A novel construction of quino-fused tropone skeleton: first synthesis of 12H-benzo[4,5]cyclohepta[1,2-b]quinolin-12-one derivatives

In the present investigation, the incorporation of both quinoline moiety and tropone ring in a molecule frame work in fused form leading to a series of structurally novel and biologically intriguing quinoline/tropone hybrids 12H-benzo[4,5]cyclohepta[1,2-b]quinolin-12-one derivatives has been first achieved through a simple, and economical two-step procedure, involving the one-pot synthesis of (E)-2-(arylvinyl)quinoline-3-carboxylic acids followed by intramolecular Friedel–Crafts acylation reaction using polyphosphoric acid (PPA).     

Total synthesis of the marine pyridoacridine alkaloid sebastianine A

The synthesis of the marine alkaloid sebastianine A and of a regioisomer has been accomplished via hetero-Diels-Alder reaction of indole-4,7-dione or N-tosylindole-4,7-dione with trifluoroacetamidocinnamaldehyde dimethylhydrazone, and subsequent cyclisation in alkaline conditions.     

Synthesis of the acylphloroglucinols rhodomyrtone and rhodomyrtosone B

In a sequential three-component coupling syncarpic acid, 3-methylbutanal and an acylated phloroglucinol were combined to the hydroxy ketone 3. Acid catalysis converted 3 directly to the natural product rhodomyrtosone B (2). The other isomer, the antibiotic rhodomyrtone (1) was obtained from 3 in a sequence of acid-catalyzed cyclization, retro Friedel–Crafts reaction, and reacylation. In preliminary assays both compounds showed potent antibiotic activity.     

Structures of the Intermediate Complexes in Friedel-Crafts Acylations

Addition compounds of Lewis acids MX_n and acyl halides R? COX occur as intermediates in Friedel-Crafts acylations. IR and NMR studies on these intermediates have indicated the probable existence of structural isomers. In X-ray structural analysis, it is possible to distinguish two forms, i.e. the molecular form, in which the compounds are present as donor-acceptor complexes R? CXO→MX_n, and the ionic form, in which they can be formulated as oxocarbenium salts [R? CO]⁺[MX_n+1]^?. The compounds of the donor-acceptor type R? CXO→MX_n are characterized by the formation of a coordinate oxygen-metal bond; the transfer of electrons from the oxygen to the metal of the acceptor is always due to a weak donor-acceptor interaction. The positive charge of the aryloxocarbenium ions is partly delocalized over the aromatic nucleus. The positive charge in alkyloxocarbenium ions, on the other hand, is essentially localized on the carbon atom of the carbonyl group, as is confirmed by electron density distribution calculations.     

The synthesis of novel aliphatic bis(acenaphthelene) reactive monomers

Novel aliphatic‐bridged bis(acenaphthalene)s are synthesized and evaluated as potential precursors to high‐temperature reactive monomers. It was found that as the length of the aliphatic bridging unit increased, the thermal stability of bis(acenaphthalene) increased and melting point decreased. The use of an alternative route for the introduction of the reactive vinyl group resulted in a dramatic increase in monomer purity. The increase in monomer purity resulted in the creation of a processing window that enabled samples to be melt cast prior to polymerization, greatly improving their suitability as high‐temperature polymers. Polymerized samples were found to have high thermal stability, indicating they have potential as high temperature materials. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43:5072–5082, 2005     

Synthesis of 6- to 10-membered ring (E)-hydroxyiminohydroazaazoniabenzocycloalkenes derivative from cyclization of 2-nitromethylene-1-(ω-phenylalkyl)imidazolidine or 2-nitromethylene-1-(ω-phenylalkyl)hexahydropyrimidine in trifluoromethanesulfonic acid

In trifluoromethanesulfonic acid, 2-nitromethylene-1-(ω-phenylalkyl)imidazolidine or 2-nitromethylene-1-(ω-phenylalkyl)hexahydropyrimidine derivatives undergo an intramolecular cyclization to afford (E)-hydroxyiminohydroazaazoniabenzocycloalkenes, in their trifluoromethanesulfonate salt form. The reaction probably occurres via the formation of an electrophilic transient hydroxynitrilium ion (or O-protonated nitrile oxide). The yields are generally good, except for the higher-membered ring derivatives.     

Synthesis of a novel pyrrolo-benzoxaborole scaffold and its derivatization via Friedel–Crafts reaction catalyzed by anhydrous stannic chloride

A novel pyrrolo-benzoxaborole, 6-(pyrrol-1-yl)-1,3-dihydro-1-hydroxy-2,1-benzoxaborole, was synthesized with 27% overall yield over six steps from 2-bromo-1-methyl-4-nitrobenzene as starting material. Its derivatization was achieved via Friedel–Crafts reaction catalyzed by anhydrous stannic chloride with various acyl chlorides giving 3-acyl-1-phenylpyrroles as the main products.     

A Three‐Minute Synthesis and Purification of Ibuprofen: Pushing the Limits of Continuous‐Flow Processing

In a total residence time of three minutes, ibuprofen was assembled from its elementary building blocks with an average yield of above 90 % for each step. A scale‐up of this five‐stage process (3 bond‐forming steps, one work‐up, and one in‐line liquid–liquid separation) provided ibuprofen at a rate of 8.09 g h^?1 (equivalent to 70.8 kg y^?1) using a system with an overall footprint of half the size of a standard laboratory fume hood. Aside from the high throughput, several other aspects of this synthesis expand the capabilities of continuous‐flow processing, including a Friedel–Crafts acylation run under neat conditions and promoted by AlCl₃, an exothermic in‐line quench of high concentrations of precipitation‐prone AlCl₃, liquid–liquid separations run at or above 200 psi to provide solvent‐free product, and the use of highly aggressive oxidants, such as iodine monochloride. The use of simple, inexpensive, and readily available reagents thus affords a practical synthesis of this important generic pharmaceutical.     

Enantioselective synthesis of (−)-(1R,2R)-1,2-dihydrochrysene-1,2-diol

A general chiral building block containing the 1R,2R-trans-diol moiety was constructed utilizing the stereoselective Shi-epoxidation reaction on a tetralone scaffold assembled by a Negishi cross-coupling on N,N-diethylbenzamide. Further elaboration of this chiral building block into polycyclic aromatic compounds was demonstrated with the total synthesis of the precursor for the most carcinogenic metabolite of chrysene, (−)-(1R,2R)-1,2-dihydrochrysene-1,2-diol in 87% ee.     

Direct electron transfer of glucose oxidase and dual hydrogen peroxide and glucose detection based on water-dispersible carbon nanotubes derivative

A water-dispersible multi-walled carbon nanotubes (MWCNTs) derivative, MWCNTs-1-one-dihydroxypyridine (MWCNTs-Py) was synthesis via Friedel–Crafts chemical acylation. Raman spectra demonstrated the conjugated level of MWCNTs-Py was retained after this chemical modification. MWCNTs-Py showed dual hydrogen peroxide (H₂O₂) and glucose detections without mutual interference by adjusting pH value. It was sensitive to H₂O₂ in acidic solution and displayed the high performances of sensitivity, linear range, response time and stability; meanwhile it did not respond to H₂O₂ in neutral solution. In addition, this positively charged MWCNTs-Py could adsorb glucose oxidase (GOD) by electrostatic attraction. MWCNTs-Py-GOD/GC electrode showed the direct electron transfer (DET) of GOD with a pair of well-defined redox peaks, attesting the bioactivity of GOD was retained due to the non-destroyed immobilization. The high surface coverage of active GOD (3.5 × 10⁻⁹ mol cm⁻²) resulted in exhibiting a good electrocatalytic activity toward glucose. This glucose sensor showed high sensitivity (68.1 μA mM⁻¹ cm⁻²) in a linear range from 3 μM to 7 mM in neutral buffer solution. The proposed sensor could distinguish H₂O₂ and glucose, thus owning high selectivity and reliability.     

A ring closing metathesis approach to the indole alkaloid mitralactonine

An efficient utilisation of RCM leading to a convenient synthesis of a pentacyclic indole alkaloid is described.     

Heterocyclic analogs of pleiadiene. 70. Synthesis of 6-hydroxy-1,3-diazapyrenes

The regioselectivity of the reactions of perimidine with cinnamic acids in polyphosphoric acid (PPA) depends on the P₂O₅ content. Procedures were developed for the synthesis of 4(9)- and 6(7)-cinnamoylperimidines. Cyclization of the latter under the action of an excess of AlBr₃ was accompanied by dearylation to form 6-hydroxy-1,3-diazapyrene.     

A new synthetic approach to the C ring of known as well as novel bryostatin analogues

[reaction: see text] A new approach to the synthesis of the C ring subunit of known and potential bryostatin analogues is described. The convergent approach, illustrated above, requires fewer steps and offers greater flexibility in rapidly accessing diverse C ring analogues.     

Stereoselective Total Synthesis of Xestodecalactone C

A simple and highly efficient stereoselective total synthesis of xestodecalactone C ( IIb ), a polyketide natural product, was achieved (Scheme 2). The synthesis involved Keck's asymmetric allylation, a iodine‐induced electrophilic cyclization, and an intramolecular Friedel–Crafts acylation as key steps.     

A novel approach to carbocyclic analogues of nucleosides

(±)-1-[(1α,3α,4α)-3-Hydroxy-4-hydroxymethlcyclopentyl]- (1H,3H-pyrimidin-2,4-dione (6) was synthesized starting from endo-5-norbornen-2-yl acetate via the urea derivative 5 in 32% overall yield.     

Synthesis of a novel naphthalene-based poly(arylene ether-ketone) by polycondensation of 1,5-bis(4-fluorobenzoyl)-2,6-dimethylnaphthalene with bisphenol a

Synthesis of 1,5-bis(4-fluorobenzoyl)-2,6-dimethylnaphthalene ( 1 ), polycondensation of 1 with Bisphenol A, and properties of the obtained polymer were studied. Friedel–Crafts acylation of 2,6-dimethylnaphthalene with 4-fluorobenzoyl chloride in nitrobenzene selectivity afforded 1 in 82% yield. X-ray single crystal structural analysis of 1 confirmed that the dibenzoylation proceeded regioselectively and two methyl groups sterically inhibited the coplanarity of the two aromatic planes. The polycondensation of 1 with Bisphenol A in toluene/N-methyl-2-pyrrolidone (NMP) mixed solvent in the presence of excess potassium carbonate as a condensation reagent was carried out at 180°C for 4 h to quantitatively afford the corresponding poly(arylene ether-ketone) (PEK) 3 with high molecular weight (M?_n～30,000) as a slightly yellow powder. As the reaction time was prolonged, both M?_n and MWD of 3 increased and the solubility of 3 in chloroform clearly decreased. By GPC-LALLS, M?_n of 3 obtained by the polycondensation for 16 h, was 85,000. The PEK 3 with high molecular weight was produced in a quantitative yield in a variety of solvents such as sulfolane. Water formed during the polycondensation hardly affected the yield and molecular weight of 3 , although a small molecular weight decrease took place. To evaluate the special effect of the methyl groups of 3 , polycondensation of 2,6-bis(4-fluorobenzoyl)naphthalene 2 with bisphenol A was carried out for comparison and the corresponding PEK 4 was quantitatively obtained. Whereas 3 was soluble in ordinary organic solvents such as tet-rahydrofuran (THF), chloroform, and NMP at room temperature, 4 was insoluble in most solvents except for strong acids such as conc. sulfonic acid. The polymer 3 showed high glass transition temperature (238°C) and 5% weight loss temperature (457°C). Casting of the polymer from THF solution gave a transparent, tough, flexible, and amorphous film. © 1995 John Wiley & Sons, Inc.     

A new synthetic approach to the C-D ring portion of streptonigrin analogues

Development of an efficient synthesis of the C-D ring portion of streptonigrin is a key operation in the synthesis of this antibiotic and its analogues. A new method for the synthesis of 3-cyano-5,6-dimethyl-4-(3,4,5-trimethoxyphenyl)-2-pyridone ( 14 ), a compound having the requisite functionality for conversion into a streptonigrin analogue, has been established. It involves treatment of 3,4,5-trimethoxybenzonitrile with ethylmagnesium bromide and malononitrile to give propylenemalononitrile derivative 7 , which is condensed with trimethyl orthoacetate to give a mixture of 9 and pyridine derivative 12 . Demethylation of 12 then affords 14 . The overall yield for this route was 50%, allowing for conversion of 9 to 12 .     

The synthesis of the central tricyclic core of the isatisine A: harmonious orchestration of [metal]-catalyzed reactions in a sequence

Two sequential metal-catalyzed transformations, involving [In]-catalyzed Friedel–Crafts type addition of spiroaminol carbon to indole C3 followed by [Rh]-catalyzed dehydrogenative cyclization of the resulting γ-amino alcohol culminated in the construction of the central tricyclic core isatisine A. The overall strategy employed three easily available starting compounds and delivered the complex tricyclic core in four steps—with all four steps being catalytic in nature.     

Synthesis of marine sponge alkaloid hachijodine B and a comment on the structure of ikimine B and on the absolute configuration of niphatesine D

The syntheses of the proposed structures of hachijodine B 1, ikimine B 2 and niphatesine D 3 from S-citronellol are described. Our results suggest that the gross structures of hachijodine B and niphatesine D are correct, but that ikimine B was incorrectly assigned. We have also established that the previous absolute stereochemical assignment for niphatesine D is unreliable.     

Enzymatic Benzofuranoindoline Formation in the Biosynthesis of the Strained Bridgehead Bicyclic Dipeptide (+)-Azonazine A

We uncovered and reconstituted a concise biosynthetic pathway of the strained dipeptide (+)-azonazine A from marine-derived Aspergillus insulicola. Formation of the hexacyclic benzofuranoindoline ring system from cyclo-(l -Trp-N-methyl-l -Tyr) is catalyzed by a P450 enzyme through an oxidative cyclization. Supplementing the producing strain with various indole-substituted tryptophan derivatives resulted in the generation of a series of azonazine A analogs.