) afforded mononuclear Rh(I) complexes of the type [RhCl{Ph₂P(CH₂)_nS(O)_xPh-κP}(cod)]¹ (n/x = 1/0, 6a; 1/1, 6b; 1/2, 6c; 2/0, 8a; 2/1, 8b; 2/2, 8c; 3/0, 10a; 3/1, 10b; 3/2, 10c) and [RhCl{Ph₂P(CH₂)_nS(O)_xPh-κP}(dppe)] (n/x = 1/0, 7a; 1/1, 7b; 1/2, 7c; 2/0, 9a; 2/1, 9b; 2/2, 9c; 3/0, 11a; 3/1, 11b; 3/2, 11c) having the P^S(O)_x ligands κP coordinated. Addition of Ag[BF₄] to complexes 6-11 in CH₂Cl₂ led with precipitation of AgCl to cationic rhodium complexes of the type [Rh{Ph₂P(CH₂)_nS(O)_xPh-κP,κS/O}L₂][BF₄] having bound the P^S(O)_x ligands bidentately in a κP,κS (13a-18a, 15b-18b) or a κP,κO (13b, 14b, 13c-18c) coordination mode. Unexpectedly, the addition of Ag[BF₄] to 6a in THF afforded the trinuclear cationic rhodium(I) complex [Rh₃(μ-Cl)(μ-Ph₂PCH₂SPh-κP:κS)₄][BF₄]₂·4THF (12·4THF) with a four-membered Rh₃Cl ring as basic framework. Addition of sodium bis(trimethylsilyl)amide to complexes 6-11 led to a selective deprotonation of the carbon atom neighbored to the S(O)_x group (α-C) yielding three different types of organorhodium complexes: a) Organorhodium intramolecular coordination compounds of the type [Rh{CH{S(O)_xPh}CH₂CH₂PPh₂-κC,κP}L₂] (22a-c, 23a-c), b) zwitterionic complexes [Rh{Ph₂PCHS(O)_xPh-κP,κS/O}L₂] having κP,κS (21a, 21b) and κP,κO (20b/c, 21c) coordinated anionic [Ph₂PCHS(O)_xPh] ligands, and c) the dinuclear rhodium(I) complex [{Rh{μ-CH(SPh)PPh₂-κC:κP}(cod)}₂] (19). All complexes were fully characterized spectroscopically and complexes 15b, 15c, 12·4THF and 19·THF additionally by X-ray diffraction analysis. DFT calculations of zwitterionic complexes gave insight into the coordination mode of the [Ph₂PCHS(O)Ph] ligand (κP,κS versus κP,κO).     

Guignardins A–F,spirodioxynaphthalenes from the endophytic fungus Guignardia sp. KcF8 as a new class of PTP1B and SIRT1 inhibitors

Six new guignardins A–F (1–6) were isolated from the cultures of endophytic fungus Guignardia sp. KcF8 derived of a mangrove plant Kandelia candel, along with three known analogues, palmarumycins C₁ (7), BG1 (8), and JC1 (9). Compounds 2, 3, 7, and 8 showed antimicrobial activities. Compounds 5–7 exhibited significant cytotoxicities against 10 human tumor cell lines. Compound 3 also displayed significant inhibitory activity against human protein tyrosine phosphatase 1B and histone deacetylase silent information regulator T1enzymes, two key targets for the treatment of diabetes. This is the first report on the anti-PTP1B and anti-SIRT1 activities of spirodioxynaphthalenes.     

Lycopladines F and G, new C16N2-type alkaloids with an additional C4N unit from Lycopodium complanatum

Two new Lycopodium alkaloids, lycopladines F (1) and G (2), have been isolated from the club moss Lycopodium complanatum, and the structures and relative stereochemistries of 1 and 2 were elucidated on the basis of spectroscopic data. Lycopladine F (1) is a rare C₁₆N₂-type Lycopodium alkaloid possessing an amino acid residue (C₄N).     

Synthesis and characterisation of six Fe(II or III), Co(II) or Zr(IV) complexes containing the ligand [CH(SiMe2R)P(Ph)2NSiMe3] (R = Me, NEt2) and of [Co{N(SiMe3)C(Ph)C(H)P(Ph)2NSiMe3}2]

The C,N-(trimethylsilyliminodiphenylphosphoranyl)silylmethylmetal complexes [Fe(L)₂] (3), [Co(L)₂] (4), [ZrCl₃(L)]·0.83CH₂Cl₂ (5), [Fe(L)₃] (6), [Fe(L′)₂] (7) and [Co(L′)₂] (8) have been prepared from the lithium compound Li[CH(SiMe₂R)P(Ph)₂NSiMe₃] [1a, (R = Me) {≡ Li(L)}; 1b, (R = NEt₂) {≡ Li(L′)}] and the appropriate metal chloride (or for 7, FeCl₃). From Li[N(SiMe₃)C(Ph)C(H)P(Ph)₂NSiMe₃] [≡ Li(L″)] (2), prepared in situ from Li(L) (1a) and PhCN, and CoCl₂ there was obtained bis(3-trimethylsilylimino- diphenylphosphoranyl-2-phenyl-N-trimethylsilyl-1-azaallyl-N,N′)cobalt(II) (9). These crystalline complexes 3-9 were characterised by their mass spectra, microanalyses, high spin magnetic moments (not 5) and for 5 multinuclear NMR solution spectra. The X-ray structure of 3 showed it to be a pseudotetrahedral bis(chelate), the iron atom at the spiro junction.     

24,24-Dimethylvitamin D3-26,23-lactones and their 2α-functionalized analogues as highly potent VDR antagonists

Novel vitamin D receptor (VDR) antagonists, 24,24-dimethyl-1α-hydroxyvitamin D₃-26,23-lactones (8 and 9) and their C2α functionalized analogues (8a-c and 9a-c) were efficiently synthesized and their biological activities were evaluated. The construction of vitamin D₃ triene skeleton was achieved by palladium-catalyzed alkenylative cyclization of A-ring precursor enyne (22 and 22a-c) with CD-ring bromoolefin having a 24,24-dimethyl-α-methylene-γ-lactone unit on the side chain (13 and 14). The CD-ring precursors 13 and 14 were prepared by using chromium-mediated allylation of the aldehyde 10 derived from vitamin D₂. On the other hand, the A-ring enyne having 2α-(3-hydroxypropyl) group (22b) was newly synthesized from epoxide 15 using regio- and stereoselective alkylation methodology. The potency of the antagonistic activity of the newly designed analogues (8 and 9) increased up to 12 times that of TEI-9647 (2). Furthermore, introduction of the three motifs, that is, a methyl (8a and 9a), an ω-hydroxypropyl (8b and 9b) or an ω-hydroxypropoxyl group (8c and 9c) into the C2α position of 8 and 9, respectively, resulted in remarkable enhancement, up to 89 times, of the antagonistic activity on VDR.     

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.