New synthesis of pentacyclic steroids by stereoselective epoxide ring opening

A stereoselective synthesis of pentacyclic steroids has been achieved. Starting from commercially available cholic acid 1, followed by asymmetric epoxidation and by stereoselective epoxide ring opening, employing nucleophilic species, the corresponding products were afforded in good yields. The compounds were being evaluated for their biological activity.     

Intramolecular guanidine epoxide ring opening reactions

The synthesis of a range of cyclic guanidines via intramolecular ring opening of epoxides or iodocyclisation is reported. A preliminary investigation of the glycosidase inhibitory activity of these substances is also discussed.     

Regioselective ring opening of alkylidenecyclopropanone silyl acetals

Alkylidenecyclopropanone silyl acetals are readily available from the reaction of an alkylidenemethyliodonium salt and ketene silyl acetals in the presence of triethylamine. The three different C-C bonds of the cyclopropane ring can be selectively cleaved with HCl, Lewis acid, or fluoride. The alkylideneallyl cation formed via the cleavage of C2-C3 bond with Lewis acids shows further selectivity in reacting with a nucleophile.     

Regioselective epoxide opening of epoxyamides derived from d-glucose. Cyclization approaches to azepanes

Epoxyamides obtained from d-glucose have been evaluated as tools to obtain polyhydroxyazepanes. The stereoselectivity in formation of the epoxyamides was proven to be dependent of the protecting group. The conversion of epoxyamides into epoxyalcohols was necessary to obtain polyhydroxyazepanes, because the direct cyclization of 2-N-amides to azepanecarboxamides was unsuccessful from derivatives obtained from d-glucose. Epoxyamides and epoxyalcohols were regioselectively (alpha) opened by nitrogen nucleophiles. Reduction of diethyl epoxyamide by catalytic transfer hydrogenation gave the alpha deoxy product.     

Regioselective synthesis of 2-amino-isophthalonitriles through a ring transformation strategy

An expeditious synthesis of several 2-amino-isophthalonitriles and their biaryl compounds is described and illustrated by carbanion-induced ring transformation of functionalized 2H-pyran-2-ones with malononitrile in excellent yields. The strength of the reaction lies in the creation of an aromatic ring at room temperature from six-membered lactones under mild reaction conditions. This approach is an alternative to Diels-Alder reactions of 2H-pyran-2-ones with dienophiles, which require forcing thermal conditions to obtain benzene derivatives.     

Regioselective ring opening of aziridines with activated DMF complexes: a facile synthesis of β-haloamines

A wide variety of aziridines were converted to the corresponding β-haloamines using activated DMF complexes in good to excellent yields with high regioselectivity.     

Regioselective ring opening of 2-methylaziridine derivatives with F- and F-fluoride

Regioselectivity of the nucleophilic ring opening of N-benzoyl (Bz) and N-benzyloxycarbonyl (Cbz) activated 2-methylaziridines with anhydrous tetramethylammonium fluoride, anhydrous hydrogen fluoride, and ¹⁹F or [¹⁸F]-labelled potassium cryptand fluoride ([K₂₂₂][^18/19F]) were investigated. Whereas all reactions with rigorously anhydrous N(CH₃)₄F did not ring-open the aziridines, reactions with anhydrous HF exclusively yielded the 2-fluoropropanamine derivatives. Reactions of Bz-protected and Cbz-protected 2-methylaziridine with [K₂₂₂][^18/19F] yielded the 2-fluoropropanamine and 1-fluoro-2-propanamine derivatives as the major products, respectively, and represents the first example of regiocontrol during ring opening of aziridines with [¹⁸F]-fluoride.     

Regioselective ring opening of the chiral non-racemic furoindolizidinols. New entry to alkylindolizidinediol derivatives

New homochiral 6-ethyl-7,8-indolizidinediol derivatives, related to the bioactive dihydroxylated indolizidine alkaloids, are reported to be easily accessible in four or five steps from enantiopure 9-hydroxy-octahydrofuro[3,2-f]indolizin-6(2H)-ones in good overall yields and high diastereomeric purities. The simple procedure used herein involves a regiospecific THF-ring opening as a key step, in addition to the C–Br linkage reduction, and the alcohol deprotection followed by lactam reduction.     

Enantioselectivity of epoxide hydrolase catalysed oxirane ring opening: a 3D QSAR study

A 3D QSAR analysis (quantitative structure activity relationships) of a set of 2,2-disubstituted epoxides, substrates for epoxide hydrolases originating from four different organisms, was conducted by CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis), with respect to the enantioselective ring opening to the corresponding vicinal diol. Structural variations of the substrates include alkyl chains of different lengths, unsaturated moieties ((E)- and (Z)-alkenyl, alkinyl, aryl) and electronegative groups (ether oxygens, halogen atoms) at different locations within the 2-substituent group. Generally, all four organisms, namely Rhodococcus ruber NCIMB 11216, Rhodococcus ruber DSM 43338, Rhodococcus ruber DSM 44540 and Rhodococcus ruber DSM 44539, preferentially react with the (S)-enantiomer of the epoxide. Enantioselectivities (enantiomeric ratio, lnE values) show a rather large variation, ranging from almost no (lnE<1) to nearly complete selectivity (lnE>5.3). In addition, the response of the epoxide hydrolases stemming from the four organisms towards structural modifications of the substrate is different. Models for the enantioselectivity (enantiomeric ratio, ln E values) obtained by CoMFA and CoMSIA are of different but reasonable predictive power, e.g., q² _CV=0.701 and r²=0.937 for the CoMFA model of Rhodococcus ruber DSM 43338. Enantiomeric ratios for the test molecules can be well predicted. Plots of steric and electrostatic CoMFA (CoMSIA) fields allow conclusions to be drawn for the choice of the most suitable organism for a specific type of substrate.     

A rare pyridine to pyrrole conversion leading to a side product in epoxide ring opening

A minor side product in a manufacturing batch of the intermediate 4 was observed and separated. The minor side product 5 was purified by preparative HPLC and its structure was determined by the analysis of comprehensive NMR and MS data. The structure of 5 reveals that its mechanism of formation includes a rare conversion of a pyridine moiety to a pyrrole.     

Regioselective ring opening and isomerization reactions of 3,4-epoxyesters catalyzed by boron trifluoride

Efficient ring opening of 3,4-epoxyesters with alcohols to produce 4-alkoxy-3-hydroxyesters and their isomerization into 4-ketoesters using boron trifluoride as the catalyst are presented. Both transformations are simple and efficient methods for the synthesis of the above named synthetically useful compounds.     

Regioselective ring opening in epoxides under the action of amines in water medium

Amino(bis-amino)derivatives of 2-propanol were synthesized by ring opening in epoxides under the action of amines in water medium using environmentally safe methods. The structure of the compounds obtained was established by elemental analysis and the IR, ¹H and ¹³C NMR spectroscopy. It was found that these substances are effective bactericides. They suppress the growth of the sulfate-reducing bacteria and exhibit high anticorrosive properties.     

Synthesis of a 4,5-epoxy-2-cyclohexen-1-one derivative via epoxide ring opening, 1,3-carbonyl transposition and epoxide ring regeneration: a synthetic study on a scyphostatin analogue

A 6-alkyl-4,5-epoxy-6-hydroxy-2-cyclohexen-1-one derivative, a model compound for the hydrophilic moiety of scyphostatin, was stereoselectively synthesized from the Diels-Alder adduct. The key steps were the reductive cleavage of the 4,5-epoxide ring of the epoxidated adduct, the 1,3-carbonyl transposition of the 3-carbonyl group to the C1 position by a Wharton reaction and stereoselective bromination to provide a trans bromohydrin derivative, a precursor to the desired compound. Desilylation of the bromohydrin derivative with TBAF directly gave the target compound.     

Transformed steroids. 133. Synthesis of 20-deoxysteroids with a tetrahydropyran ring E

The synthesis of 20-deoxy compounds — the precursors of the steroid pyranols and pyranones synthesized by the authors previously — has been effected from a steroid 20-ketotetrahydropyran by the hydrogenolysis of the corresponding ethylene dithioketal with Raney nickel. The¹H and¹³C NMR spectra have been studied in detail. Transformations of rings A and B via the epoxide or the 3,5-cyclosteroid have led to 3-acetoxy-16,23-epoxy-5H-21,24-dinorchol-5-en-6-one and 3-acetoxy-5-hydroxy-16,23-epoxy-21,24-dinorchol-5-en-6-one.N. D. Zelinskii Institute of Organic Chemistry, Academy of Sciences of the USSR, Moscow. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 732–735, November–December, 1983.     

Organocatalytic synthesis of beta-alkylaspartates via beta-lactone ring opening

Cinchona alkaloid-catalyzed reaction of ethyl glyoxylate with substituted ketenes, formed in situ, gives disubstituted beta-lactones in moderate yield and high enantiomeric excess. Subsequent azide ring opening, reduction, and ester hydrolysis allows access to chiral beta-alkyl aspartates.