Polyfluoro-compounds based on the cycloheptane ring system. Part 8. Pentafluorotropolone and other hydroxy- and methoxypolyfluorotropones

Hexafluorotropone with aqueous sodium hydroxide afforded 2-, 3-, and 4-hydroxypentafluorotropone in the respective proportions, 15:65:20. The tropolone was isolated pure by chelation, and the 3-hydroxide by salt formation, but the 4- isomer was only obtained in admixture with the 3-hydroxide. Each product gave the corresponding methyl tropyl ether on treatment with diazomethane. Treatment of hexafluorotropone with sodium methoxide under mild conditions gave a mixture, but with predominant formation of the 3-methoxide or the 3,6- dimethoxide: exhaustive methoxylation gave hexamethoxytropone. Reactions with other nucleophiles did not give tractable products.     

Polyfluoro-compounds based on the cycloheptane ring system. Part 6. Bicyclic compounds derived from nonafluorocyclohepta-1, 3-dienes and from octafluorocyclohepta-1, 3, 5-triene

1H-, 2H-, and 5H- Nonafluoro- and 1H,4H-octafluoro-cyclohepta-1,3 diene afforded the corresponding H-substituted polyfluorobicyclo(3, 2, 0)- hept-6-enes by cross-ring bond formation between positions 1 and 4. Octafluorocyclohepta-1, 3, 5-triene similarly gave octafluorobicyclo- (3,2,0)hepta-2,6-diene. By passage over cobalt(III) fluoride at 100°C, the 1H-bicyclo-6-ene gave 1H-undecafluorobicyclo(3, 2, 0)heptane and thence the corresponding fluorocarbon. The bridgehead hydrogen of the 1H- bicyclo-ane was sufficiently acidic to exchange for deuterium with deuterium oxide, alone or containing some potassium hydroxide, but longer exposure to aqueous potash gave decafluorobicyclo(3, 2, 0)hept-1(5)-ene. This was oxidised by potassium permanganate in acetone to give decafluoro-1, 5- dihydroxy-8-oxabicyclo(3, 2, 1)octane (hydrated), which underwent methylation by diazomethane to the corresponding 1,5-dimethoxy-compound. A Diels-Alder reaction between ethylene and 1H-nonafluorocyclohepta-1, 3- diene afforded 1H,8H,8H,9H,9H-nonafluoro-bicyclo(3,2,2)non-6-ene. Cobalt (III) fluoride at 300°C converted this principally to 1H-pentadecafluoro- bicyclo(3,2,2)nonane. The bridgehead hydrogen of this was exchanged for deuterium using deuterium oxide alone or containing potassium hydroxide. However, dehydrofluorination occurred with bases, though an olefin could not be isolated.     

Substitution in the hydantoin ring. Part IX. N-cyanohydantoins

The N₁-and N₃-cyanohydantoins, a new series of derivatives, were prepared by reaction of the parent hydantoin with a base and a cyanogen halide. Analysis of ir, pmr, and mass spectral data allowed the assignment of ring position-3 to the cyano group in derivatives IIa,b of 1,3-unsubstituted hydantoins. 3-Cyanohydantoins can transfer the cyano substituent to strong nucleophiles via an addition-elimination process.     

Thermal Valence Rearrangements of Heterocycles. Part 2. A new synthetic approach towards the indole ring system

A new synthetic approach towards the indole ring system is described. When dimethyl 1-methyl-2-oxa-1-aza-spiro[4.5]dec-3-ene-3,4-dicarboxylate ( 6 ) was refluxed in toluene, the previously known dimethyl 4,5,6,7-tetra-hydro-1-methyl-1H-indole-2,3-dicarboxylate ( 7 ) was obtained in 71% yield, via a 2,3-dihydroisoxazole-pyrrole rearrangement. After treatment with DDQ , the tetrahydro analogue 7 was converted to the corresponding dimethyl 1-methyl-1H-indole-2,3-dicarboxylate ( 8 ).     

Organic Stereochemistry. Part 7

This review continues a general presentation of the principles of stereochemistry with special emphasis on the biomedicinal sciences. Here, we discuss and illustrate the phenomenon of substrate stereoselectivity in biochemistry (endogenous metabolism) and principally in xenobiochemistry or drug metabolism. The review begins with an overview of the stereoselective processes occurring in the biomedicinal sciences. The general rule is for distinct stereoisomers, be they enantiomers or diastereoisomers, to elicit different pharmacological responses (Part 5), to a lesser extent be transported with different efficacies (Part 5), and to be metabolized at different rates (this Part). In other words, biological environments discriminate between stereoisomers both when acting on them and when being acted upon by them. The concept of substrate stereoselectivity describes this phenomenon in endogenous biochemistry and xenobiotic metabolism, as discussed and illustrated in the present Part. The sister concept of product stereoselectivity will be presented in Part 8.     

Synthesis of the ABC ring system of azaspiracid. 1. Effect of D ring truncation on bis-spirocyclization

[reaction: see text] Synthesis of a spirocyclization precursor with a truncated D ring has been accomplished. Subsequent bis-spirocyclization induced the formation of equal amounts of the natural transoidal 10R,13R bis-spirocycle and its cisoidal 10R,13S epimer under an apparent thermodynamically controlled process.     

A new tripodal ligand system based on the iminophosphorane functional group. Part 1: Synthesis and characterization

Two tripodal alcohols, viz., 1,1,1-tris(hydroxymethyl)ethane and α,α,α-tris(hydroxymethyl)toluene were converted by an efficient multi-step pathway involving azide formation into the corresponding tris(iminophosphorane) scaffolds bearing cyclopentyl (Cp) or phenyl groups on their phosphorus atoms, R-C(CH₂-NPR′₃)₃ (R=Me or Ph, R′=Cp or Ph). The synthesis of some representative transition-metal complexes of Cu(I), Cu(II), Ni(II), and Pd(II) bearing these new tridentate ligands is also reported.     

Silylcuprates from allene and their reaction with alpha,beta-unsaturatedd nitriles and imines. Synthesis of silylated oxo compounds leading to cyclopentane and cycloheptane ring formation

The silylcupration of allenes and the subsequent capture of the intermediate cuprate with alpha,beta-unsaturated nitriles is reported. The influence of the substitution of the nitrile, the nature of the silylcopper species, and the temperature on the selectivity of the reaction is studied. An interesting diaddition process was observed (1,2-addition and 1,4-addition), leading to oxo compounds which simultaneously have an allylsilane and a vinylsilane group. The different reactivity of these two units has been employed in the intramolecular allylsilane-terminated cyclization of these adducts, where the vinylsilane moiety remains unchanged. To shed some light on the reaction pathway, the behavior of alpha,beta-unsaturatedd imines was also checked and a new and convenient way for cycloheptane annulation presented. In light of the former results a feasible mechanism is proposed.     

Microbial metabolism. Part 7 : Curcumin

Microbial metabolism of the cancer chemopreventive agent, curcumin [(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione] (1) with Pichia anomala (ATCC 20170) yielded four major metabolites, 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3-one (2), 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)heptan-3-one (3), 1,7-bis(4-hydroxy-3-methoxyphenyl)heptan-3,5-diol (4), 5-hydroxy-1,7-bis(4-hydroxyphenyl)heptane-3-one (5) and two minor products, 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)heptane-3,5-diol (6) and 1,7-bis(4-hydroxyphenyl)heptane-3,5-diol (7). The structures of compounds 2-5 were established on the basis of spectroscopic data. Compounds 6 and 7 were assigned tentative structures.     

Spectra and structure of small ring compounds: Part XXXVIII. Cyclobutanol

The Raman spectrum of gaseous cyclobutanol has been recorded and the far infrared spectrum of the gas has been obtained at a resolution of 0.5 cm^?1. At least six Q-branches arising from the low frequency ring-puckering motion have been observed and assigned on the basis of a potential of the form V(X) = (6.32 ± 0.21) × 10⁵X⁴?(4.18 ± 0.04) × 10⁴X²+ (8.81 ± 1.20) × 10³X³ with a reduced mass of 170 amu. An energy difference between the equatorial and axial forms was found to be 50–150 cm^?1 with the equatorial being more stable and a barrier of 700–900 cm^?1 was found for the interconversion. Three O-H stretching modes were observed in the Raman spectrum. It is concluded that the O-H moiety has both the gauche and trans conformations present in the equatorial form but only the gauche conformer is present in the axial form of the ring. Three O-H torsional modes were observed at 244 (trans conformer), 226.5 and 181.5 cm^?1 (gauche conformer) for the equatorial form and one O-H torsion at 237.5 cm^?1 (gauche conformer) for the axial form. The potential function governing the O-H torsional motion for the equatorial form was found to be V₁ = 280 ± 7 cm^?1 (800 cal mole^?1) and V₃ = 425 ± 3 cm^? (121.5 cal mole^?1) with the trans conformer being more stable than the gauche by approximately 206 cm^?1 (589 cal mole^?). The barriers to trans-gauche and gauche-gauche interconversion have essentially the same values, 500 cm^?1 (1430 cal mole^?1).     

Reactions involving fluoride ion. Part 34. A novel ring contraction

The CsF-catalysed isomerisation of perfluoro-1,1′-bis-1,3-diaza- cyclobex-2-enyl (1) in the absence of solvent gave perfluoro-4-methyl- 1,2,5,7-tetraazatricyclo[3.3.1.O^2.6]undec-4-ene (2) via intramolecular 1,3-attack at a saturated position in an intermediate nitrogen anion.     

Azasteroids. v. approaches to the 14,16-diazasteroidal ring system

Making use of Reissert compound II and Reissert compound analogue VI, benzo [f]quinoline has been converted into the 14,16-diazasteroidal ring system. A number of reactions in this ring system are discussed.     

Synthetic studies toward pectenotoxin 2. Part II. Synthesis of the CDE and CDEF ring systems

A convergent synthesis of the CDE and CDEF ring systems of pectenotoxin-2 from C and F ring precursors is described.     

Synthetic approaches toward ecteinascidins. Part 2. Preparation of the ABCDE ring system of ecteinascidins having characteristic substituents in both benzene rings

A synthesis of an advanced ABCDE ring system (24c) having characteristic substituents in both benzene rings of ecteinascidin marine natural products is described based on our model studies.     

Studies on tellurium-containing heterocycles. Part 22. Tellurazepine ring system: preparation of 1,5-benzotellurazepin-4-ones and their conversion into fully unsaturated 1,5-benzotellurazepines

The treatment of o-iodopropiolanilides (12), which were easily prepared from o-iodophenylisocyanate (11) and ethynylmagnesium bromide, with sodium hydrogen telluride resulted in the intramolecular ring closure of the presumed phenyltellurol intermediates (13) to a triple bond to give the 1,5-benzotellurazepin-4-ones (14) as the sole characterized products. The obtained amides (14) were easily converted into fully unsaturated lactim 4-methoxy-1,5-benzotellurazepines (18) by treatment with trimethyloxonium tetrafluoroborate. Decomposition by thermolysis of the 4-methoxyazepinenes (18) afforded the 4-methoxyquinolines (19) with extrusion of a tellurium atom.     

Novel heterocycles. Synthesis of the 2,4,3-benzodiazaphosphepine ring system

Novel alkyl (1,2,4,5-tetrahydro-3H-2,4,3-benzodiazaphosphepin-3-yl)carbamate-P-oxides ( 7 ) were synthesized by cyclization of the corresponding dichlorophosphinylcarbamates ( 5 ) with α,α'-diamino-o-xylene ( 6 ). A steric limitation in the synthesis of analogs is discussed.     

The structure of the cyclooctadecane ring system. 1,10-Cyclooctadecanedione

The crystal structure of the title compound was determined by X-ray crystallography and solved by direct methods; the molecule has C_2h symmetry. The carbon atoms are arranged in a diamondoid lattice, but not of the rectangular type that might have been expected. The dipole moment for the conformation found in the crystal is zero, while the observed dipole moment of the compound in solution is 2.78 D. Molecular mechanics calculations were carried out on several of the large number of possible conformation. Of those studied, the conformation found in the crystal had the lowest energy.