10.1021/jm8009316
The research details the rational design and synthesis of a novel nonsteroidal androgen receptor antagonist, PF-998425, intended for dermatological applications such as sebum control and treatment of androgenetic alopecia. The compound was designed to be potent, selective, and devoid of phototoxicity, a common issue with similar drugs. The study involved high-throughput screening using a [3H]DHT competitive ligand binding assay and MDA-MB-453-MMTV-luci cell line to identify active compounds. The synthesis of PF-998425 included a series of chemical reactions starting from 4-fluoro-2-(trifluoromethyl)benzonitrile and cyclohexanone, leading to the desired cis-alcohol (-)-6a with a key step being an asymmetric epoxidation using Jacobsen’s (S,S)Mn(III)-salen complex catalyst. The compound's activity was confirmed through in vitro assays, including binding assays and cellular functional assays, with IC50 values indicating potency. The compound's selectivity was tested against other nuclear hormone receptors, and its pharmacokinetics, in vivo activity, and safety were evaluated using various models and assays, including the 3T3 neutral red uptake (NRU) phototoxicity test, metabolic stability in rat liver microsomes, and pharmacokinetics in dogs. The results showed that PF-998425 was active in reducing sebum and stimulating hair growth without causing phototoxicity or significant systemic side effects, making it a promising candidate for topical dermatological treatments.
10.1021/jo00249a037
The research focused on the regioselective reactions of the 5-(ethylthio)furan-2(5H)-one anion with various electrophilic reagents. The purpose of the study was to explore the reactivity of this anion towards different electrophilic species, such as Michael acceptors, carbonyl compounds, alkyl halides, and acyl halides, with the aim of selectively forming new bonds, particularly carbon-carbon bonds, at the 3- and 5-positions of 2(5H)-furanones. The researchers used a variety of chemicals in their experiments, including 5-(ethylthio)furan-2(5H)-one, lithium diisopropylamide (LDA), potassium carbonate, propionaldehyde, acetyl chloride, ethyl chloroformate, cyclohexenone, methyl acrylate, and cyclohexanone. The conclusions drawn from the study indicated that the reactions proceeded with high regioselectivity, controlled by the nature of the electrophile, and provided a simple and mild method for the synthesis of important substituted lactones, which has wide potential utility in organic synthesis.
10.1021/jo00395a028
The study investigates the synthesis and structural elucidation of various halogenated alicyclic monoterpenes derived from the red algae Plocamium violaceum and Plocamium cartilagineum. Key chemicals involved include cyclohexanone, which is used as a reactant in the initial synthesis steps, and aluminum isopropanoxide, which acts as a catalyst. Lithium acetylide-ethylenediamine complex is employed to introduce ethynyl groups, while hydrochloric acid and sodium bicarbonate are used in subsequent steps for acidification and neutralization, respectively. The study also involves the isolation and characterization of specific compounds such as plocamene D, plocamene D', plocamene E, and plocamene C, which are identified through spectroscopic methods including NMR and GC/MS. These compounds exhibit distinct structural features and mass spectral fragmentation patterns, providing insights into their biosynthetic pathways and potential biological activities.
10.1016/j.jorganchem.2009.02.018
The research focuses on the catalytic hydrogenation of C@O and C@N bonds using rhodium and iridium thiolate complexes that facilitate the heterolysis of H2. The study investigates the catalytic activity of coordinatively unsaturated rhodium and iridium complexes, Cp*M(PMe3)(SDmp) (1a: M = Rh; 1b: M = Ir), in the hydrogenation of benzaldehyde, N-benzylideneaniline, and cyclohexanone under mild conditions at low temperatures and 1 atm of H2. The key reactants include the metal complexes 1a and 1b, benzaldehyde, N-benzylideneaniline, and cyclohexanone. The experiments involved the generation of M–H/S–H complexes Cp*M(PMe3)(H)(HSDmp) (2a: M = Rh; 2b: M = Ir) through H2 heterolysis by 1a or 1b, which were proposed to transfer both M–H hydride and S–H proton to the substrates. The catalytic reactions were终止 by the dissociation of H-SDmp from the metal centers of 2a and 2b. The analyses used to monitor the reactions and characterize the products included 1H, 13C{1H}, and 31P{1H} NMR spectroscopy, infrared spectroscopy, ESI-MS spectrometry, and elemental analysis. The structure of one of the complexes formed during the reaction was confirmed by X-ray diffraction analysis.
10.1016/j.tetlet.2009.03.006
The study presents the stereoselective total synthesis of synparvolide B and epi-synparvolide A, complex molecules containing an a,b-unsaturated d-lactone motif, which are of interest to medicinal chemists due to their presence in plants with potent biological activities. The synthesis was achieved through a convergent approach, with key steps including Noyori asymmetric Transfer Hydrogenation of ketone and Wadsworth–Emmons olefination reaction. Various chemicals were used in the process, such as L(+)-DET, cyclohexanone, pTSA, LiAlH4, TsCl, NaBH4, I2, TPP, imidazole, alkyne 13, n-BuLi, ethylchloroformate, N-methyl methoxy aminohydrochloride salt, and others, serving as starting materials, reagents, and catalysts in the multi-step synthesis process. These chemicals were essential for constructing the complex molecular structures of the target compounds, enabling their synthesis for further biological evaluation and potential therapeutic property identification.
10.1016/j.tetasy.2011.05.008
The study focuses on the development of a simple, inexpensive, and efficient method for asymmetric direct aldol reactions using L-prolinamide as a recyclable organocatalyst. The main objective was to obtain highly enantiomerically enriched anti-aldol products, which are valuable in industrial applications. A series of prolinamides (compounds 1-10) were synthesized and tested for their catalytic activity in the asymmetric aldol reaction between benzaldehyde and cyclohexanone. The study found that prolinamide 6, in particular, showed high catalytic efficiency with only 5 mol % catalyst loading and 4 equivalents of ketone, yielding aldol products with high diastereoselectivity (up to anti/syn 99:1) and enantioselectivity (up to 99%), and significantly enhanced reaction yield (up to 99%). The catalyst could be easily recovered and reused without a significant decrease in enantioselectivity, making it a promising candidate for large-scale industrial applications. The chemicals used in the study included various prolinamides, benzaldehyde, cyclohexanone, and acetic acid, serving as catalysts, reactants, and a cocatalyst, respectively, to facilitate the aldol reaction and improve its efficiency and selectivity.
10.1055/s-1982-30055
The research details an improved procedure for the Michael reaction of chalcones, a valuable C-C bond forming reaction commonly catalyzed by alkali metal hydroxides or alkoxides. The study aimed to achieve better results using weaker bases such as piperidine, tertiary amines, or quaternary ammonium hydroxides. The researchers found that partially dehydrated commercial barium hydroxide efficiently catalyzed Michael reactions of chalcones with active methylene compounds like ethyl malonate, ethyl acetoacetate, acetylacetone, nitromethane, and enolizable ketones such as cyclohexanone and acetophenone. The process involved stirring the components in ethanol at reflux or room temperature, yielding products with sharp melting points and single spots on T.L.C., and spectra that matched those of recrystallized products. The yields were generally higher than reported yields or at least of the same order, and the method was operationally simpler compared to other basic catalysts. The study concluded that while the barium hydroxide catalyst was cheap and easily prepared, its catalytic activity decreased over time when exposed to moist air, and the use of solvents other than ethanol or methanol led to poorer yields.
10.1016/S0040-4039(00)87795-3
The study investigates the stereoselectivity of ketal Claisen rearrangements involving ketals of simple cyclic ketones such as cyclopentanone, cyclohexanone, and cycloheptanone. The reactions of these ketals with allylic alcohols produce mixtures of diastereomeric products, with the m isomer generally favored. The selectivity is influenced by enolization processes, particularly in the 5- and 6-membered ring systems. The study finds that the initial selectivity is quite good, especially when the allylic alcohol contains a methyl substituent, which induces significant diastereoselectivity. The identity of the major Claisen product is confirmed through independent methods like Wittig olefination and Cope rearrangement. The overall yields are good, and useful reaction products can be obtained, although the separation of isomers varies in difficulty depending on the cyclic ketone used. The researchers are working to expand the scope of the reaction to achieve higher diastereoselectivity.
10.1016/S0040-4020(98)01173-9
The study explores the use of the HOF·CH3CN complex for the a-hydroxylation of various carbonyl compounds. The HOF·CH3CN complex is prepared by bubbling nitrogen-diluted fluorine through aqueous acetonitrile and serves as an efficient oxygen transfer agent. It is used to oxidize the a-carbon of carbonyl compounds, converting them into their respective a-hydroxy derivatives. The study involves the use of trimethylsilyl enol ethers derived from ketones, esters, and acids as substrates. These enol ethers react with the HOF·CH3CN complex under mild conditions, typically at room temperature or below, yielding high-quality a-hydroxy products. The study demonstrates the versatility and efficiency of this method for a wide range of carbonyl compounds, including cyclic ketones, aliphatic ketones, esters, and carboxylic acids, with yields often exceeding 80%. The findings highlight the potential of the HOF·CH3CN complex as a valuable tool in organic synthesis for the functionalization of carbonyl compounds.
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