A new synthesis of (−)-thioambrox and its 8-epimer

This new and straightforward synthesis of (−)-thioambrox 2, a sulphur compound whose odour resembles ambergris, starts from sclareolide 4. The stereoselectivity of the final cyclization is independent of the catalyst selected, and compound 2 is always favoured over (+)-iso-thioambrox 3. With hydrochloric acid as catalyst, the cyclization is unexpectedly stereospecific to give 2 in high yield at room temperature.     

10b-Substituted hexahydropyrrolo-isoquinolines: studies on diastereoselective formation of a quaternary carbon stereocenter via N-acyliminium ion cyclization

The stereoselective synthesis of hexahydro-pyrroloisoquinolines with a quaternary carbon stereocenter is described. The presented methodology employs the addition of a Grignard reagent to the carbonyl group of imide 1, derived from l-tartaric acid, followed by acetylation and BF₃·Et₂O induced cyclization. The acetylation-cyclization sequence can be run either as a one-pot process, or stepwise in a selected solvents. The crucial step, an acid-catalyzed carbon-carbon bond-forming reaction via an N-acyliminium ion offers high stereoselectivity, which has been shown to be strongly dependent on the size of the R¹ substituents and the reaction conditions, that is, choice of solvent, amount of a Lewis acid, temperature, and concentration of the substrate. Based on the results observed, participation of solvent in the cyclization, via an N-acyliminium cation is proposed.     

Novel synthesis of benzo[b]carbazoles

A new method was adopted for the synthesis of benzo[b]carbazoles by Claisen condensation followed by Fischer indole cyclization. Newly synthesized benzo[b]carbazoles were treated with ethanol amine in the presence of polyphosphoric acid which leads to the formation of pyrazino carbazoles. All the synthesized compounds were characterized by all spectral means.     

Stereoselective total synthesis of 4-((3S,5R)-3,5-dihydroxynonadecyl)phenol

A stereoselective total synthesis of 4-((3S,5R)-3,5-dihydroxynonadecyl)phenol has been accomplished in two different synthetic approaches. In the first approach, Prins cyclization has been successfully utilized to produce the anti-1,3-diol unit, which was further converted into a required syn-1,3-diol through Mitsunobu reaction. The side chain was constructed through cross metathesis and hydrogenation sequence. In the second approach, the chiral syn-1,3-diol was prepared by a sequence of reactions such as alkylation of 1,3-dithane with (R)-epichlorohydrin, ring opening of the epoxide with vinylmagnesium bromide, and 1,3-syn-reduction of the β-hydroxyketone with NaBH₄ in the presence of diethylmethoxyborane.     

Solid-phase synthesis of fused [2,1-b]quinazolinone alkaloids

Solid-phase synthesis of fused [2,1-b]quinazolinone alkaloids has been developed for the preparation of vasicinone and deoxyvasicinone by two approaches. The derivative of polymer-supported p-nitrophenyl carbonate was attached to anthranilic acid and then coupled with various bromo-lactams. This resin-linked bromo intermediate upon acetylation, hydrolysis and resin cleavage gave the cyclized [2,1-b]quinazolinones (vasicinone). Alternatively, resin-linked azido-benzoic acids were coupled with bromo-substituted lactams followed by cyclization in an aza-Wittig reductive cyclization process giving the bromo-substituted quinazolinone intermediates, with subsequent acetylation, hydrolysis and resin cleavage affording the fused [2,1-b]quinazolinones.     

Aryl radical cyclizations of N-(2-halobenzoyl)-cyclic ketene-N,S-acetals

2-Ethylthiazolines react with 2-halobenzoyl chlorides to form N-(2-halobenzoyl)-cyclic ketene-N,S-acetals, which undergo stereo-controlled radical cyclizations to afford (R,S,S)-3-alkyl-10-methyl-2,3,10,10a-tetrahydrothiazolo[3,2-b]isoquinolin-5-one and (R,R,S)-3-alkyl-10-methyl-2,3,10,10a-tetrahydrothiazolo[3,2-b]isoquinolin-5-one.     

Diastereoselective synthesis of 10b-substituted hexahydropyrroloisoquinolines from l-tartaric acid. Creation of a quaternary carbon stereocentre via N-acyliminium ion cyclization

A simple, three-step synthesis of 10b-substituted-hexahydropyrroloisoquinolines 12-17 starting from an L-tartaric acid derived imide is described. The methodology presented employs the addition of a Grignard reagent to the imide carbonyl group, followed by a one-pot acetylation-cyclization sequence. The crucial step, an acid-catalyzed carbon-carbon bond forming reaction via an N-acyliminium ion offers moderate to high stereoselectivity, which has been shown to be strongly dependent on the size of the R-substituent. The mixtures of pyrroloisoquinolines obtained can be separated as enantiomerically pure 2-silyloxy-derivatives.     

Practical enantioselective synthesis of (3S, 4R)-3-hydroxypiperidine-4-carboxylic acid

A practical enantioselective synthesis of (3S, 4R)-3-hydroxypiperidine-4-carboxylic acid was accomplished via an unconventional Evans anti-aldol reaction followed by a one-pot azide reduction/reductive cyclization.     

Stereoselective synthesis of (−)-tetrahydrolipstatin via a radical cyclization based strategy

An efficient and flexible approach for the total synthesis of (−)-tetrahydrolipstatin is described. The main features of the synthetic strategy are a stereocontrolled radical cyclization and the successful utilization of commercially available S-malic acid.     

Me3SiCl-promoted intramolecular cyclization of aromatic compounds tethered with N,O-acetals leading to the facile preparation of 1,4-benzodiazepine skeletons

The Me₃SiCl-promoted intramolecular aminomethylation of a novel type of N,O-acetals, which were prepared via a facile three-step synthesis from N-alkylaniline derivatives and N-alkyl-2-oxazolidinones that leads to the production of pharmaceutically useful 1,4-benzodiazepine skeletons with a variety of functional groups is described. This method was successfully applied to the facile preparation of both tricyclic benzodiazepine derivatives and a 1,4-benzoxazepine derivative via 7-exo-trig cyclization.     

Mechanism of an unusual decarboxylative cyclization

The mechanism of an unusual decarboxylative cyclization from 5-methoxy-1-(2-carboxyphenyl)-1,4-dihydro-4-oxopyridine-2-carboxylic acid (diacid) to 3-methoxypyrido[1,2-a]indole-2,10-dione (ketone) has been investigated. ¹³C-labeling has demonstrated that the carbonyl carbon of the ketone arises exclusively from the anthranilic acid carboxyl of the diacid. A zwitterionic mechanism has been proposed.     

Regioselective synthesis of substituted 1-indanols, 2,3-dihydrobenzofurans and 2,3-dihydroindoles by electrochemical radical cyclization using an arene mediator

Electrochemical reduction of haloarenes carrying 2-(1-hydroxybut-3-enyl), 2-allyloxy or N-allyl-N-methylamino group in the presence of phenanthrene as a mediator generated the corresponding aryl radicals and gave the corresponding 5-exo cyclization products in good yields. Higher regio- and stereoselectivities than those of usual radical cyclization using AIBN-Bu₃SnH were achieved.     

Synthesis, characterization and intercalation property of layered zirconium benzylamino-N,N-dimethylphosphonate phosphate materials

Layered zirconium benzylamino-N,N-dimethylphosphonate phosphate (ZBMPA) was prepared by the reaction of zirconyl chloride with benzylamino-N,N-dimethylphosphonic acid (H₂BMPA) and phosphoric acid in the presence of hydrofluoric acid. The intercalation of n-alkylamines (n-butylamine, n-heptylamine and n-decylamine) into ZBMPA was primarily investigated at room temperature. These materials were characterized by elemental analysis, ICP, XRD, SEM, FT-IR, Raman spectra, TG and DSC. The composition of ZBMPA is Zr(HPO₄)(C₆H₅CH₂N(CH₂PO₃)₂)_0.5 · 2.0H₂O. The interlayer distance of ZBMPA, n-butylamine, n-heptylamine and n-decylamine intercalation compounds is 2.03, 2.58, 2.52 and 3.17 nm, respectively. ZBMPA and the n-alkylamine intercalation compounds are different in the morphology and vibration spectra. Thermogravimetries of all materials obtained reveal three step mass losses at temperatures of up to 1000 °C. These results indicate that n-alkylamines are intercalated into the galleries of host ZBMPA.     

Intramolecular α-acylamino radical cyclizations with acylsilanes in the preparation of polyhydroxylated alkaloids: (+)-lentiginosine, (+)-1,8a-di-epi-lentiginosine, and (+)-1,2-di-epi-swainsonine

Acylsilanes with latent α-acylamino radical functionality were prepared from different chiral templates. Radical cyclizations of these acylsilanes efficiently constructed polyhydroxylated indolizidine derivatives with excellent stereoselectivity at the bridgehead position. These cyclization products were converted to (+)-lentiginosine, (+)-1,8a-di-epi-lentiginosine, and (+)-1,2-di-epi-swainsonine.     

Microbial reduction of coumarin, psoralen, and xanthyletin by Glomerella cingulata

Microbial transformation of coumarin, psoralen, and xanthyletin was performed with the fungus Glomerella cingulata. The main reaction pathways involved reduction at α,β-unsaturated δ-lactone ring on coumarin analogue. Coumarin was metabolized by G. cingulata to give the corresponding reduced acid, hydrocoumaric acid. In the biotransformation of psoralen, two reduced metabolites, 6,7-furano-hydrocoumaric acid, and 6,7-furano-o-hydrocoumaryl alcohol were isolated from the incubation of psoralen. Xanthyletin was converted to reduced products 9,9-dimethyl-6,7-pyrano-hydrocoumaric acid and 9,9-dimethyl-6,7-pyrano-o-hydrocoumaryl alcohol by G. cingulata. The structures of the new compounds were characterized using spectroscopic techniques. In addition, all of compounds including methyl ester derivatives of the metabolites were tested for the β-secretase (BACE1) inhibitory activity in vitro. 6,7-Furano-hydrocoumaric acid methyl ester was shown to possess BACE1 inhibitory activity, and an IC₅₀ value was 0.84 ± 0.06 mM.     

Catalytic photocarboxylation of 1,1-diphenylethylene with N,N,N′,N′-tetramethylbenzidine and carbon dioxide

Photocarboxylation of 1,1-diphenylethylene with N,N,N′,N′-tetramethylbenzidine (TMB) in MeCN under bubbling of CO₂ proceeded with high catalytic efficiency, giving 3,3-diphenylacrylic acid (DPA) and 3-hydroxy-3,3-diphenylpropionic acid (20). The turnover number (TON=(DPA+20)/TMB) reached 17. Similarly, 1-phenyl-1-cyclohexene yielded cis-2-acetamido-2-phenylcyclohexanecarboxylic acid with TON 5.9. As compared with related N,N-dimethylaniline derivatives, TMB is more resistant to photodecomposition, has the much larger absorbance in the S₀→S₁ transition, and has the lower quenching efficiency by CO₂. Probably these factors are partly responsible for the high TON observed for TMB.     

Laetiporic acid, a new polyene pigment from the wood-rotting basidiomycete Laetiporus sulphureus (Polyporales, Fungi)

A new pigment, laetiporic acid, has been isolated from fruit-bodies of the wood-rotting fungus Laetiporus sulphureus (sulfur shelf). Structure elucidation by application of extensive 2D NMR techniques permitted its identification as a polyene of non-isoprenoid origin. Laetiporic acid, which represents the main pigment in L. sulphureus basidiocarps, bears an unprecedented decaene skeleton as part of its chromophore and, interestingly, contains double bonds with a stable cis configuration.     

Photochemical radical cyclization of γ,δ-unsaturated ketone oximes to 3,4-dihydro-2H-pyrroles

3,4-Dihydro-2H-pyrroles are synthesized from γ, δ-unsaturated oximes by photochemical radical cyclization with 1,5-dimethoxynaphthalene (DMN) as the sensitizer. The cyclization of alkyl ketone O-acetyloximes proceeds via photosensitized electron transfer in the presence of acetic acid, while conjugated oximes of aryl and α,β-unsaturated ketones are cyclized via energy transfer.     

Synthetic entry to the ABCD ring fragment of gymnocin-A, a cytotoxic marine polyether

Synthetic entry to the ABCD ring fragment of gymnocin-A, a cytotoxic marine polyether, has been achieved based on the B-alkyl Suzuki-Miyaura coupling-based strategy and radical cyclization for the construction of the tetrahydrofuran ring A.     

VioE, a prodeoxyviolacein synthase involved in violacein biosynthesis, is responsible for intramolecular indole rearrangement

Indole-3-pyruvic acid is transformed to prodeoxyviolacein by the novel enzyme VioE, which is involved in the violacein biosynthetic pathway in Chromobacterium violaceum ATCC12472. VioE catalyzes the decarboxylation and indole-ring rearrangement of a nascent compound that is produced from indole-3-pyruvic acid and by the action of chromopyrrolic acid synthase (VioB or StaD), and ultimately the reaction yields prodeoxyviolacein.