Synthesis and properties of a new member of the calixnaphthalene family: a C(2)-symmetrical endo-calix[4]naphthalene

The synthesis of a new endo-calix[4]naphthalene is described. The reaction sequence involves the cyclocondensation of a key bisnaphthylmethane intermediate (8) with formaldehyde. This key intermediate (8) is formed using a modified Suzuki-Miyaura Pd-catalyzed cross-coupling reaction between bromomethylnaphthyl (6) and naphthylboronic acid (7), both of which can be derived from 2-hydroxynaphthoic acid.     

Pd(II)-Catalyzed Regioselective 2-Alkylation of Indoles via a Norbornene-Mediated C-H Activation: Mechanism and Applications

A palladium-catalyzed direct 2-alkylation reaction of free N-H indoles was developed based on a norbornene-mediated regioselective cascade C-H activation. The detailed reaction mechanism was investigated by NMR spectroscopic analyses, characterization of the key intermediate, deuterium labeling experiments, and kinetic studies. The results indicate that a catalytic cycle operates, in which an N-norbornene type palladacycle is formed as the key intermediate. Oxidative addition of alkyl bromide to the Pd(II) center in this intermediate is the rate-determining step of the reaction. The synthetic utility of this indole 2-alkylation method was demonstrated by its application in natural product total synthesis. A new and general strategy to synthesize Aspidosperma alkaloids was established employing the indole 2-alkylation reaction as the key step, and two structurally different Aspidosperma alkaloids, aspidospermidine and goniomitine, were synthesized in concise routes.     

Phototriggered Release of a Leaving Group in Ketoprofen Derivatives via a Benzylic Carbanion Pathway,But not via a Biradical Pathway

2‐Acetoxymethyl‐2‐(3‐benzoylphenyl)propionic acid (KP‐OAc) was used as a model to elucidate the solvent‐mediated photochemistry mechanism of Ketoprofen (KP). In solutions with a low concentration of water, KP‐OAc exhibits a benzophenone‐like photochemistry, reacting with water molecules through some reaction to form a ketyl radical intermediate. In neutral solutions with a high concentration of water or acidic solutions, KP‐OAc undergoes a photodecarboxylation reaction with the assistance of water molecules or with the catalysis of perchloric acid to directly generate a biradical intermediate that cannot induce the phototrigger reaction to release the AcO^? group. Therefore, the lifetime of the biradical intermediate of KP‐OAc is almost same as that of the biradical intermediate formed from KP in the same kinds of solutions. However, the photodecarboxylation of KP‐OAc in phosphate buffer solution directly produces the benzylic carbanion intermediate, which can induce the phototrigger reaction to release the AcO^? group. Therefore, the lifetime of the biradical intermediate of KP‐OAc is significantly shorter than the lifetime of the biradical intermediate of KP in phosphate buffer solution. Interestingly, the investigation of the photochemistry of KP‐OAc not only verifies the solvent‐mediated photochemistry mechanism of KP but also provides some new insight into the potential of using this kind of platform for phototrigger applications. The biradical intermediate is not the key species leading to the phototrigger reaction but the benzylic carbanion species is the key reactive intermediate that can mediate the phototrigger reaction of KP‐OAc. Therefore, a change in the pH of the solutions can be utilized to switch on and switch off the photorelease reactions of KP derivative phototrigger compounds.     

Stereoselective synthesis of fluoro-homoneplanocin A as a potential antiviral agent

Fluoro-homoneplanocin A (4) was synthesized from d-ribose, via the enyne ring-closing metathesis of 9, the stereoselective opening of epoxide 23a with fluoride, and a simultaneous oxidation-elimination reaction. The key intermediate 8 is expected to serve as a versatile intermediate for the synthesis of carbanucleosides.     

Copper‐Catalyzed Reaction of Trifluoromethylketones with Aldehydes via a Copper Difluoroenolate

A copper‐catalyzed reaction of easily accessible α,α,α‐trifluoromethylketones with various aldehydes affords difluoro‐methylene compounds in the presence of diboron and NaOtBu. The key process of the reaction is the formation of a copper difluoroenolate by 1,2‐addition of a borylcopper intermediate to α,α,α‐trifluoromethylketones and subsequent β‐fluoride elimination. Mechanistic studies including the isolation and characterization of a possible anionic copper alkoxide intermediate are also described.     

Chemoenzymatic synthesis of novel adenosine carbanucleoside analogues containing a locked 3′-methyl-2′,3′-β-oxirane-fused system

Starting from a readily available enantiopure building block, a straightforward enantioselective approach to 3′-methyl-2′,3′-β-oxirane-fused carbanucleosides bearing adenosine analogues is detailed. The key steps in the syntheses involved a lipase-catalyzed regioselective monoacylation of a diol to obtain the key intermediate and direct coupling of this key intermediate with diversely substituted purine nucleobases under Mitsunobu reaction conditions providing only the N⁹ target molecules.     

Total synthesis of (-)-kainic acid via intramolecular Michael addition: a second-generation route

A total synthesis of (-)-kainic acid starting from the commercially available 2-azetidinone is described. The key delta-lactone intermediate was concisely prepared from the commercially available azetidinone through the Reformatsky-type reaction and an introduction of a glycine moiety. The construction of the functionalized pyrrolidine ring was executed by a one-pot sequential elimination-Michael addition protocol of a beta-amino-delta-lactone intermediate with high diastereoselectivity.     

Efficient Synthesis of Beraprost Sodium

An efficient and straightforward synthesis of beraprost sodium was developed with dicyclopentadiene as a starting material, a one-pot reaction product 5 as key intermediate and the Prins reaction and the Horner-Wads- worth-Emmons reaction as key steps. The structures of the key intermediate and the target compound were confirmed by ¹H NMR, ¹³C NMR and MS. The purity of beraprost sodium identified by high performance liquid chromatography(HPLC) was identical to that of Japanese Pharmacopoeia(16^th). This development will be used for the industrial synthesis of beraprost sodium.     

A new synthesis of d1-coriolin A. Application of a new SN2 reaction at a neopentylic position

Dicyclopentadiene has been stereoselectively converted to a key tricyclic intermediate for the total synthesis of coriolin, through a route which involves a new S_N2 reaction at a neopentylic position.     

Stereoselective total synthesis of (−)-zeylenol,a key intermediate for the synthesis of (+)-pipoxide, (−)-uvarigranol G and (−)-tonkinenin A

Total synthesis of (?)-zeylenol, a key intermediate for the synthesis of (+)-pipoxide, (?)-uvarigranol G and (?)-tonkinenin A was achieved from commercially available starting material d-mannose. The key steps are mixed aldol condensation, Grignard reaction, ring closing metathesis and regioselective benzoylation.     

Studies toward a marine toxin immunogen: enantioselective synthesis of the spirocyclic imine of (-)-gymnodimine

[reaction: see text] An enantioselective Diels-Alder reaction catalyzed by an Evans' copper-bis(oxazoline) complex was utilized to construct a highly functionalized spirolactam, a key intermediate in our projected total synthesis of the marine toxin, gymnodimine. Additional transformations, including a mild N-tosyl group deprotection, afforded a keto spirocyclic imine moiety, the proposed pharmacophore of gymnodimine. Thus, the prepared ketone is a potentially useful intermediate for conjugation to provide an immunogen for eventual monitoring of gymnodimine and congeners.     

Reaction of N-monosubstituted hydrazones with nitroolefins: a novel regioselective pyrazole synthesis

A novel regioselective synthesis of substituted pyrazoles from N-monosubstituted hydrazones and nitroolefins is described. The reaction is performed in a one-pot manner and the yields range from moderate to excellent. A key nitropyrazolidine intermediate is characterized and a plausible mechanism is proposed.     

Total Synthesis of (−)‐Nakadomarin A

A highly efficient 12‐step synthesis of the marine alkaloid (?)‐nakadomarin A has been accomplished. The key advanced intermediate, a tetracyclic ketone derivative, was constructed in just seven steps using a sequence that includes an asymmetric Pauson–Khand reaction, an Overman rearrangement reaction, a ring‐closing metathesis reaction, and an amination reaction. Late introduction of the furan ring during the synthesis of (?)‐nakadomarin A means that the key tetracyclic ketone derivative has the potential to serve as an advanced intermediate for the synthesis of related marine alkaloids.     

Diastereoselective formal synthesis of a monoterpene alkaloid, (-)-incarvilline

Diastereoselective formal synthesis of a monoterpene alkaloid, (-)-incarvilline, the key intermediate for the synthesis of (-)-incarvillateine, was achieved by using an intramolecular Pauson-Khand reaction of (S)-N-[(E)-2-butenyl]-N-(3-butynyl-2-methoxymethoxy)-p-toluenesulfonamide as a key step.     

Pulsed‐EPR Evidence of a Manganese(II) Hydroxycarbonyl Intermediate in the Electrocatalytic Reduction of Carbon Dioxide by a Manganese Bipyridyl Derivative

A key intermediate in the electroconversion of carbon dioxide to carbon monoxide, catalyzed by a manganese tris(carbonyl) complex, is characterized. Different catalytic pathways and their potential reaction mechanisms are investigated using a large range of experimental and computational techniques. Sophisticated spectroscopic methods including UV/Vis absorption and pulsed‐EPR techniques (2P‐ESEEM and HYSCORE) were combined together with DFT calculations to successfully identify a key intermediate in the catalytic cycle of CO₂ reduction. The results directly show the formation of a metal–carboxylic acid–CO₂ adduct after oxidative addition of CO₂ and H⁺ to a Mn⁰ carbonyl dimer, an unexpected intermediate.     

A convenient synthesis of pyridazine-3,4-dicarboxylic acid by a hetero diels-alder reaction

A convenient route to prepare unsubstituted pyridazine-3,4-dicarboxylic acid on a preparative scale is described. The synthesis involves a hetero Diels-Alder reaction between a new 1,2-diaza-1,3-diene and ethyl vinyl ether and oxidation of the intermediate 1,4,5,6-tetrahydropyridazine as the key step.     

Asymmetric total synthesis of (-)-agelastatin a using sulfinimine (N-sulfinyl imine) derived methodologies

The asymmetric synthesis of the cytotoxic marine metabolite (-)-agelastatin A (1) has been achieved from the C-ring intermediate 4,5-diamino cyclopenten-2-enone (-)-2. This key intermediate was efficiently prepared from the sulfinimine-derived alpha,beta-diamino ester 4 using ring-closing metathesis. [reaction: see text]     

An enantioconvergent route to (-)-shikimic acid via a palladium-mediated elimination reaction

[reaction--see text] (-)-Shikimic acid, the key intermediate in the shikimate pathway in plants and microorganisms, has been synthesized in an enantioconvergent manner from both enantiomeric starting materials by employing a palladium-mediated elimination reaction as the key step.     

Enantiospecific total synthesis of both enantiomers of laurene by a chemical diastereoselection/lipase-catalyzed kinetic resolution sequence

A short and efficient enantiospecific total synthesis of natural (+)-laurene and its enantiomer is described. The methodology was developed by employing a stereoselective H-ene reaction of an isocyclic allyltrimethylsilane with paraformaldehyde, followed by a lipase-mediated kinetic resolution of the racemic key intermediate.     

一叶秋碱全合成的研究-中间体α-羟酮的合成

α-羟酮是中枢神经药物叶 碱 合中的重要中间体。本文以不同路线合成了α羟酮, 并通过与天然降解物进行光谱对照确定了结构。