Homo- and hetero-[3]rotaxanes with two pi-systems clasped in a single macrocycle

Here we present the first synthesis of a [3]rotaxane with two dumbbell components threaded through a single gamma-cyclodextrin macrocycle. This synthesis is carried out in two steps: first one dumbbell is synthesized threaded through the macrocycle to give a [2]rotaxane, then a second dumbbell is synthesized through the remaining cavity of the [2]rotaxane. We have synthesized a hetero- [3]rotaxane with one stilbene and one cyanine dye threaded through gamma-cyclodextrin, which exhibits quantitative energy transfer between the two encapsulated dyes. The stilbene [2]rotaxane intermediate in this synthesis has a remarkably high affinity for suitably shaped hydrophobic guests in aqueous solution, facilitating the synthesis of [3]rotaxanes and suggesting possible applications in sensors.     

Effect of an inhibitor of squalene epoxidase, NB-598, on lipid metabolism in Hep G2 cells.

NB-598, a potent inhibitor of squalene epoxidase, inhibited cholesterol synthesis from [14C]acetate and induced intracellular squalene accumulation in Hep G2 cells. NB-598 inhibited cholesterol synthesis from [14C]acetate, [3H]mevalonate, and [3H]squalene, but not from [3H]2,3-oxidosqualene in Hep G2 cells. It reduced cholesterol ester synthesis remarkably in the absence of exogenous cholesterol. This compound did not have any effect on the synthesis of ubiquinone and dolichol. When Hep G2 cells were prelabeled with micellar [3H]cholesterol, NB-598 did not affect the excretion of bile acid incorporated from [3H]cholesterol. However, NB-598 decreased the secretion of free and esterified cholesterol, triacylglycerol, and phospholipids, and increased the secretion of squalene. NB-598 is thought not only to inhibit cholesterol synthesis, but also to inhibit the secretion of lipids.     

Synthesis of amine, halide, and pyridinium terminated 2-alkyl-p-tert-butylcalix[4]arenes

The synthesis of calix[4]arenes with functional groups tethered to a single methylene bridge has been explored. Mono-lithiated calix[4]arenes react with 1,ω-bromochloroalkanes to give 2-(ω-chloroalkyl)-calix[4]arenes, which function as key intermediates in the synthesis of a variety of tether-functionalized calix[4]arenes. Subsequent reactivity of these chloroalkyl species has allowed for successful synthesis of 2-(ω-iodoalkyl)-calix[4]arenes, 2-(ω-pyridiniumalkyl)-calix[4]arenes, and 2-(ω-aminoalkyl)-calix[4]arenes. This latter group of amine-terminated calix[4]arenes are especially significant as they may serve as useful entries to a wide range of subsequent chemistry, including metal coordination or attachment to a solid support. Both alkyl and aryl amines have been incorporated at the end of the tether, and a 2,6-diisopropylaniline derivative has been analyzed by X-ray diffraction.     

A new approach to construct full-length glycosylphosphatidylinositols of parasitic protozoa and [4-deoxy-Man-III]-GPI analogues

A new [2 + 2 + 2] approach to construct GPI molecules through the efficient synthesis of glucosamine-inositol and tetramannose intermediates led to a total synthesis of a GPI-anchor of Trypanosoma cruzi, and also afforded a key intermediate for the synthesis of valuable [4-deoxy-Man-III]-GPI analogues.     

From propargylic biscarbonate to diaryl[n]dendralenes

An efficient cross-coupling reaction using a low cost carbon-supported palladium (Pd/C) catalyst for the synthesis of cross-conjugated compounds, diaryl[n]dendralenes, has been developed. The reaction of a propargylic biscarbonate with phenylboronic acid using Pd/C and phosphine ligand (S-Phos) gave 2,3-diphenyl[2]dendralene in high yield. We found that Pd/C was an effective catalyst for the synthesis of dialyl[n]dendralenes. The synthesis of various dendralenes was successfully achieved under the optimized conditions, giving dialyl [2] and [4] dendralenes in good yields.     

A new entry to the synthesis of substituted azetidines: [2+2] cycloaddition reaction of four-membered endocyclic enamides to ketenes

The first example of a [2+2] cycloaddition reaction of a four-membered endocyclic enamide (2-azetine) to dichloroketene is described and constitutes a new entry to the synthesis of substituted azetidines. Preliminary studies concerning the Baeyer-Villiger oxidation of the [2+2] cycloadduct revealed an unusual regioselectivity. The synthesis of a new azetidine-3-carboxylic acid derivative from the [2+2] cycloadduct is also presented.     

Halocyclization of 3-allylthio-5H-[1,2,4]triazino[5,6-<Emphasis Type="Italic">b</Emphasis>]indole

The synthesis of 3-allylthio-5H-[1,2,4]triazino[5,6-b]indole has been carried out by the reaction of 3-mercapto-5H-[1,2,4]triazino[5,6-b]indole with allyl bromide in the NaOH–H₂O–DMSO system and in a one-pot synthesis from isatin-β-thiosemicarbazide. Halocyclization of allylthio-5H-[1,2,4]-triazino[5,6-b]indole synthesized the 3-halomethyl-3,10-dihydro-2H-[1,3]thiazolo[3',2':2,3][1,2,4]-triazino[5,6-b]indolium halides.     

Metabolism of [2-14C]thymine and [2-14C]thymidine in germinating black gram (Phaseolus mungo) seeds

The metabolism of [2-14C]thymine and [2-14C]thymidine in the cotyledons and embryonic axes of black gram (Phaseolus mungo) seedlings was investigated. Both [2-14C]thymine and [2-14C]thymidine degraded extensively into [14C]CO2. The rate of release of [14C]CO2 from [2-14C]thymine was much greater than that from [2-14C]thymidine. Radioactivity from both precursors was also observed beta-ureidoisobutyric acid. This indicated that thymine was degraded by the reductive pathway of pyrimidine degradation. Small amounts of [2-14C]thymine and [2-14C]thymidine were salvaged for deoxyribonucleotide and DNA synthesis. The highest incorporation of [2-14C]thymine and [2-14C]thymidine into the DNA fraction was observed in 24 hour-old cotyledons where net DNA synthesis was not observed. These precursors seem to be utilised for DNA synthesis of organelles of the cotyledonary cells, probably mitochondria. In embronic axes, [2-14C]thymine is more effectively salvaged for DNA synthesis than [2-14C]thymine. The incorporation rate increased during the early phase of germination and attained its maximum at 48 h after which it decreased. No thymidine kinase activity was detected in either cotyledons or in the embryonic axes. Thymidine salvage seems to be catalysed by nucleoside phosphotransferase which is present both in the cotyledons and in the embryonic axes. This suggests that, in contrast to other pyrimidine and purine bases and nucleosides, no specific salvage system for thymine and thymidine is present in black gram seedlings.     

Synthetic studies on stevastelins. 1. Total synthesis of stevastelins B and B3

[Chemical reaction: See text] The synthesis of stevastelin B3 (2) and B (5) are described. In a first approach, epoxy cyclodepsipeptide 8 was considered as a promising candidate for the synthesis of the [15]-membered ring members of the stevastelins; however, the oxirane ring opening, required for the completion of the natural stevastelin synthesis, failed. Thus, we synthesized stevastelin B (5), carrying out the oxirane ring opening earlier in the synthesis and following a synthetic scheme capable of delivering analogues. On the other hand, a translactonization reaction of the [15]-membered ring derivative 59 led to the total synthesis of the natural [13]-membered ring component of the stevastelins family, stevastelin B3 (2).     

Carbon-rich molecules: synthesis and isolation of aryl/heteroaryl terminal bis(butadiynes) (HC[triple bond]C-C[triple bond]C-Ar-C[triple bond]C-C[triple bond]CH) and their applications in the synthesis of oligo(arylenebutadiynylene) molecular wires

The synthesis, isolation and characterisation are reported for a series of terminal aryl/heteroaryl bis(butadiynes) (HC[triple bond]C-C[triple bond]C-Ar-C[triple bond]C-C[triple bond]CH) 4a-e including the X-ray molecular structure of the 2,5-pyridylene derivative 4d; compound 4a and the mono-protected analogue [HC[triple bond]C-C[triple bond]C-Ar-C[triple bond]C-C[triple bond]C-C(OH)Me2] 5a serve as convenient precursors for the synthesis of highly-conjugated oligo(arylenebutadiynylene)s.     

Total synthesis of (-)-8-O-methyltetrangomycin (MM 47755)

A stereoselective total synthesis of the natural antibiotic (-)-8-O-methyltetrangomycin 1 is reported. The essential steps for this convergent synthesis are the transformation of a geraniol epoxide into a chiral octadiyne derivative, which was converted into a triyne. The cobalt-mediated [2+2+2] cycloaddition of the triyne led to a benz[a]anthracene system, which was oxidized with Ag(Py)(2)MnO(4) to a benz[a]anthraquinone. Deprotection with aqueous HF in acetonitrile and photooxidation afforded the desired product (-)-1. [reaction: see text]     

Synthesis of [2]- and [3]rotaxanes through Sonogashira coupling

The synthesis of new [2]- and [3]rotaxanes through Sonogashira coupling has been accomplished in the aim to built oligo(phenyleneethynylene) (OPE) encircled by crown ethers. Optimization of the Sonogashira coupling for the formation of the [2]rotaxane (capping reaction) is presented and the best method has been applied for the synthesis of the longer [3]rotaxane.     

Synthesis and applications of angular acyl-substituted azulenones: formal synthesis of (±)-acorenol and facile access to the hydroazulene core of pseudolaric acid

Azulenones with an angular acyl substituent were synthesized by the reactions of 2-aryl-2-chloroacylketenes with phenylthioacetylene or ethoxyethyne. Acyl-substituted azulenones with a methoxy group in the cycloheptatriene moiety could be rearranged to spiro[4.5] compounds. Spiro[4.5] and bicyclo[5.3.0]decane ring systems were constructed en route to a formal synthesis of (±)-acorenol and synthesis of the hydroazulene core of pseudolaric acid, respectively.     

Expeditious synthesis of N-bridged heterocycles via dipolar cycloaddition of pentafulvenes with 3-oxidopyridinium betaines

A new and highly versatile approach towards the synthesis of bicyclo[6.3.0]undecanes and bicyclo[5.3.0]decanes was accomplished. The methodology adopted involved [6+3] and [3+2] cycloaddition reactions of pentafulvenes with 3-oxidopyridinium betaines generated either by the action of a base on the pyridinium salt or thermally from pyridinium betaine dimer. These well-functionalized bicyclo[6.3.0]undecanes and bicyclo[5.3.0]decanes offer a wide range of synthetic options, which can be expected to translate into a variety of rapid and efficient synthesis of natural products.     

Rhodium-Catalyzed Enantioselective Synthesis,Structures, and Properties of Single and Double Azahelicene-Like Molecules

The enantioselective synthesis of aza[6] and [7]helicene-like molecules have been achieved by the cationic rhodium(I)/axially chiral biaryl bisphosphine complex-catalyzed intramolecular [2+2+2] cycloaddition of cyanodiynes. This protocol was successfully applied to the diastereo- and enantioselective synthesis of an S-shaped double aza[6]helicene-like molecule with a high ee value of 89 %. Although no epimerization and racemization were observed in the double carbo[6]helicene-like molecule at 80 °C, epimerization and racemization of the double aza[6]helicene-like molecule proceeded at 80 °C. This double aza[6]helicene-like molecule showed good fluorescent quantum yields and chiroptical responses under both neutral and acidic conditions.     

A novel entry to dispiropyrrolo-bicyclo[2.2.1]heptanes through sequential 1,3-dipolar and Diels-Alder cycloaddition reactions

The synthesis of novel dispiroheterocycles containing a bicyclo[2.2.1]heptane ring system through sequential [3+2] and [4+2] cycloadditions is described.     

Visible‐Light Photoredox Catalysis Enables the Biomimetic Synthesis of Nyingchinoids A,B, and D,and Rasumatranin D

The total synthesis of nyingchinoids A and B has been achieved through successive rearrangements of a 1,2‐dioxane intermediate that was assembled using a visible‐light photoredox‐catalysed aerobic [2+2+2] cycloaddition. Nyingchinoid D was synthesised with a competing [2+2] cycloaddition. Based on NMR data and biosynthetic speculation, we proposed a structure revision of the related natural product rasumatranin D, which was confirmed through total synthesis. Under photoredox conditions, we observed the conversion of a cyclobutane into a 1,2‐dioxane through retro‐[2+2] cycloaddition followed by aerobic [2+2+2] cycloaddition.     

Research on thiophenes

Thieno[2, 3-b]thiophene is prepared in a way similar to that previously described for the synthesis of thieno[3, 2-b]thiophene, the method being based on intramolecular condensation of methyl (3-formyl-2-thienylmercapto) acetate. The IR and PMR spectra of thieno[2, 3-b]-thiophene, 2-ethylthieno[2, 3-b] thiophene and 2-ethylthieno[3, 2-b]-thiophene are investigated.For Part IX see [13].     

Facile and convenient syntheses of 6,11-dihydro-5H-indeno[1,2-c]isoquinolin- 5-ones and 6,11-dihydro-5H-indolo[3,2-c]isoquinolin-5-one

[reaction: see text] The synthesis of 6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-ones from the base-promoted condensation reaction of homophthalic anhydride and 2-(bromomethyl)-benzonitrile and a convenient method for the synthesis of indolo[3,2-c]isoquinolinones are described.     

Synthesis of [5'-13C]ribonucleosides and 2'-deoxy[5'-13C]ribonucleosides

The present efficient synthesis of [5'-13C]ribonucleosides and 2'-deoxy[5'-13C]ribonucleosides is characterized by the synthesis of the D-[5-13C]ribose derivative as an intermediate via the Wittig reaction of 4-aldehydo-D-erythrose dialkyl acetals with Ph3P13CH3I-BuLi to introduce the 13C label at the 5-position of a pentose. This was followed by the highly diastereoselective osmium dihydroxylation for the preparation of 2,3-di-O-benzyl-D-[5-13C]ribose dialkyl acetal and the cyclization from D-[5-13C]ribose dialkyl acetal derivatives to the alkyl D-[5-13C]ribofuranoside derivative by the use of LiBF(4). The obtained D-[5-13C]ribose derivative was converted into [5'-13C]ribonucleosides and subsequently into the corresponding 2'-deoxynucleosides.