Zur lokalisierung funktioneller gruppen mit hilfe der massenspektrometrie—VIII : 6-hydroxy-androstan-3,17-dione und 6,17β-dihydroxy-androstan-3-one

5β-androstan-3-ones carrying a 6α-OH group show in their mass spectra a key-ion indicating the loss of water and C-1 to C-4 as C₄H₅O? particle. 6β-OH isomers lose instead C-1 to C-4 in form of C₄H₇O?.In 6α-hydroxy-androstan-3-ones differentiation between the connection of the A/B-ring system is possible, because in 5α-isomers the loss of C-3 to C-7 occurs as a C₅H₆O₂ particle, while the 5β-isomers lose the same C atoms as a C₅H₇O? unit.Compounds with a 6β-OH group in an A/B trans connected ring system show a tendency for thermal water elimination. After rearrangement of the double bond in 4,5 position the typical fragments for 3-keto-Δ⁴-steroids are obtained.Occasionally a strong influence of a 6-OH group on fragmentation reactions in the D-ring system is observed: The presence of a 6α-OH group in an androstan-3,17-dione enhances the loss of C-16 and C-17 in the form of acetaldehydenol. Also the connection of the A/B-ring system may have a considerable influence on this type of reaction: In 6,17β-dihydroxy-androstan-3-ones only by trans connection of the A/B-ring system, C-16 and C-17 are lost with high probability after water elimination.     

Agnatasterone A and B,Unusual Pregnane Steroids Isolated from the North-East Atlantic Sponge Axinella agnata

Two novel pregnatrienolones isolated in very small amounts from the North-East-Atlantic demosponge Axinella agnata (Tetractinomorpha, Axinellida) are unique in having C(2)?C(3) (or C(3)?C(4)), C(7)?C(8), and C(16)?C(17) bonds and a 12β-OH group which, being strongly H-bonded to a 20-keto group, resists acylation. ¹H- and ¹³C-NMR spectroscopy of the steroids and of products of their selective epoxidation or reduction allow us to propose the structures (+)-12β-hydroxy-5α-pregna-2,7,16-trien-20-one ( = agnatasterone A, (+)- 1 ), and (+)-12β-hydroxy-5α-pregna-3,7,16-trien-20-one ( = agnatasterone B. (+)- 5 ), for the two steroids with minimal recourse to model compounds.     

Synthesis of δ-cyclohexyl- and δ,δ-alkylene-α,α-dicarbonyl-substituted dienes and study of their valence isomerization

β-Cyclohexylacrolein, β-cyclohexylmethacrolein, or α-cycloalkylidenalkanals were condensed with methyl acetoacetate or dimethyl malonate to give the δ-cyclohexyl- and δ,δ-alkylene-substituted α,α-dicarbonyl-containing α,β∶γ,δ-dienes. The structures of the reaction products were studied using¹H NMR,¹³C NMR, and UV spectroscopy. The diene keto esters bearing no substituents at the γ-position were shown to be in fact three-component equilibrium mixtures comprised ofE- andZ-isomers of the diene (at the α,β bond) and a corresponding 2H-pyran. On the other hand, for keto esters with a Me group at the γ-position the equilibrium is shifted entirely to the 2H-pyrans. In contrast with the keto esters, dienic diesters exist only in the open form.     

MOF-808/BiOCl复合材料的制备及其光催化性能

将高稳定性的MOF-808与BiOCl结合,采用简便的水热法制备出新型MOF-808/BiOCl复合异质结材料。以环丙沙星(CIP)为污染物,探究复合材料MOF-808/BiOCl对CIP的光催化性能。发现含有10% MOF-808的复合材料(MOF-808/BiOCl-10%)表现出最佳的光催化活性。在紫外光照射20 min内,MOF-808/BiOCl-10%对CIP的光催化降解效率高达94.7%。通过X射线粉末衍射、扫描电镜、红外光谱、荧光光谱、紫外可见漫反射光谱、光电流、电化学阻抗等表征技术来考察材料的物相组成、形貌以及光电化学性质。紫外可见漫反射光谱的结果表明,MOF-808/BiOCl-10%材料光吸收范围得到提高。同时进行了自由基捕获实验。基于以上实验数据,提出了MOF-808/BiOCl复合材料可能的光催化机理。     

Fourier transform 13C nuclear magnetic resonance studies of steroids—II : Derivatives of 17β-(2,5-dihydro-5-oxo-3-furyl)-3β,5α,6-trihydroxyandrostane

The natural abundance ¹³C NMR spectra of derivatives of 17β-(2,5-dihydro-5-oxo-3-furyl)-3β,5α,6-trihydroxy androstane have been measured and completely assigned. The substituent chemical shifts (S.C.S's) for 11α- and 17α-OH substitution are evaluated. The magnitude and sign of the S.C.S.'s are discussed and compared with previous results from the literature.     

Metal-organic frameworks MOF-808-X as highly efficient catalysts for direct synthesis of dimethyl carbonate from CO2 and methanol

A series of metal-organic frameworks MOF-808-X (6-connected) were synthesized by regulating the ZrOCl₂·8H₂O/1,3,5-benzenetricarboxylic acid (BTC) molar ratio (X) and tested for the direct synthesis of dimethyl carbonate (DMC) from CO₂ and CH₃OH with 1,1,1-trimethoxymethane (TMM) as a dehydrating agent. The effect of the ZrOCl₂·8H₂O/BTC molar ratio on the physicochemical properties and catalytic performance of MOF-808-X was investigated. Results showed that a proper ZrOCl₂·8H₂O/BTC molar ratio during MOF-808-X synthesis was fairly important to reduce the redundant BTC or zirconium clusters trapped in the micropores of MOF-808-X. MOF-808-4, with almost no redundant BTC or zirconium clusters trapped in the micropores, exhibited the largest surface area, micropore size, and the number of acidic-basic sites, and consequently showed the best activity among all MOF-808-X, with the highest DMC yield of 21.5% under the optimal reaction conditions. Moreover, benefiting from the larger micropore size, MOF-808-4 outperformed our previously reported UiO-66-24 (12-connected), which had even more acidic-basic sites and larger surface area than MOF-808-4, mainly because the larger micropore size of MOF-808-4 provided higher accessibility for the reactant to the active sites located in the micropores. Furthermore, a possible reaction mechanism over MOF-808-4 was proposed based on the in situ FT-IR results. The effects of different reaction parameters on DMC formation and the reusability of MOF-808-X were also studied.     

Bismuth(III) triflate-catalyzed rearrangement of 16α,17α-epoxy-20-oxosteroids. Synthesis and structural elucidation of new 16α-substituted 17α-alkyl-17β-methyl-Δ-18-norsteroids

The use of bismuth(III) triflate for the rearrangement of 16α,17α-epoxy-20-oxosteroids is reported. The reactions occur under truly catalytic conditions to afford novel 17α-alkyl-17β-methyl-Δ¹³-18-nor products bearing different O-containing substituents at C16. When the reaction is performed in the absence of acylation agent a mixture of isomeric 16α- and 16β-hydroxy derivatives is obtained, whereas when carried out in the presence of such reagents, the reaction selectively affords the corresponding 16α-acyl rearranged products. The chemoselective rearrangement of 5β,6β;16α,17α-diepoxy-20-oxopregnan-3β-yl acetate to afford a ‘backbone’ rearranged product bearing the 16α,17α-epoxide group is also reported. Some mechanistic considerations are provided. All rearranged products were the subject of comprehensive structural elucidation, by the use of X-ray crystallography and 2D NMR.     

Potential Bile Acid Metabolites. 5.1 12B-Hydroxy Acids by Stereoselective Reduction

According to previous research the practical route² to 12β-hydroxycholanic³ acids was by Raney nickel catalytic hydrogenation of the corresponding keto acids, but the method suffers from several disadvantages: (1) the required ratio of catalyst to substrate is inordinately high, (2) the reaction is usually slow, with complete reduction time ranging from 6 hours (12-oxocholanic acid) to 48 hours (certain dihydroxy keto acids), (3) recovery from the adsorbed product from the catalyst is incomplete, and (4) with long reaction times side reactions can occur, as was recently reported^2c that during Raney nickel reduction of methyl 3β, 7α-dihydroxy-12-oxocholanate (1), requiring 48 hours for completion, partial inversion at C-3 took place.     

Autooxidation of Δ17(20)-20-hydroxy derivatives of steroids. Synthesis of 3β-acetoxy-17α-hydroperoxy-16α-methylpregn-5-en-20-one and its reduction to 17α-hydroxy derivative

An efficient procedure was proposed for the synthesis of 3β-acetoxy-17α-hydroperoxy-16α-methylpregn-5-en-20-one. Optimal conditions were found for the combined process including 1,4-addition of methylmagnesium bromide at the Δ¹⁶-20-oxo fragment of dehydropregnenolone acetate and autooxidation of resulting bromomagnesium 3β-acetoxy-16α-methylpregna-5,17(20)-dien-20-olate. The subsequent reduction of the 17α-hydroperoxy group and hydrolysis of the 3β-acetoxy group afforded 17α-hydroxy-16α-methyl-substituted dehydropregnenolone acetate and its 3-hydroxy analog in high yield.     

Zur lokalisierung funktioneller gruppen mit hilfe der massenspektrometrie—XI : 3,12,17β-trihydroxy-androstane, 12,17β-dihydroxy-androstan-3-one,3,12-dihydroxy-androstan-17-one und 12-hydroxy-androstan-3,17-dione

Mass spectrometric degradation reactions of steroids with hydroxy groups in positions 12 and 17β depend on the configuration of the C-12 hydroxy group. In compounds with a 12α-hydroxy group, this group and the hydrogen in position 17α is eliminated as H₂O. This reaction is followed by loss of a methyl radical. In the isomers with a 12β-hydroxy group this reaction is not possible. Here the loss of carbon 15–17 dominates the production of an ion by loss of two molecules of water. Key ions of mass 97 as well as M-44 and M-74 ions are produced by 17 keto steroids with a hydroxy group in position 12. If the rings A and B are cis-connected less specific degradation reactions are observed.     

A stereochemical examination of the equine metabolism of 17alpha-methyltestosterone

An investigation was conducted into the stereochemistry of the equine urinary metabolites of 17α-methyltestosterone observed after oral administration. Standards of the complete range of C3/C5/C16 stereoisomeric 17α-methylandrostane-3,17β-diols, 17α-methylandrostane-3,16,17β-triols and 17α-hydroxymethylandrostane-3,17β-diols were purchased or synthesised, and were used to unequivocally identify the absolute structures of the metabolites. Phase I metabolism was found to involve combinations of Δ⁴-3-ketone reduction with both 5α,3β- and 5β,3α-stereochemistry, hydroxylation at C16 with both 16α- and 16β-stereochemistry and hydroxylation of the 17α-methyl substituent. Phase II metabolism involved mainly sulfation with a lesser degree of β-glucuronidation.     

Insights into the Synthesis of Steroidal A‐Ring Olefins

The classical synthesis, followed by purification of the steroidal A‐ring Δ¹‐olefin, 5α‐androst‐1‐en‐17‐one ( 5 ), from the Δ¹‐3‐keto enone, (5α,17β)‐3‐oxo‐5‐androst‐1‐en‐17‐yl acetate ( 1 ), through a strategy involving the reaction of Δ¹‐3‐hydroxy allylic alcohol, 3β‐hydroxy‐5α‐androst‐1‐en‐17β‐yl acetate ( 2 ), with SOCl₂, was revisited in order to prepare and biologically evaluate 5 as aromatase inhibitor for breast cancer treatment. Surprisingly, the followed strategy also afforded the isomeric Δ²‐olefin 6 as a by‐product, which could only be detected on the basis of NMR analysis. Optimization of the purification and detection procedures allowed us to reach 96% purity required for biological assays of compound 5 . The same synthetic strategy was applied, using the Δ⁴‐3‐keto enone, 3‐oxoandrost‐4‐en‐17β‐yl acetate ( 8 ), as starting material, to prepare the potent aromatase inhibitor Δ⁴‐olefin, androst‐4‐en‐17‐one ( 15 ). Unexpectedly, a different aromatase inhibitor, the Δ^3,5‐diene, androst‐3,5‐dien‐17‐one ( 12 ), was formed. To overcome this drawback, another strategy was developed for the preparation of 15 from 8 . The data now presented show the unequal reactivity of the two steroidal A‐ring Δ¹‐ and Δ⁴‐3‐hydroxy allylic alcohol intermediates, 3β‐hydroxy‐5α‐androst‐1‐en‐17β‐yl acetate ( 2 ) and 3β‐hydroxyandrost‐4‐en‐17β‐yl acetate ( 9 ), towards SOCl₂, and provides a new strategy for the preparation of the aromatase inhibitor 12 . Additionally, a new pathway to prepare compound 15 was achieved, which avoids the formation of undesirable by‐products.     

MOF-808 as a Highly Active Catalyst for the Diastereoselective Reduction of Substituted Cyclohexanones

Zr-containing MOF-808 is an excellent heterogeneous catalyst for the diastereoselective Meerwein–Ponndorf–Verley reduction of substituted cyclohexanones. The presence of substituents at the 2 or 3 position of the cyclohexanone ring strongly drives the reaction towards the formation of one of the two possible isomers. For 3-methyl cyclohexanone, the available space inside the MOF pores allows the formation of the bulkier transition state leading to the thermodynamically stable 3-cis-cyclohexanol. For 2-methyl cyclohexanone, the reaction rate is much slower and the final diastereoselectivity depends on the size of the alcohol used. Finally, reduction of 2-phenyl cyclohexanone is considerable faster over MOF-808 than for any other catalyst reported so far. The large size of the phenyl favors the selective formation (up to 94% selectivity) of the cis-alcohol, which goes through a less hindered transition state.     

MO-TMS Derivatives of Human Urinary Steroids for GC and GC-MS Studies

Abstract

Sterically hindered 17α-hydroxyl groups in steroids are silylated by trimethylsilylimidazole (TSIM) at 100° C. Decreasing rates of reaction were found for the following structures: 17α, 20β, 21-triol > 17α, 20α-diol > 17α, 20α, 21-triol. When methoxime derivatives are formed as the first step, HCL present in the excess of reagent catalyses the silylation reaction of hydroxyl groups. A simple procedure is described whereby methoxime (MO) derivatives are formed in 15 minutes at 60° C (the 11-one group does not react under these conditions) and persilylated compounds are then prepared in 2 hours at 100° C by reaction with trimethylsilylimidazole.     

Selectivite de la reduction de l'androsten-4 dione-3,17 et de la progesterone par divers borohydrures: role de l'assistance electrophile par le cation ou un solvant hydroxyle

The reduction of Δ⁴-androsten-3, 17 dione 1 and of progesterone 2 by nBu₄NBH₄ is highly chemioselective: in THF only the a-enone moiety is reduced, the saturated C₁₇ or C₂₀ keto group being kept unchanged. When TMEDA is added, saturated alcohols are obtained, without any allylic alcohol when the reaction goes to completion. However this reduction is poorly stereoselective as 70:30 mixtures of A/B cis and trans ring junction compounds are obtained. In MeOH, the saturated keto group is more than 90% selectively reduced. However, the reduction of 1 and 2 by LiBH₄ and Zn(BH₄)₂ is poorly chemioselective. These results are interpreted in terms of competition between electrophilic assistance and steric effects.     

Steroids and sex hormones. Quassinoid bitter principles. I. 1-oxo-2-methoxy-4 alpha-methyl-17 beta-hydroxy-delta2-5 alpha-androstene as a model for the ring a structure of quassine]

Starting from 3-oxo-17β-hydroxy-Δ¹-5α-androstene (2b) the preparation of 1-oxo-2-methoxy-4α-methyl-17β-hydroxy-Δ²-5α-androstene (9), a compound with the ring A structure of quassine (1) is described. The key problem of the reaction sequence is shown to be the monomethylation at C(4).     

Hydroxy group substituent effects on 1H NMR chemical shifts in the structural elucidation of spirostanes

¹H NMR chemical shifts in spirostanes have been determined by spin-decoupling difference spectroscopy. Substituent effects of 7β-OH on 15-methylene proton shifts, 1β-OH on 11α- and 2α-proton shifts and 6α-OH on 4α-proton shifts have been determined and used in the structural assignment of spirostanes.     

An improved synthesis of pennogenin

An improved synthesis of pennogenin, a bioactive component of Chinese herb “Chonglou” (Paris), is described. A ring-switching process opened the ring E of diosgenin and allowed the use of a hydroxyl-directed diboration/oxidation to introduce C17α-OH, hence eliminating the use of OsO₄. This strategy might be rendered to synthesize similar steroids with C17α-OH.     

Divergent syntheses of all 16 carbasugar stereoisomers via stereoconversion of carba-β-d-altropyranose derivatives

We have developed practical synthetic routes to enantiopure d- and l-carba-β-altrose derivatives and all the possible stereoisomers via their divergent stereoconversions. Carba-β-d-altrose was prepared from 3-cyclohexene-1-carboxylic acid and converted to carba-β-d-mannose, carba-β-d-idose, and carba-β-d-talose derivatives via regio- and stereoselective oxidation/reduction of 3-OH and/or 4-OH. The four carbasugar stereoisomers were then transformed to the remaining 12 carbasugar stereoisomers and their 1,2-epoxides by regio- and stereoselective manipulation of hydroxyl groups in C1 and C2, which includes oxidation/reduction, Mitsunobu’s reaction, olefination/dihydroxylation, and epoxidation/ring-opening protocols.     

New brassinosteroid analogs having nitrogenated functionalities at C3 to provide more information about the brassinosteroid-receptor interaction

An efficient synthesis of different brassinosteroid derivatives with an azide or an amine function at C3 without any function at C2 and their biological activity evaluation in the rice lamina inclination test is described. The key step in the synthetic strategy involves a nucleophilic substitution by azide of an activated 3β-OH followed by reduction to amine. The activity elicited by 7 and 9 having an azide group, in contrast with the residual ones elicited by their corresponding amines, suggests that the 3α-OH group of an active brassinosteroid could act as acceptor in the putative hydrogen bonding interaction with the receptor/s.