Opening of the Macrocyclic Ring in 5,10:8,9-Disecosteroids ( = Steroklastanes)

Catalytic hydrogenation of the Δ³-unsaturated (9R,10 R)- and (9S,10 S)-epoxyenol lactones 3a, b. , and 4a, b. , respectively, affords, in addition to the expected saturated epoxylactones 5a, b and 7a, b , also open-chain products, i.e. the diastereoisomeric (9R,10R)- and (9S,10S)-9,10-expoxy-8-oxo-4,5-secosteroklastan-5-oic acids 6a, b. and 8a, b. Alkaline hydrolysis of the lactone ring of compounds 5 and 7 and subsequent acetylation of the corresponding hydroxy derivatives give as the major products the open-chain, diasteroisomeric (9R,10R)- and (9S,10S)-4-acetoxy-9,10-epoxy-methyl esters 9a, b and 11a, b , respectively, and, but only in the androstane series, the tetrahydropyran derivatives 10a and 12a , as the minor components.     

Tautomeric and conformational equilibria of γ-lactones derived from (3,5-dibromo-1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl)acetic acid

Tautomeric transformation of (3,5-dibromo-1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl)acetic acid into previously unknown stereoisomeric γ-lactones, (3aS*,7S*,7aR*)- and (3aS*,7R*,7aR*)-5,7-dibromo-3ahydroxy-3,3a,7,7a-tetrahydro-1-benzofuran-2,6-diones, was revealed by ¹H NMR spectroscopy. The concentration of the acid tautomer increases as the solvent polarity rises. The ability of the cycloxexene ring in the lactones to undergo inversion in solution is determined by orientation of the bromine atom on C⁷.     

Copper-catalyzed α-aminoxylation of 1,3-dicarbonyl compounds with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) via an aerobic oxidative sp C–H bond activation

A facile and direct synthetic method for the construction of alkoxyamine derivatives through copper-catalyzed aerobic oxidative activation of sp³ C–H bond was developed in good to excellent yields (75−95%), by treating the readily available 1,3-dicarbonyl compounds with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and its derivatives. This method was also successfully applied to the preparation of quaternary α-fluorinated α-hydroxyl acid derivatives.     

Heterocyclic studies—XXII. Mass spectra of some 3-hydroxypteridin-4-ones

Mass spectra of 3-hydroxypteridin-4-one and five of its mono-and di-methyl derivatives are recorded. Fragmentation of the non-methyl compound (I; R¹  R²  R³  H) occurred mainly by successive losses of NO, CO, HCN and HCN. Changes in m/e values of the major peaks with methyl-substitution pattern in the derivatives were consistent with the proposed fragmentation pattern. Several minor fragmentation pathways were also observed but all involved an initial loss from the oxygen containing ring.     

Lactone Synthesis by Enantioselective Orthogonal Tandem Catalysis

In this work, we report enantioselective orthogonal tandem catalysis for the one pot conversion of Meldrum's acid derivatives and alkynes into δ‐lactones. This new transformation, which resembles a formal [4+2] cycloaddition with concomitant decarboxylation and loss of acetone, proceeds in high yields and excellent enantioselectivity (up to 99 % ee) over a broad substrate scope. The products are densely functionalized and ripe for further transformations, as demonstrated here by both ring‐opening reactions and reduction to saturated lactones. It was discovered that a new and serendipitously formed Ag^I‐Me‐StackPhos complex efficiently catalyzes the highly selective 6‐endo‐dig cyclization, completely reversing the regiochemistry that has been previously reported in related systems. More generally, in this study we identify a pair of compatible catalysts for alkyne difunctionalization that operate concurrently, which enable the alkyne to act as both a nucleophile and an electrophile in sequential one‐pot transformations.     

Observations on the copper(II) catalyzed reactions of enaminones and dimethyl diazomalonate

The Cu(acac)₂ catalyzed reactions of dimethyl diazomalonate with enaminones yielded 1,5-cyclization and α-CH insertion products. In the case of anilino derivatives (R¹ or R² = Ph), products resulting from an unusual insertion to the benzoyl ring dominated the reaction.     

Stereochemistry and 13C NMR investigation of 9-halotetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones

It was shown that the halogen atom occupies the quasi-axial position in the predominant conformer of the 9-halo derivatives of tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones. When R³ = Me, the conformational equilibrium is determined by the latter substituent which is always quasi-axial. The effects of the methyl group and the halogen atoms on the ¹³C chemical shifts (SCS values) were used for the identification of cis and trans isomers. Interesting non additivity of substituent effects was found in derivatives bearing quasi-axial substituents at C-6 and C-9: and this was caused by the ring flattening.     

N-H⋯S hydrogen bonding motifs in crystalline solids of 1,2,4-triazole-5-thiones: Application of the Cambridge Structural Database. R 2 2 (8) ring motif

A database study on the N-H?S hydrogen bonding ring motif (R ₂ ² (8)) for 1,2,4-triazole-5-thiones is reported. The R ₂ ² (8) ring is one of the most general ring motifs observed in the crystallographic literature, however, up to now the ring synthon built by the N-H?S interaction has not been particularly described. Probably, in multi-heteroatom systems, other structure-determining stronger interactions may take precedence over weaker N-H?S interactions. On the other hand, in recent years, considerable importance has been given to structures determined through N-H?S interactions. It is also common in the crystals of 1,2,4-triazole-5-thione derivatives.     

Metabolism of Deuterated Isomeric 6,7‐Dihydroxydodecanoic Acids in Saccharomyces cerevisiae – Diastereo‐ and Enantioselective Formation and Characterization of 5‐Hydroxydecano‐4‐lactone (=4,5‐Dihydro‐5‐(1‐hydroxyhexyl)furan‐2(3H)‐one) Isomers

The chemical synthesis of deuterated isomeric 6,7‐dihydroxydodecanoic acid methyl esters 1 and the subsequent metabolism of esters 1 and the corresponding acids 1a in liquid cultures of the yeast Saccharomyces cerevisiae was investigated. Incubation experiments with (6R,7R)‐ or (6S,7S)‐6,7‐dihydroxy(6,7‐²H₂)dodecanoic acid methyl ester ((6R,7R)‐ or (6S,7S)‐(6,7‐²H₂)‐ 1 , resp.) and (±)‐threo‐ or (±)‐erythro‐6,7‐dihydroxy(6,7‐²H₂)dodecanoic acid ((±)‐threo‐ or (±)‐erythro‐(6,7‐²H₂)‐ 1a , resp.) elucidated their metabolic pathway in yeast (Tables 1–3). The main products were isomeric ²H‐labeled 5‐hydroxydecano‐4‐lactones 2 . The absolute configuration of the four isomeric lactones 2 was assigned by chemical synthesis via Sharpless asymmetric dihydroxylation and chiral gas chromatography (Lipodex ^® E). The enantiomers of threo‐ 2 were separated without derivatization on Lipodex ^® E; in contrast, the enantiomers of erythro‐ 2 could be separated only after transformation to their 5‐O‐(trifluoroacetyl) derivatives. Biotransformation of the methyl ester (6R,7R)‐(6,7‐²H₂)‐ 1 led to (4R,5R)‐ and (4S,5R)‐(2,5‐²H₂)‐ 2 (ratio ca. 4 : 1; Table 2). Estimation of the label content and position of (4S,5R)‐(2,5‐²H₂)‐ 2 showed 95% label at C(5), 68% label at C(2), and no ²H at C(4) (Table 2). Therefore, oxidation and subsequent reduction with inversion at C(4) of 4,5‐dihydroxydecanoic acid and transfer of ²H from C(4) to C(2) is postulated. The 5‐hydroxydecano‐4‐lactones 2 are of biochemical importance: during the fermentation of Streptomyces griseus, (4S,5R)‐ 2 , known as L‐factor, occurs temporarily before the antibiotic production, and (?)‐muricatacin (=(4R,5R)‐5‐hydroxy‐heptadecano‐4‐lactone), a homologue of (4R,5R)‐ 2 , is an anticancer agent.     

The Reactivity of Cyameluric Chloride C6N7Cl3 towards Phosphines and Phosphine Oxides

Organophosphines (R₂PH) and phosphineoxides (R₂OPH) show a very high reactivity towards cyameluric chloride C₆N₇Cl₃. For example, 2,4,6‐trisdiphenylphosphino‐tri‐s‐triazine ( 1 ) forms quantitatively within a few seconds. Tris‐diphenylphosphinsulfide‐s‐heptazine ( 2 ) was obtained by reaction of 1 with sulfur. These compounds represent a new class of s‐heptazine derivatives which tend, unlike their s‐triazine analogues, to decompose in solution. 1 forms crystals with nitromethane, which were analysed by single‐crystal X‐ray diffraction. The nitromethane molecules fill the gaps in the crystal lattice supported by hydrogen bonds, C–H ··· π ring, and N–O ··· π ring interactions. All compounds were characterized by ¹H, ¹³C and ³¹P NMR and vibrational (FT‐IR, Raman) spectroscopy. The thermal stability of selected derivatives was measured by TG, indicating surprisingly low thermal decomposition temperatures.     

Investigation of the grewe codeine method. Attempts to achieve a practical synthesis

The svnthesis of 1-(2′-bromo-4′-methoxy-5-hydroxybenzyl)-6-keto-^Δ4a-5-decahydroisoquinoline (IX) is described. Efforts to cyclize this intermediate or its N-acyl derivatives in acidic media to morphinan products were unsuccessful. The presence of the para-bromine blocking group apparently exerts a deactivating influence on the phenolic ring. 1-(3′,5′-Dihydroxy-4′-methoxybenzyl)-6-methoxy-1,2,3,4,5,8-hexahydroisoquinoline (XVIII) was readily cyclized to 2-hydroxydihydronorthebainone. However, attempts to remove the 2-hydroxy group and subsequent conversion to dihydronorcodeine were unrewarding.     

Behavior of 1,1-diphenyl-2,5-dihydrophospholium salts toward bases: Ylide formation or ring opening

Efficient procedures are described leading to pure 3,4-R¹, R²-substituted 1,1-diphenyl-2,5-dihydrophospholium salts (R¹ = R² = CH₃, H; R¹ = CH₃, R² = H). Their behaviors toward bases such as nBuLi and tBuOK in THF or DMSO have been examined. According to the nature of the substituents R¹ and R², the complete monodeprotonation of these salts leads either to the corresponding pure five-membered cyclic ylide (and, in some cases, its prototropic isomer) or to a dienylphosphine resulting from a ring opening. The reactivity of the 3,4-dimethyl-disubstituted salt was especially studied. The corresponding monoylide functions as a good Wittig reagent, allowing stereoselective access to interesting alkadienylphosphine oxides and subsequently to trienes. However, in the presence of alkylating electrophiles, it reacts under an open dienylphosphine form giving rise to P-alkylated phosphonium salts. Nevertheless, this monoylide does not undergo further deprotonation into the corresponding cyclic diylide. Most of the synthetisized derivatives are original. © 1996 John Wiley & Sons, Inc.     

Synthesis of enantiomerically pure α-amino-β-hydroxy-cyclobutanone derivatives and their transformations into polyfunctional three- and five-membered ring compounds

Ketenes readily cycloadded to (R)-tert-butyldihydrooxazole 2a-d to yield enantiomerically pure bicyclic cyclobutanones. The cycloadditions proceeded with unusual regiochemistry giving predominantly or exclusively protected α-amino-β-hydroxycyclobutanone derivatives. The adducts could be converted into a variety of interesting enantiopure intermediates equipped with many functional groups: α-amino-β-hydroxy cyclopropane carboxylic acid derivatives, α-amino-β-hydroxy succinic acid derivatives, α-amino-β-hydroxy lactones and lactams derivatives.     

Rearrangement products of some 1R,4R-2-arylidene-p-menthan-3-ones in acidic media, their structures, and conformational analysis

1R,4R-2-(4-Phenylbenzylidene)-p-menthan-3-one in acidic media undergoes rearrangement with migration of the exocyclic double bond to the cyclohexane ring to form three 2-(4-phenylbenzyl) derivatives ofp-menthen-3-ones. The reaction products differ in the location of the endocyclic double bond (Δ¹ or Δ⁴) and in the configuration of the new chiral C(2) center in the resultingp-menth-4-en-3-ones. The configurations of the 1R,2R- and 1R,2S-2-(4-phenylbenzyl)-p-menth-4-en-3-ones were established based on analysis of their¹H NMR spectra in combination with calculations by molecular mechanics. The molecular conformations of these compounds as well as of some racemic 2-benzyl-p-menth-1-en-3-one derivatives were studied.     

Theoretical studies on QSAR and mechanism of 2‐indolinone derivatives as tubulin inhibitors

The theoretical studies on three‐dimensional quantitative structure activity relationship (3D‐QSAR) and action mechanism of a series of 2‐indolinone derivatives as tubulin inhibitors against human breast cancer cell line MDA‐MB‐231 have been carried out. The established 3D‐QSAR model from the comparative molecular field analysis (CoMFA) shows not only significant statistical quality but also predictive ability, with high correlation coefficient (R² = 0.986) and cross‐validation coefficient (q² = 0.683). In particular, the appropriate binding orientations and conformations of these 2‐indolinone derivatives interacting with tubulin are located by docking study, and it is very interesting to find that the plot of the energy scores of these compounds in DOCK versus the corresponding experimental pIC₅₀ values exhibits a considerable linear correlation. Therefore, the inhibition mechanism that 2‐indolinone derivatives were regarded as tubulin inhibitors can be theoretically confirmed. Based on such an inhibition mechanism along with 3D‐QSAR results, some important factors improving the activities of these compounds were discussed in detail. These factors can be summarized as follows: the H atom adopted as substituent R₁, the substituent R₂ with higher electropositivity and smaller bulk, the substituents R₄–R₆ (on the phenyl ring) with higher electropositivity and larger bulk, and so on. These results can offer useful theoretical references for understanding the action mechanism, designing more potent inhibitors, and predicting their activities prior to synthesis. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009     

INDO MO calculations of the electronic structures of pyrolle,imidazole, and derivatives

INDO MO calculations on a series of N-substituted pyrroles and imidazoles have been analysed for substituent effects. Some of the basic characteristics of the σ_I and σ_R⁰ parameters are reflected in the calculated electron densities of the compounds studied. For example, good correlations are obtained between Δqσ ^N(1)/ΣΔqσ parameters and σ_I for the R substituted compounds, as well as between ΣΔqπ values and σ_R⁰ for the + R derivatives. The + R substituents lead to an increased localization of the π-bonds, whereas R substituted derivatives show an increased delocalization, i.e., the π-bond orders across C(2)C(3) [or C(2)N(3)] and C(4)C(5) decrease and those across other bonds in the ring increase.     

Rapid Synthesis of Alkoxyamine Hydrochloride Derivatives from Alkyl Bromide and N,N′-Di-tert-butoxycarbonylhydroxylamine [(Boc)2NOH]

The conventional route to alkoxyamine hydrochloride derivatives is by reaction of alkyl bromides with N-hydroxyphthalimide or N-hydroxysuccinimide followed by addition of hydrazine and HCl. Transformation of an alkyl bromide to the corresponding alkoxyamine hydrochloride can be accomplished more rapidly in good yields without using hazardous hydrazine by reaction of (Boc)₂NOH (N,N′-di-tert-butoxycarbonylhydroxylamine) and alkyl bromide followed by addition of HCl. Alkoxyamine hydrochlorides are powerful reagents in organic synthesis that can be used to synthesize alkoxyimino derivatives after condensation with a ketone or aldehyde.     

Hydride-transfer reactions of [(h5-cyclohexadienyl)(h5-cyclopentadienyl)iron] alkylium ions

In CF₃ CO₂ H solution, (h⁵-cyclohexadienyl)(h⁵-cyclopentadienyl)iron derivatives containing an R¹ R² C(OH) substituent attached either to the cyclopentadienyl ring or to C(1) of the cyclohexadienyl ligand are converted into (h⁶-arene)(h⁵-cyclopentadienyl)iron cations by hydroxyl loss and hydride migration.     

Extended conjugated mesogens: synthesis and mesomorphic properties of H-shaped mesogens based on 3,3ʹ,5,5ʹ-tetrasubstituted 2,2ʹ-bithiophene with oligo(1,4-phenyleneethynylene) arms

A new class of extended conjugated mesogens, namely H-shaped mesogens based on 3,3?,5,5?-tetrasubstituted 2,2?-bithiophene with oligo(1,4-phenyleneethynylene) arms, have been synthesised, and the relationships between molecular structures and mesomorphic properties investigated. Tetraalkyl, tetraalkoxy and dialkyldialkoxy derivatives, [R¹C₆H₄CCC₆H₂(C₂H₅)₂CC]₂[R²C₆H₄CCC₆H₂(C₂H₅)₂CC]₂C₈H₂S₂ where R¹ and R² = alkyl and alkoxy chains of different lengths, exhibit nematic phases. The length, number and position of the terminal chains strongly affect the mesomorphic properties. The tetraalkyl derivatives in which R¹ = R² = pentyl to heptyl exhibit enantiotropic mesophases, whereas the derivatives with octyl or nonyl chains exhibit monotropic mesophases. The tetraalkoxy derivatives in which R¹ = R² = pentyloxy to nonyloxy all exhibit enantiotropic nematic phases. The mesophase range increases with increasing alkoxy chain length, except that the octyloxy and nonyloxy derivatives have almost the same temperature range. The dialkyldialkoxy derivatives in which R¹ = alkyl; R² = alkoxy and in which R¹ = alkoxy; R² = alkyl (R¹ and R² = heptyl, nonyl, hexyloxy or nonyloxy) exhibit enantiotropic mesophases. The derivatives in which R¹ = alkoxy have a significantly lower crystal–nematic transition temperature than the corresponding derivatives (R² = alkoxy), although the two types of derivatives have a similar nematic–isotropic transition temperature.     

Azulen als Brückenligand in Zweikernigen Paramagnetischen Nickelkomplexen — Synthese und Eigenschaften

Azulene as Bridging Ligand in Dinuclear Paramagnetic Complexes of Nickel — Synthesis and Spectroscopic Properties The reactivity of dianions of several alkyl substituted azulene derivates towards half sandwich complexes [(η⁵‐C₅R_1‐5)Ni (η²‐acetylacetonat)] (R = H, Me, Ethyl) has been studied and leads to the formation of paramagnetic dinickel complexes of the nonbenzenoid hydrocarbon azulene. From these studies it is found that the five membered ring system of the azulene ligand is coordinated in a nickelocene like fashion, the seven membered ring system in a halfopen metallocene type fashion. Therein the seven membered azulene ring unit is complexed in a pentadienyllike fashion. This corresponds to cyclovoltammetric studies in which a correlation with the potentials for alkylated nickelocene derivatives is found.