- Preparation method of rocuronium bromide intermediate
-
The invention belongs to the technical field of drug synthesis, and particularly relates to a preparation method of a rocuronium bromide intermediate. To the preparation method, androsterone as shown I is used as a raw material, dehydration reaction is carried out under catalysis of an ecton reagent, and then washing is carried out. To the preparation method, the reaction temperature is reduced -2 - to -17 - 5 α - the byproduct of high-temperature reaction is reduced 40 °C, the reaction liquid is subjected to simple water washing, extraction and concentration to obtain a white solid, and the loss of the main product caused by the recrystallization of the by-product is reduced. The process is simpler, the yield is lower, and the three-waste discharge is less.
- -
-
Paragraph 0029-0041
(2021/11/26)
-
- Vecuronium bromide and its advanced intermediates: A crystallographic and spectroscopic study
-
Vecuronium bromide (Piperidinium, 1-[(2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(1-piperidinyl)androstan-16-yl]-1-methyl-, bromide; Norcuron) has been extensively used in anesthesiology practice as neuromuscular blocking agent since its launch on the market in 1982. However, a detailed crystallographic and NMR analysis of its advanced synthetic intermediates is still lacking. Hence, with the aim of filling this literature gap, vecuronium bromide was prepared starting from the commercially available 3β-hydroxy-5α-androstan-17-one (epiandrosterone), implementing some modifications to a traditional synthetic procedure. A careful NMR study allowed the complete assignment of the 1H, 13C, and 15N NMR signals of vecuronium bromide and its synthetic intermediates. The structural and stereochemical characterization of 2β,16β-bispiperidino-5α-androstane-3α,17β-diol, the first advanced synthetic intermediate carrying all the stereocenters in the final configuration, was described by means of single-crystal X-ray diffraction and Hirshfeld surface analysis, allowing a detailed conformational investigation.
- Ciceri, Samuele,Colombo, Diego,Ferraboschi, Patrizia,Grisenti, Paride,Iannone, Marco,Mori, Matteo,Meneghetti, Fiorella
-
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- Preparation method of 5alpha-androstane-2-ene-17 ketone
-
The invention discloses a preparation method of a skeletal muscle relaxant drug intermediate 5 alpha-androstane-2-ene-17 ketone, and belongs to the technical field of synthesis. According to the method disclosed by the invention, epiandrosterone is taken as a raw material and reacts with p-dodecyl benzene sulfonyl chloride under the action of a catalyst to generate sulfonate, and the 5alpha-androstane-2-ene-17 ketone is generated by elmination. The synthesis method provided by the invention can effectively reduce a double-bond position isomer 5 [alpha]-androstane-3-ene-17 ketone of the target product 5 [alpha]-androstane-2-ene-17 ketone, greatly improves the product quality, and reduces the production cost at the same time.
- -
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Paragraph 0025-0030
(2021/11/14)
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- Preparation method of rocuronium bromide intermediate 5alpha-sterane-2-ene-17-one
-
The invention discloses a preparation method of a rocuronium bromide intermediate 5alpha-sterane-2-ene-17-one. The specific steps include: sequentially adding epiandrosterone TS, a solvent and a phasetransfer catalyst into a reaction bottle, performing heating to a reaction temperature of 90-120DEG C, carrying out stirring reaction, and conducting post-treatment purification to obtain the 5alpha-sterane-2-ene-17-one. The method provided by the invention greatly shortens the reaction time, reduces byproducts, enhances the yield, reduces three wastes, lowers the production cost, is suitable forindustrial production, and has obvious social and economic benefits.
- -
-
Paragraph 0009; 0020-0031
(2020/04/02)
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- Preparation method of 5 alpha-androstane-2-ethylene-17-ketone
-
The invention discloses a preparation method of 5 alpha-androstane-2-ethylene-17-ketone. The preparation method comprises the steps of taking epiandrosterone (formula I as shown in the specification)as a raw material to give a dehydration reaction by joint catalysis of protonic acid and trifluoromethanesulfonate, and performing post-treatment, recrystallization and separation on a reaction product to form 5 alpha-androstane-2-ethylene-17-ketone (formula II as shown in the specification). The preparation method avoids the use of much organic base compound in the traditional method, has the advantages of high reaction yield, short procedure, good selectivity, low cost, less waste gas, waste water and industrial residue and the like and is a synthesis method suitable for industrial production.
- -
-
Paragraph 0021-0024; 0025-0026; 0027-0028; 0029-0044
(2019/05/08)
-
- Rapid Deoxyfluorination of Alcohols with N-Tosyl-4-chlorobenzenesulfonimidoyl Fluoride (SulfoxFluor) at Room Temperature
-
The deoxyfluorination of alcohols is a fundamentally important approach to access alkyl fluorides, and thus the development of shelf-stable, easy-to-handle, fluorine-economical, and highly selective deoxyfluorination reagents is highly desired. This work describes the development of a crystalline compound, N-tosyl-4-chlorobenzenesulfonimidoyl fluoride (SulfoxFluor), as a novel deoxyfluorination reagent that possesses all of the aforementioned merits, which is rare in the arena of deoxyfluorination. Endowed by the multi-dimensional modulating ability of the sulfonimidoyl group, SulfoxFluor is superior to 2-pyridinesulfonyl fluoride (PyFluor) in fluorination rate, and is also superior to perfluorobutanesulfonyl fluoride (PBSF) in fluorine-economy. Its reaction with alcohols not only tolerates a wide range of functionalities including the more sterically hindered alcoholic hydroxyl groups, but also exhibits high fluorination/elimination selectivity. Because SulfoxFluor can be easily prepared from inexpensive materials and can be safely handled without special techniques, it promises to serve as a practical deoxyfluorination reagent for the synthesis of various alkyl fluorides.
- Guo, Junkai,Kuang, Cuiwen,Rong, Jian,Li, Lingchun,Ni, Chuanfa,Hu, Jinbo
-
supporting information
p. 7259 - 7264
(2019/05/10)
-
- Steroid compound 3-site hydroxyl configuration inversion method
-
The invention discloses a steroid compound 3-site hydroxyl configuration inversion method. The method specifically comprises the following steps that (1) a steroid compound containing a 3-site hydroxyl reacts with an acyl chloride compound; (2) the product obtained in the step (1) and a substituting agent are subjected to SN2 nucleophilic substitution reaction under existing of a phase transfer catalyst; and (3) the product obtained in the step (2) is subjected to a hydrolysis reaction. Compared with a Mitsunobu method, the method does not need to use triphenylphosphine and azodiformate pricedhigher, and accordingly the production cost is greatly lowered; meanwhile, a p-nitrobenzoic acid derivative which seriously affects the water environment does not need to be used, and therefore the method is more environmentally friendly. The method adopts cesium acetate/18-crown ether-6 system to conduct 3-site hydroxyl configuration inversion, can remarkably reduce occurrence of side reactions,accordingly a higher reaction yield is obtained, and the method is finally applicable to industrialized production.
- -
-
-
- PyFluor: A low-cost, stable, and selective deoxyfluorination reagent
-
We report an inexpensive, thermally stable deoxyfluorination reagent that fluorinates a broad range of alcohols without substantial formation of elimination side products. This combination of selectivity, safety, and economic viability enables deoxyfluorination on preparatory scale. We employ the [18F]-labeled reagent in the first example of a no-carrier-added deoxy-radiofluorination.
- Nielsen, Matthew K.,Ugaz, Christian R.,Li, Wenping,Doyle, Abigail G.
-
supporting information
p. 9571 - 9574
(2015/08/18)
-
- NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF
-
Described herein are neuroactive steroids of the Formula (I): (Formula (I)) or a pharmaceutically acceptable salt thereof; wherein R1a and R1b are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.
- -
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Page/Page column 72; 73
(2015/02/02)
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- In vitro metabolism studies of desoxy-methyltestosterone (DMT) and its five analogues, and in vivo metabolism of desoxy-vinyltestosterone (DVT) in horses
-
The positive findings of norbolethone in 2002 and tetrahydrogestrinone in 2003 in human athlete samples confirmed that designer steroids were indeed being abused in human sports. In 2005, an addition to the family of designer steroids called 'Madol' [also known as desoxy-methyltestosterone (DMT)] was seized by government officials at the US-Canadian border. Two years later, a positive finding of DMT was reported in a mixed martial arts athlete's sample. It is not uncommon that doping agents used in human sports would likewise be abused in equine sports. Designer steroids would, therefore, pose a similar threat to the horseracing and equestrian communities. This paper describes the in vitro metabolism studies of DMT and five of its structural analogues with different substituents at the 17α position (R￡H, ethyl, vinyl, ethynyl and 2H3-methyl). In addition, the in vivo metabolism of desoxy-vinyltestosterone (DVT) in horses will be presented. The in vitro studies revealed that the metabolic pathways of DMT and its analogues occurred predominantly in the A-ring by way of a combination of enone formation, hydroxylation and reduction. Additional biotransformation involving hydroxylation of the 17α-alkyl group was also observed for DMT and some of its analogues. The oral administration experiment revealed that DVT was extensively metabolised and the parent drug was not detected in urine. Two in vivo metabolites, derived respectively from (1) hydroxylation of the A-ring and (2) di-hydroxylation together with A-ring double-bond reduction, could be detected in urine up to a maximum of 46 h after administration. Another in vivo metabolite, derived from hydroxylation of the A-ring with additional double-bond reduction and di-hydroxylation of the 17α-vinyl group, could be detected in urine up to a maximum of 70 h post-administration. All in vivo metabolites were excreted mainly as glucuronides and were also detected in the in vitro studies.
- Kwok, Wai Him,Kwok, Karen Y.,Leung, David K. K.,Leung, Gary N. W.,Wong, Colton H. F.,Wong, Jenny K. Y.,Wan, Terence S. M.
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p. 994 - 1005
(2015/11/10)
-
- Neurosteroid analogues. 18. Structure-activity studies of ent-steroid potentiators of γ-aminobutyric acid type a receptors and comparison of their activities with those of alphaxalone and allopregnanolone
-
A model of the alignment of neurosteroids and ent-neurosteroids at the same binding site on γ-aminobutyric acid type A (GABAA) receptors was evaluated for its ability to identify the structural features in ent-neurosteroids that enhance their activity as positive allosteric modulators of this receptor. Structural features that were identified included: (1) a ketone group at position C-16, (2) an axial 4α-OMe group, and (3) a C-18 methyl group. Two ent-steroids were identified that were more potent than the anesthetic steroid alphaxalone in their threshold for and duration of loss of the righting reflex in mice. In tadpoles, loss of righting reflex for these two ent-steroids occurs with EC50 values similar to those found for allopregnanolone. The results indicate that ent-steroids have considerable potential to be developed as anesthetic agents and as drugs to treat brain disorders that are ameliorated by positive allosteric modulators of GABA A receptor function.
- Qian, Mingxing,Krishnan, Kathiresan,Kudova, Eva,Li, Ping,Manion, Brad D.,Taylor, Amanda,Elias, George,Akk, Gustav,Evers, Alex S.,Zorumski, Charles F.,Mennerick, Steven,Covey, Douglas F.
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p. 171 - 190
(2014/02/14)
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- Chemical synthesis, NMR analysis and evaluation on a cancer xenograft model (HL-60) of the aminosteroid derivative RM-133
-
The aminosteroid derivative RM-133 has been reported to be a promising pro-apoptotic agent showing activity on various cancer cell lines. Following the development of solid-phase synthesis that generated a series of libraries of aminosteroid derivatives, we now report the development of a convenient liquid phase chemical synthesis of RM-133, the most promising candidate, in order to obtain sufficient quantities to proceed with the first preclinical assays. A simple and convergent six-step synthesis was designed and allowed the preparation of a gram-quantity scale of RM-133. This aminosteroid derivative was also fully characterized by NMR experiments which revealed an interesting mixture of conformers. Finally, the in vivo potency of RM-133 was evaluated on a xenograft model in nude mice with HL-60 tumors, which has resulted in the blocking of tumor progression by 57%.
- Maltais, René,Hospital, Audrey,Delhomme, Audrey,Roy, Jenny,Poirier, Donald
-
-
- 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 Δ3,5-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. Copyright
- Varela, Carla L.,Roleira, Fernanda M. F.,Costa, Saul C. P.,Pinto, Alexandra S. C. T.,Martins, Ana I. O. S.,Carvalho, Rui A.,Teixeira, Natercia A.,Correia-Da-Silva, Georgina,Tavares-Da-Silva, Elisiario
-
-
- Solid-phase chemical synthesis and in vitro biological evaluation of novel 2β-piperazino-(20R)-5α-pregnane-3α,20-diol N-derivatives as anti-leukemic agents
-
The steroid nucleus is an interesting scaffold for the development of new therapeutic agents. Within the goal of identifying anticancer agents, new pregnane derivatives were prepared by using a sequence of liquid and solid-phase reactions. After we dehydrated epi-allopregnanolone in one step with diethylaminosulfur trifluoride and generated a 2,3α-epoxide, the regio- and stereo-selective aminolysis of this epoxide enabled us to obtain a 2β-piperazino-pregnane, whose secondary amine was protected as N-Fmoc-derivative. Using the difference in reactivity between OHs 3 and 20, we linked the pregnane nucleus-selectively on the polystyrene diethylbutylsilane resin via the OH in position 20. We next achieved in parallel the coupling of an amino acid (1st level of diversity) and the coupling of a carboxylic acid (2nd level of diversity) to generate two libraries of pregnane derivatives. The compounds inhibited the HL-60 leukemia cell growth and the most potent were three compounds (PD, LPC-37 and LPC-48) with a l-proline as first level of diversity and a cyclohexyl-carbonyl, a naphthalene-2-carbonyl or a 3-acetylbenzoyl as second level of diversity. LPC-48 efficiently inhibited HL-60 cell proliferation with IC50 value of 1.9 μM and exhibited a low toxicity on normal peripheral blood lymphocytes (IC50 = 31 μM). These results encouraged us to further evaluate the biological activity of these new aminosteroids by investigating their preliminary mechanism of action.
- Jegham, Hajer,Maltais, René,Dufour, Philippe,Roy, Jenny,Poirier, Donald
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p. 1403 - 1418
(2013/01/15)
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- A mild one-pot method for conversion of various steroidal secondary alcohols into the corresponding olefins
-
The addition of Tf2O to some hydroxy steroids in the presence of excess base directly leads to steroidal olefins. This methodology is useful for the one-pot synthesis of Δ2- or Δ3-steroids under mild conditions from the corresponding alcohols. Georg Thieme Verlag Stuttgart · New York.
- Kumar, Raju Ranjith,Haveli, Shrutisagar Dattatraya,Kagan, Henri B.
-
experimental part
p. 1709 - 1712
(2011/09/14)
-
- 2-(N-SUBSTITUTED PIPERAZINYL) STEROID DERIVATIVES
-
Novel chemical agents of Formula I are described herein. More specifically, 2-(N-substituted piperazinyl) pregnane and 2-(N-substituted piperazinyl) androstane derivatives exhibiting cytotoxicity on a variety of cancer cell lines are disclosed herein. (I)
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-
Page/Page column 41; 70
(2010/06/17)
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- Synthesis of fluorinated steroids using a novel fluorinating reagent tetrabutylammonium difluorodimethylphenylsilicate (TAMPS)
-
Steroidal 3-fluoroderivatives were prepared from corresponding tosylates using tetrabutyl-ammonium difluorodimethylphenylsilicate as fluorinating agent. The reaction was tested on all four possible C-3 and C-5 stereoisomers of cholestane and 17-oxoandrostane skeletons. In this reaction only one isomer was always formed with opposite configuration at C-3 to starting tosylate. The reaction is accompanied by elimination which affords a mixture of corresponding olefines.
- Herrmann, Pavel,Kvicala, Jaroslav,Pouzar, Vladimir,Chodounska, Hana
-
experimental part
p. 1825 - 1834
(2009/06/19)
-
- Esterification of carboxylic acids and etherification of phenols with amide acetals
-
The esterification and etherification of unhindered, as well as severely hindered, carboxylic acids and phenols with basic amide acetals, such as N,N-dimethylformamide dimethyl acetal, and their side reactions are discussed. Modified procedures are descri
- Vorbrüggen, Helmut
-
experimental part
p. 1603 - 1617
(2009/04/07)
-
- DRUGS AND USES
-
The invention relates to methods to treat specified clinical disorders such as hyperglycemia, type 2 diabetes, arthritis and multiple sclerosis. The invention also provides methods to identify and characterize drugs, which are characterized in part by eliciting a variable biologic or therapeutic effect on a biomolecule at one time and relative normalization of the biomolecule at another time point. Compounds include 17α-ethynylandrost-5-ene-3β,7β, 17β-triol or androst-5-ene-3β,4β, 16α, 17β-tetrol, which can be used as reference standards to facilitate assessing and characterizing such candidate drugs.
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-
Page/Page column 85-86
(2008/06/13)
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- Preparation of androstanes related to aphidicolin
-
The preparation of 3α,4α,17β-trihydroxy-, 3α,4α,16α,17α- and 2α,3α,16α, 17α-tetrahydroxy-5α-androstane derivatives (5, 11, 18) from testosterone as steroidal analogues of diterpenoid inhibitor of DNA polymerase a, aphidicolin, is described. The crystal structure of 5α-androstane- 3α,4α,17β-triyl triacetate (6) is reported.
- Uyanik, Cavit,Yildirim, Kudret,Malay, Aslihan,Hanson, James R.,Hitchcock, Peter B.
-
p. 1545 - 1552
(2008/09/17)
-
- Conversion of epiandrosterone into 17β-amino-5α-androstane
-
A new method for synthesizing 17β-amino-5α-androstane was developed based on tigogenin. The configuration at C-17 was proved by PMR.
- Merlani,Davitishvili,Nadaraia,Sikharulidze,Papadopulos
-
p. 144 - 146
(2007/10/03)
-
- Preparation of 3,17- and 3,20-difluoro-derivatives of the androst-5-ene and pregn-5-ene series
-
Unsaturated mono- and difluorosteroids have been prepared in high yield using n-perfluorobutanesulfonyl fluoride 1. The 3,17- and 3,20-difluoro-5,6- dehydrosteroids are reported for the first time. 3-Fluoroderivatives of the androst-5-ene-17-one and 5α-an
- Decreau, Richard A.,Marson, Charles M.
-
p. 4369 - 4385
(2007/10/03)
-
- Process for preparing neuromuscular blocking agents and intermediates useful therefor
-
The present invention provides new process of preparing neuromuscular blocking agents. The process include preparing neuromuscular blocking agents using the compounds of formula I: STR1 wherein R1 is =O and X is halo; and formula II: STR2 wherein R1 and X are as defined above.
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-
-
- Fluorination of secondary and primary alcohols by thermal decomposition of electrochemically generated alkoxy triphenylphosphonium tetrafluoroborates
-
Replacement of hydroxyl groups in secondary and primary alcohols (1) with a fluorine atom arising from tetrafluoroborate anion has been performed by the electrochemical formation of alkoxy triphenylphosphonium tetrafluoroborates (2) from 1, followed by their thermal decomposition. The procedure is quite simple, involving: (1) constant-current electrolysis of a mixture of 1, Ph3P, and Ph3PH·BF4 in CH2Cl2 in an undivided cell; (2) refluxing a tetrahydrofuran or dioxane solution of the residue afforded by evaporation of the solvent in vacuo after the electrolysis. Cyclic secondary alcohols such as 3β-hydroxy steroids and 2-adamantanol are transformed into the corresponding fluorides in satisfactory yields when the geometry of the leaving group in 2 is suitable for the substitution or an elimination process for 2 to give an alkene is stereochemically forbidden. The fluorination of steroidal alcohols and 4-phenyl-1-cyclohexanol proceeded with complete inversion, demonstrating that a fluorine atom from the tetrafluoroborate anion attacks from the side opposite to the phosphonium moiety in 2 via an SN2 mechanism rather than an SN1 mechanism. The fluorination of acyclic secondary and primary alcohols was performed by the present method in reasonable yields, although the reaction for the latter required more forcing conditions, such as refluxing in dioxane.
- Maeda, Hatsuo,Koide, Takashi,Matsumoto, Sayaka,Ohmori, Hidenobu
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p. 1480 - 1483
(2007/10/03)
-
- Sulfuric acid adsorbed on silica gel. A multipurpose acid catalyst
-
A series of acid catalyzed reactions like the dehydration of alcohols, conversion of ketones to 1,3-dioxolanes and their hydrolysis, α, β- unsaturated ketones to enol ethers, and alcohols to methyl-methoxyethyl ethers are performed efficiently in high yield with sulfuric acid adsorbed on silica gel as catalyst.
- Chavez,Suarez,Diaz
-
p. 2325 - 2339
(2007/10/02)
-
- Facile Preparation of Tetrabutylphosphonium Fluoride and Its HF Adducts. New Fluoride Anion Sources for Selective Nucleophilic Fluorination
-
Anhydrous tetrabutylphosphonium hydrogen bifluoride (2), dihydrogen trifluoride prepared from aq. tetrabutylphosphonium hydroxide and aq.HF, and tetrabutylphosphonium fluoride prepared from 2 and BunLi were shown to be useful fluoride sources for selective nucleophilic fluorination of oxiranes, alkyl halides, alcohols and sulfonates of aliphatic and steroidal species.
- Seto, Hideharu,Qian, Zhao-hui,Yoshioka, Hirosuke,Uchibori, Yukitaka,Umeno, Masayuki
-
p. 1185 - 1188
(2007/10/02)
-
- STEROIDS. LIV. SYNTHESIS OF 17β-AMINO-5α-ANDROSTAN-3α-OL FROM EPIANDROSTERONE
-
17β-Amino-3α-hydroxy-5α-androstane was synthesized from epiandrosterone by: a) epimerization at C3 by the Luttrell-Lochaus method to androsterone followed by reductive amination; b) Leuckart-Wallach amination followed by epimerization of the 3β-hydroxy-17β-formamido-5α-androstane at C3 by the Mitsunobu method.
- Nadaraia, N. Sh.,Sladkov, V. I.,Suvorov, N. N.
-
p. 682 - 686
(2007/10/02)
-
- p-Toluenesulfonic Acid Adsorbed on Silica Gel: An Efficient Dehydrating Agent of Alcohols
-
Secondary and tertiary alcohols are efficiently dehydrated by reaction with p-toluenesulfonic acid supported on silica gel.In particular, the procedure allows the direct conversion of 3-hydroxy-steroids into Δ2-olefins or Δ3,5-dienes, without passing through the mesylate or tosylate esters.
- D'Onofrio, Franco,Scettri, Arrigo
-
p. 1159 - 1161
(2007/10/02)
-
- 1H NMR Analyses, Shielding Mechanisms, Coupling Constants, and Comformations is Steroids Bearing Halogen, Hydroxy, Oxo Groups, and Double Bonds
-
The 1H NMR analyses of 16 5αH-androstanes and one progesterone analogue furnish shifts and coupling constants for the basic steroid skeleton and substituent-induced shifts (SIS) for oxo, hydroxy, and halogen groups as well as for a Δ double bond.It is shown how a single 2D experiment complemented by a NOE difference spectrum can lead to complete assignments even with the most complicated spin systems compirising, e.g., 29 strongly coupled protons within only 1 ppm; the accurancy of information from 2D techniques is evaluated by comparison to some 1D and computer-simulated spectra.On the basis of up to six simultaneously observable couplings, a special approach is used to scan the conformational space of particularly flexible parts.Intermediate conformations between half-chair and twist are obtained with a torsional C14-C15-C16-C17 angle of φ ca. 20 deg for the D ring with a sp2 (17-oxo) carbon and of φ ca. 10 deg with only sp3 carbon atoms; the observed flat profiles, however, allow also for mixtures of different conformations, which is supported by MM2 calculations.For the Δ-3-oxo A ring, a sofa conformation is favored compared to a half-chair geometry.The observed shielding effects of heterosubstituents are partially at variance with the few earlier observations, which were mostly based on polysubstituted compounds.Classical shielding mechanisms were evaluated with the program SHIFT, based on force-field-minimized structures.Steric-induced shielding dominates in the hydrocarbon, leading to upfield shifts increasing with the number of 1,3-diaxial interactions.Linear electric-field effects predict, e.g., the shielding difference between equatorial and axial protons vicinal to C-Hal bonds and the deshielding observed for diaxial C-Hal/C-H bond arrangements.A combination of anisotropy and electric-field effects explains all shifts observed in the ketones with the exception of protons vicinal to C=O; a multilinear regression analysis leads to Δχ1C=O = -36 (-27) and Δχ2C=O = -24 (-21) (10-3 cm3/molecule, old ApSimon values in parentheses); it is, however, demonstrated, that an analysis on the basis of NMR shifts alone leads to broad ranges of parameters.Parallels between 1H and 13C NMR shifts are drawn, particularly at γ and θ positions to C-Hal bonds.
- Schneider, Hans-Joerg,Buchheit, Ulrich,Becker, Norman,Schmidt, Guenter,Siehl, Ulrich
-
p. 7027 - 7039
(2007/10/02)
-
- The Solvolysis of 4β-Hydroxy-3β-p-tolylsulphonyloxyandrost-5-enes
-
The solvolysis of 3β-p-tolylsulphonyloxyandrost-5-enes in acetic acid containing sodium acetate, is retarded by the presence of a 4β-acetoxy- or hydroxy-group.The products of solvolysis include the A-nor-3-formyl-steroids except in the presence of a 7-ketone.
- Hanson, James R.,Wadsworth, Harry J.
-
p. 933 - 937
(2007/10/02)
-
