13656-81-0

-

The bicyclic methylenecyclopropane (2) is converted into nezukone (1) in 61percent yield; evidence is presented which suggests heptafulvenes are involved in this conversion.

Disclosed are analogues of hinokitiol, methods for preparing them, and pharmaceutical compositions thereof. Also disclosed are methods for their use in treating iron-related diseases.

An efficient homocoupling of 2-halotropones, to afford 2,2'-bitropones, occurs in toluene at rt in the presence of stoichiometric amounts of [Ni(cod)2] and tris(1-pyrazolyl)methane ligand, in a 1:1 molar ratio. This methodology was extended to aryl halides. Copyright Taylor & Francis Group, LLC.

Pentachloroacetone (1) reacts with several conjugated dienes in the presence of sodium trifluoroethoxide/trifluoroethanol to form cycloadducts of a tetrachlorooxyallyl intermediate 6, mainly in the [4+3] mode. Representative [4+3] cycloadducts, i.e. α,α,α',α'- tetrachlorocycloheptenones 9, have been dehalogenated and dehydrohalogenated, furnishing α,α'-dichlorotropones 15 in high yields.

Nezukone (1) has been synthesized in seven steps from the readily available Δ3-trinorcarene (4).Key features of the sequence used include formation of the bicyclic isomer (2) of compound (1).Base-promoted isomerization of compound (2) followed

Anodic oxidation of cycloheptatrienes has been found to be one of the most powerful key tools for the preparation of a variety of non-benzenoid aromatic compounds such as tropylium salts, tropones, tropolones, 2H-cyclohepta[b]furan-2-ones, and azulenes.

Rhodium(II)-catalyzed decomposition of vinyldiazomethanes in the presence of 1-methoxy-1-buta-1,3-diene leads to annulation products by a tandem cyclopropanation/Cope rearrangement sequence.The resulting cycloheptadienes are r

The preparation of 4-alkyl (or aryl) tropones has easily been accomplished by the anodic oxidation of 1-methoxy-4-alkyl (or aryl) cycloheptatrienes which where synthesized by the regioselective addition of alkyl or aryl lithium to 3-position of 7,7-dimethoxycycloheptatriene followed by the thermal 1,5-hydrogen shift of the resulting 3-methoxy-7-alkyl (or aryl) cycloheptatrienes.

The Rh-catalyzed reaction of 1,3-butadiene with ethyl 3-diazopyruvate leads, inter alia, to a dihydro-oxepinecarboxylate whose oxidation and functional-group manipulation produce salicylates.Wittig reactions on the acylcyclopropane accompanying the dihydrooxepine yields acrylates whose pyrolyses afford cycloheptadienecarboxylates.Oxidation and functional-group transformation produces the natural tropone, nezukone.

An acetonitrile solution of acetylene and 3-methylcyclopent-2-enone (4) was irradiated with Pyrex-filtered light from a mercury lamp to give 5-methylbicyclohept-6-en-2-one (6) and 6-methyl-tricyclo2,7>heptan-3-one (8).These were easily separated and when heated under reflux in ButOH with SeO2 gave the 4-methyltropone valence-tautomer 5-methylbicyclohept-3,6-dien-2-one (10) and 4-methyltropone (12), respectively, the latter in 20percent overall, unoptimized yield.Similar reactions with 3-isopropylcyclopent-2-enone (5) in the place of (4) led to the natural troponoid 4-isoproyltropone (nezukone) (13).

Application of the polybromo ketone-iron carbonyl reaction to natural product synthesis is summarized.The general synthesis of tropane alkaloids has been achieved via the reductive cyclocoupling of sym-tetrabromoacetone with N-methoxycarbonylpyrrole as the key step.Ready availability of 8-oxabicyclooct-6-en-3-one from the tetrabromoacetone and furan has opened a new, efficient entry to natural C-nucleosides including pseudouridine, pseudocytidine, and showdomycin.The artificial analogues such as 2-thiopseudouridine, 6-azapseudouridine, pseudoisocytidine, etc., are also obtainable.The oxabicyclic ketones bearing an isopropyl substituent at the appropriate position serve as intermediates for the synthesis of naturally occurring troponoids, nezukone, α-thujaplicin, and hinokitiol (β-thujaplicin).Carbocamphenilone and camphenic acid have been prepared through the reaction of 1,1,3-tribromo-3-methylbutan-2-one and cyclopentadiene.The cyclocondensation of α,α'-dibromo ketone and a styrene derivative leads to the single-step synthesis of α-cuparenone. 1,3-Dibromo-3,7-dimethyloct-6-en-2-one derived from nerol (or geraniol) undergoes the biogenetic-type double cyclization.The iron carbonyl-assisted intramolecular cyclocoupling gives camphor accompanied by other monoterpenic ketones.A mixture of campherenone and epicampherenone has been obtained from related dibromo ketone prepared from farnesols.The hetero reaction by use of dibromo ketones and N,N-dimethylcarboxamides, forming 3 (2H)-furanones, is employable for the preparation of muscarine alkaloid derivatives.

Nerol was cyclized to terpinyl chloride or bromide in the presence of TiX4-PhNHMe (1:1) complex (I, X=Cl, Br) in dichloromethane at -23 deg C, geraniol being converted into geranyl halide by simple halogenation.Terminally modified derivatives YCH2C(Me)=CHCH2CH2CMe=CHCH2OH (Y=SiMe3, SnBu3) of (2Z,6E) configuration were cyclized by treatment with I to afford limonene in high yields and 100percent selectivity.Cyclization of (2Z) isomers of CH2=CR-CH2CH2CMe=CHCH2OH (R=H, Me, Cl) produced seven-membered carbocyclic products in fair yields.The novel procedure has been utilized in the synthesis of nezukone from (2E)-3-isopropyl-2,6-heptadien-1-ol involving five steps.

Photooxygenation of 7-substituted cycloheptatrienes, including the Me, Et, iPr, Ph, CN, COOMe, COOEt, and CONH2 groups was studied, and several products among the tropilidene-type (1 and 2) and norcaradiene-type (3 and 4) endoperoxides, o-substituted benzaldehydes (5), diepoxides (6 and 7), and ketoalcohols (8) were obtained.Mechanism of the formations of the products was discussed.Thermal isomerization of the endoperoxides (1, 3 and 4) to the corresponding diepoxides (10, 6 and 7), and the reaction of the endoperoxides (1 and 3) with triethylamine were examined.