Two New Diterpens Phenols-7α-Methoxydeoxocryptojaponol and 7β-Hydroxydeoxocryptojaponol

Six crystalline compounds, α-cedrol, β-sitosterol, cryptojaponol sugiol and two new diterpene phenols were isolated from the hexane extractive of wood of Juniperus formosana Hayata. Two new phenolic derivatives of deoxocryptojaponol were established as 7α-methoxydeoxocryptojaponol and 7β-hydroxydeoxocryptojaponol, respectively, by chemical and physical evidence.     

5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成

以5-雄烯二醇为原料,用微生物转化的方法合成了两个重要的神经甾体5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇。所用菌种总枝毛霉为我们自己筛选,并首次应用于5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成中。     

On the Reactivity of (−)‐(R)‐Carvone and (−)‐4aα,7α,7aβ‐Nepetalactone: Synthesis of New Heterocycles

The 1,3‐dipolar cycloaddition of 4‐chlorobenzonitrile oxide to the unsaturated system of (?)‐(R)‐carvone occurred exclusively at C(8) to give a new isoxazoline derivative. This derivative reacts with NH₂OH to yield a new heterocycle, observed for the first time. On the other hand, the addition of 4‐chlorobenzonitrile oxide to the unsaturated lactone (?)‐4aα,7α,7aβ‐nepetalactone gave, in a good yield, also a new heterocycle, again obtained for the first time. The terpenoid (?)‐(R)‐carvone and iridoid (?)‐4aα,7α,7aβ‐nepetalactone were isolated from Moroccan species Mentha viridis (L.) and Nepeta tuberosa (L.), respectively. The new heterocycles obtained were identified by combination of chromatographic and spectroscopic methods.     

21α‐Fluoro‐7‐norvouacapane‐17β,21α‐lactone

The crystal structure of 21α‐fluoro‐7‐norvouacapane‐17β,21α‐lactone, C₂₀H₂₅FO₃, a new synthetic derivative of the diterpenoid 6α,7β‐di­hydroxy­vouacapan‐17β‐oic acid isolated from Pterodon polygalaeflorus Benth fruits, is described.     

胆甾-4α-甲基-8-烯-3β，7α-二醇二乙酸酯的结构与性质研究

Lophenol, cholest-4α-methyl-7-en-3β-ol (1), obtained from Dracaena cochinchinensis (Lour.) S. C. Chen, was structurally modified. It was acetylated to protect 3β-hydroxyl group, and then oxidised by selenium dioxide in acetic acid to give cholest-4a-methyl-8-en-3β, Ta-diol diacetate (3). This compound 3 is unstable in chloroform solution or when heated and easily converted to a diene compound, cholest-4a-methyl-7,14-dien-3β-ol acetate (4). The structures of 3 and 4 were elucidated by means of IR, ^1H NMR, ^13C NMR and MS, and the absolute configuration of 3 was established by X-ray crystallography. The property of 3 was also discussed in this paper. Both 3 and 4 are new compounds and were reported for the first time.     

Umwandlung von Cardenoliden durch Mikroorganismen VI. 7β, 11α-Dihydroxydigitoxigenin und Abbau von 7β-Hydroxy-digitoxigenin zum 3β, 7β-Diacetoxy-14-hydroxy-5β, 14β, 17αH-ätiansäure-methylester. Mitteilung über Reaktionen mit Mikroorganismen [1]

Digitoxigenin ( 3 ) was transformed by a Fusarium spec. to 7β-hydroxydigitoxigenin ( 1 ) 1β, 7β-dihydroxydigitoxigenin ( 4 ) and to the hitherto unknown 7β, 11α-dihydroxydigitoxigenin ( 9 ). 7β-acetoxy-digitoxigenin ( 2 ) was degraded to methyl 3β, 7β-diacetoxy-14-hydroxy-5β, 14β, 17αH-etianate ( 11 ).     

Fluorescent Agonists of the α7 Nicotinic Acetylcholine Receptor Derived from 3‐Amino‐Quinuclidine

Here, we investigated whether fluorescence labeled small molecule agonists of the α7 nicotinic acetylcholine receptor (nAChR) might be identified to enhance receptor studies. Enantiomerically pure 3‐amino‐quinuclidines appended with fluorophores at the 3‐amino group were synthesized and tested by electrophysiology on human α7 nAChR in Xenopus oocytes, uncovering (R)‐ 4 and (R)‐ 9 as the first examples of fluorescent α7 nAChR agonists. These molecules elegantly incorporate the fluorescent reporter group as part of the pharmacophore itself and provide a new class of tool compounds for the study of these ligand‐gated ion channels.     

β‐K2Cr2O7

The monoclinic modification of dipotassium dichromate, β‐K₂Cr₂O₇, has been synthesized in the K₂Cr₂O₇–H₂O system. The structure consists of K⁺ cations and Cr₂O₇^2? dimers. In contrast with triclinic α‐K₂Cr₂O₇ [Kuz'min, Ilyukhin, Kharitonov & Belov (1969). Krist.Tech. 4 , 441–461], the Cr₂O₇^2? groups in β‐K₂Cr₂O₇ have twofold crystallographic symmetry and are parallel to each other.     

Substituted γ-lactones. XXX. Reactions of α-Keto-β-Subtituted-γ-butyrolactones with diamines

The condensation reaction between α-keto-β-aroyl (or acyl) -γ-butyrolactones, 4a-4e and o-phenylenediamine or 2, 3-diaminonaphthalene leads under retrograde aldol condensation involving loss of formaldehyde to formation of 3-substituted-3, 4-dihydro-2 (1H) quinoxalinones or benzo [g] quinoxalinones, 7a-7g , respectively as a new convenient synthesis of this type of heterocyclic systems. The reaction of type 4 compound with 4, 5-diaminopyromidine, 8 , was found to proceed differently. 2-[(4-Amino-5-pyrimidinyl)amine]-4-oxo-3-(hydroxymethyl)-4-phenyl-2-butenoic acid 9 was the only product formed when the reaction between 4a and 8 was run in ethanol. The same reaction in glacial acetic acid proceeds with loss of formaldehyde, to afford 7-phenacylidene-7,8-dihydro-6 (1H)-pteridione 10 . The reaction between type 4 compounds and ethylenediamine or 1, 4-phenylenediamine leads to the formation of the bis-condensation products 13–15 , respectively.     

Thermische Lactonisierung von Estern γ-Brom-α, β-ungesättigter Carbonsäuren zu Δα-Butenoliden. Direkte γ-Bromierung von α, β-ungesättigten Säuren

By heating with iron powder at 120–150° some γ-bromo-α, β-unsaturated carboxylic methyl esters, and, less smothly, the corresponding acids, were lactonized to Δ^7alpha;-butenolides with elimination of methyl bromide. The following conversions have thus been made: methyl γ-bromocrotonate ( 1c ) and the corresponding acid ( 1d ) to Δ^α-butenolide ( 8a ), methyl γ-bromotiglate ( 3c ) and the corresponding acid ( 3d ) to α-methyl-Δ^α-butenolide ( 8b ), a mixture of methyl trans- and cis-γ-bromosenecioate ( 7c and 7e ) and a mixture of the corresponding acids ( 7d and 7f ) to β-methyl-Δ^α-butenolide ( 8c ). The procedure did not work with methyl trans-γ-bromo-Δ^α-pentenoate ( 5c ) nor with its acid ( 5d ). Most of the γ-bromo-α, β-unsaturated carboxylic esters ( 1c, 7c, 7e and 5c ) are available by direct N-bromosuccinimide bromination of the α, β-unsaturated esters 1a, 7a and 5a ; methyl γ-bromotiglate ( 3c ) is obtained from both methyl tiglate ( 3a ) and methyl angelate ( 4a ), but has to be separated from a structural isomer. The γ-bromo-α, β-unsaturated esters are shown by NMR. to have the indicated configurations which are independent of the configuration of the α, β-unsaturated esters used; the bromination always leads to the more stable configuration, usually the one with the bromine-carrying carbon anti to the carboxylic ester group; an exception is methyl γ-bromo-senecioate, for which the two isomers (cis, 7e , and trans, 7d ) have about the same stability. The N-bromosuccinimide bromination of the α,β-unsaturated carboxylic acids 1b , 3b , 4b , 5b and 7b is shown to give results entirely analogous to those with the corresponding esters. In this way γ-bromocrotonic acid ( 1 d ), γ-bromotiglic acid ( 3 d ), trans- and cis-γ-bromosenecioic acid ( 7d and 7f ) as well as trans-γ-bromo-Δ^α-pentenoic acid ( 5d ) have been prepared. Iron powder seems to catalyze the lactonization by facilitating both the elimination of methyl bromide (or, less smoothly, hydrogen bromide) and the rotation about the double bond. α-Methyl-Δ^α-butenolide ( 8b ) was converted to 1-benzyl-( 9a ), 1-cyclohexyl-( 9b ), and 1-(4′-picoly1)-3-methyl-Δ^α-pyrrolin-2-one ( 9 c ) by heating at 180° with benzylamine, cyclohexylamine, and 4-picolylamine. The butenolide 8b showed cytostatic and even cytocidal activity; in preliminary tests, no carcinogenicity was observed. Both 8b and 9c exhibited little toxicity.     

Photochemische Reaktionen. 68. Mitteilung. Die Photoisomerisierung von α,β-ungesättigten γ,δ-Epoxyketonen: 9α, 10α- und 9β, 10β-Oxido-3-oxo-17β-acetoxy-Δ4-östren

Irradiation in the n→π* absorption band of the α,β-unsaturated γ,δ-epoxyketone 5 in ethanol at ?65° exclusively afforded the rearranged ene-dione 13 , whereas at + 24° under otherwise unchanged reaction conditions or upon triplet sensitization with Michler's ketone and with acetophenone at + 24° essentially identical mixtures of 13 (major product), 14 , and 15 were obtained. Selective π→π* excitation of 5 at ?78° and + 24° led to similar product patterns. The 9β,10β-epimeric epoxyketone 7 selectively isomerized to 14 and 15 at + 24° and n → π* or π → π* excitation. Neither the epoxyketones 5 and 7 nor the photoproducts 13–15 were photochemically interconverted. In separate photolyses each of the latter gave the double bond isomers 16 , 18 , and 19 , respectively. Cleavage of 13 to the dienone aldehyde 17 competed with the double bond shift ( → 16 ) when photolyzed in alcoholic solvents instead of benzene. The selective transformations 5 → 13 (at ?65° and n → π* excitation) and 7 → 14 + 15 are attributed to stereoelectronic factors facilitating the skeletal rearrangements of the diradicals 53 and 55 , the likely primary photoproducts resulting from epoxide cleavage in the triplet-excited compounds 5 and 7 , via the transition states 54 , 56 , and 57 . The loss of selectivity in product formation from 5 at higher temperature and n → π* excitation or triplet sensitization is explicable in terms of radical dissociation into 58 and 59 increasingly participating at the secondary thermal transformations of 53 . The similar effect of π → π* excitation even at ?78° indicates that some of the π,π* singlet energy may become available as thermal activation energy. It is further suggested that the considerably lesser ring strain in 14 and 15 , as compared with 13 , is responsible that selectivity in product formation from 7 is maintained also at +24° and at π → π* excitation.     

Unprecedented μ-η2:η2-Pyrazolate Coordination in [{Yb(η2-tBu2pz)(μ-η2:η2-tBu2pz)(thf)}2]

A higher degree of coordination saturation is attainable through the unusual coordination mode in the title compound 1 , in which the central pyrazolate groups function both as chelating and as bridging ligands. There is some asymmetry in the bridging, and the N atoms of each μ-η²:η²-pyrazolato ligand are 0.07–0.11 Å closer to one of the two Yb centers.     

Umwandlung von Krötengiften (Bufadienoldien) durch Mikroorganismen IV. 7β-Hydroxybufalin, 7β-Hydroxyresibufogenin und 12α-Hydroxyresibufogenin. 16. Mitteilung über Reaktionen mit Mikroorganismen [1]

Bufalin ( 1 ) was transformed to 7β-hydroxybufalin ( 2 ) by an aqueous suspension of the mycelium of Absidia orchidis VUILL. (HAGEM. ). Incubation of resibuforgenin ( 9 ) under the same conditions yielded 12α-hydroxyresibufogenin ( 7 ) and, under changed conditions, another monohydroxylated derivative which possesses most likely the structure of 7β-hydroxyresibufogenin ( 10 ). The corresponding cardenolide 3-O-acetyl-14β, 15β-epoxy-14-anhydro-digitoxigenin ( 17 ) gave both the 7β- and the 12α-monohydroxylated derivatives 18 and 22 and another monohydroxylated product 21 of unknown structure. All microbial transformation products are new.     

The synthesis of some complexed ketones or sulfones by oxidation of η-arene-η-cyclopentadienyliron cations or η-arenedi-η-cyclopentadienyliron dications

Di-η⁵-cyclopentadienyliron complexed dications of 9,10-dihydroanthracene, xanthene, thioxanthene and diphenylmethane derived from ligand exchange reactions but without their prior isolation were oxidized with KMnO₄ to give, respectively, the dications of anthraquinone, xanthone, thioxanthone and benzophenone, isolated as their dihexafluorophosphate salts. Cyclopentadienyliron complexes of arenes containing a sulfide function were oxidized by m-chloroperbenzoic acid to the corresponding complexed sulfones, and sulfones prepared in this way include the hexafluorophosphate salt of the η⁶-p-tolysulfonylbenzene, thioxanthene-10,10-dioxide, 9,9-dimethylthioxanthene-10,10-dioxide or dibenzothiophene-9,9-dioxide-η⁵-cyclopentadienyliron cation.     

Synthesis and Antitumor Activity Evaluation of γ-Monofluorinated and γ,γ-Difluorinated Goniothalamin Analogues

A series of novel γ,γ‐difluorinated Goniothalamin analogues 4a – 4i and 6a – 6i were synthesized. The key steps included the construction of C‐5 stereocenter adjacent to gem‐difluoromethylene group by way of lipase AK catalyzed kinetic resolution, the introduction of aryl group via Stille coupling, and lactonization by 1,5‐oxidative cyclization. These γ,γ‐difluorinated Goniothalamin analogues 4a – 4i and their enantiomers 6a – 6i , together with several corresponding γ‐monofluorinated Goniothalamin analogues were biologically evaluated against four different cancer cell lines. Compound 7h showed a nearly equivalent potency as the parent (R)‐Goniothalamin in the micromolar range. The different fluorine effects between fluoromethylene and gem‐difluoromethylene on antitumor activity were discussed through the analysis of bioassay data.     

3β,7α,12α‐Tri­formyl­oxy‐24‐nor‐5β‐chol‐22‐ene

The title compound, alternatively called 24‐nor‐5β‐chol‐22‐ene‐3β,7α,12α‐triyl triformate, C₂₆H₃₈O₆, has a cis junction between two of the six‐membered rings. All three of the six‐membered rings have chair conformations that are slightly flattened and the five‐membered ring has a 13β,14α‐half‐chair conformation. The 3β, 7α and 12α ring substituents are axial and the 17β group is equatorial. The 3β‐formyl­oxy group is involved in one weak intermol­ecular C—H⋯O bond, which links the mol­ecules into dimers in a head‐to‐head fashion.     

γ,δ‐ and δ,ε‐Unsaturated Aldehydes from γ‐ and δ‐Lactones in One Step. Preliminary Communication

A one‐step transformation of γ‐ and δ‐(spiro)lactones into γ,δ‐ and δ,ε‐unsaturated aldehydes with an excess of formic acid in the vapor phase over a supported manganese catalyst is described for the first time. The scope and limitations of this new reaction are shown with different lactones as substrate, and a mechanistic rationale is proposed.     

Reactivity Studies of η5‐ Indenyl and η5‐Cp* Ruthenium(II) Complexes towards some Polypyridyl Ligands

The reaction of [(η⁵‐L³)Ru(PPh₃)₂Cl], where; L³ = C₉H₇ ( 1 ), C₅Me₅ (Cp*) ( 2 ) with acetonitrile in the presence of [NH₄][PF₆] yielded cationic complexes [(η⁵‐L³)Ru(PPh₃)₂(CH₃CN)][PF₆]; L³= C₉H₇ ([3]PF₆) and L³ = C₅Me₅ ([4]PF₆), respectively. Complexes [3]PF₆ and [4]PF₆ reacts with some polypyridyl ligands viz, 2,3‐bis (α‐pyridyl) pyrazine (bpp), 2,3‐bis (α‐pyridyl) quinoxaline (bpq) yielding the complexes of the formulation [(η⁵‐L³)Ru(PPh₃)(L²)]PF₆ where; L³ = C₉H₇, L² = bpp, ([5]PF₆), L³ = C₉H₇, L² = bpq, ([6]PF₆); L³ = C₅Me₅, L² = bpp, ([7]PF₆) and bpq, ([8]PF₆), respectively. However reaction of [(η⁵‐C₉H₇)Ru(PPh₃)₂(CH₃CN)][PF₆] ([3]PF₆) with the sterically demanding polypyridyl ligands, viz. 2,4,6‐tris(2‐pyridyl)‐1,3,5‐triazine (tptz) or tetra‐2‐pyridyl‐1,4‐pyrazine (tppz) leads to the formation of unexpected complexes [Ru(PPh₃)₂(L²)(CH₃CN)][PF₆]₂; L² = tppz ([9](PF₆)₂), tptz ([11](PF₆)₂) and [Ru(PPh₃)₂(L²)Cl][PF₆]; L² = tppz ([10]PF₆), tptz ([12]PF₆). The complexes were isolated as their hexafluorophosphate salts. They have been characterized on the basis of micro analytical and spectroscopic data. The crystal structures of the representative complexes were established by X‐ray crystallography.     

Gold(I) as an Artificial Cyclase: Short Stereodivergent Syntheses of (−)‐Epiglobulol and (−)‐4β,7α‐ and (−)‐4α,7α‐Aromadendranediols

Three natural aromadendrane sesquiterpenes, (?)‐epiglobulol, (?)‐4β,7α‐aromadendranediol, and (?)‐4α,7α‐aromadendranediol, have been synthesized in only seven steps in 12, 15, and 17 % overall yields, respectively, from (E,E)‐farnesol by a stereodivergent gold(I)‐catalyzed cascade reaction which forms the tricyclic aromadendrane core in a single step. These are the shortest total syntheses of these natural compounds.     

μ3‐η2:η2:η2‐Coordination of Primary Silane on a Triruthenium Plane

A μ₃‐η²:η²:η²‐silane complex, [(Cp*Ru)₃(μ₃‐η²:η²:η²‐H₃SitBu)(μ‐H)₃] ( 2 a ; Cp*=η⁵‐C₅Me₅), was synthesized from the reaction of [{Cp*Ru(μ‐H)}₃(μ₃‐H)₂] ( 1 ) with tBuSiH₃. Complex 2 a is the first example of a silane ligand adopting a μ₃‐η²:η²:η² coordination mode. This unprecedented coordination mode was established by NMR and IR spectroscopy as well as X‐ray diffraction analysis and supported by a density functional study. Variable‐temperature NMR analysis implied that 2 a equilibrates with a tautomeric μ₃‐silyl complex ( 3 a ). Although 3 a was not isolated, the corresponding μ₃‐silyl complex, [(Cp*Ru)₃(μ₃‐η²:η²‐H₂SiPh)(H)(μ‐H)₃] ( 3 b ), was obtained from the reaction of 1 with PhSiH₃. Treatment of 2 a with PhSiH₃ resulted in a silane exchange reaction, leading to the formation of 3 b accompanied by the elimination of tBuSiH₃. This result indicates that the μ₃‐silane complex can be regarded as an “arrested” intermediate for the oxidative addition/reductive elimination of a primary silane to a trinuclear site.