Synthesis of 2,3‐Dihydroxy‐1‐Epilupinine

The 1,3‐dipolar cycloaddition of unsaturated D‐threo‐hexaldonolactone 3 and a six‐membered cyclic nitrone 11 led to a single adduct 15, which could be transformed into (1S, 2S, 3S, 9aS)‐2,3‐dihydroxy‐1‐hydroxymethyl‐quinolizidine 28 related to epilupinine via a reaction sequence involving rearrangement of the six‐membered lactone ring into a five‐membered one, removal of the terminal carbon atom from the sugar chain, cleavage of the N‐O bond, and the intramolecular alkylation of the nitrogen atom.      

Synthesis of (−)‐Isofagomine

Abstract

1,3‐Dipolar cycloaddition of N‐benzyl nitrone 2 to D‐threo δ‐lactone 15 proceeded with excellent stereoselectivity to provide only one adduct 16. Cycloadduct 16 was subsequently subjected to a sequence of reactions involving rearrangement to γ‐lactone, glycolic cleavage/reduction, protection of the terminal hydroxymethyl group, reduction of the lactone, desilylation/mesylation, and hydrogenolysis of the N‐O bond providing (?)‐isofagomine and its N‐substituted derivatives. The biologic activity of N‐substituted (?)‐isofagomines toward commercially available α‐ and β‐glucosidases, α‐D‐mannosidase, α‐L‐fucosidase, β‐D‐glucuronidase, and β‐D‐galactosidase was tested.     

Synthesis of Substituted 2‐Amino‐cyclobutanones

A series of weakly nucleophilic nitrogen derivatives including carbamates, amides, sulfonamides, and anilines were reacted with 1,2‐bis(trimethylsilyloxy)cyclobutene under acidic conditions to afford various substituted 2‐aminocyclobutanone derivatives 3a–i in modest to excellent yields.     

Simple Synthesis of 7‐Formyl‐indole

A simple route to 7‐formyl‐indole (5) is described in which appropriately functionalized o‐nitrotoluenes (1) are converted to 7‐hydroxymethyl‐indole (4) using the Batcho–Leimgruber process. Condensation of 3‐methyl‐2‐nitrobenzyl alcohol (1a) with N,N‐dimethylformamide dimethyl acetal yields the enamine 2a, which upon catalytic hydrogenation affords 4 in 22% yield. When the hydroxyl function in 1 is protected with pivaloyl or tetrahydropyranyl group, the yields of 4 are increased to 39% and 48%, respectively. Finally, 4 is oxidized with pyridinium chlorochromate (PCC) to afford 5 in 86% yield.     

Asymmetric Synthesis of (+)‐epi‐Cytoxazone

The asymmetric synthesis of (+)‐epi‐cytoxazone, a stereoisomer of potent cytokine modulator cytoxazone, starting from anisaldehyde in six steps, is described. The required configuration was established via Sharpless kinetic resolution followed by the Mitsunobu reaction.     

Synthesis of 1,1‐Dimethyl‐4‐indanol Derivatives

The synthesis of 1,1‐dimethyl‐4‐indanols (3a,b) has been achieved by intramolecular Friedel–Crafts cyclization of 2‐(3‐methyl‐2‐butenyl)phenols (5a,b) or 1‐methoxy‐2‐(3‐methyl‐2‐butenyl)benzenes (6a,b) followed by demethylation, respectively.It was found that the solvent was critical for the formation of different products in the intramolecular Friedel–Crafts reactions of 6. The unexpected product 4‐methoxy‐1,1,6,6‐tetramethyl‐as‐hydrindacene (11) was obtained from the Friedel–Crafts reactions of 6a, and its structure was confirmed by X‐ray diffraction analysis. The key intermediates 5a,b were prepared by ortho‐alkenylation of phenols with 1‐bromo‐3‐methyl‐2‐butene, and the reaction temperature exerted an obvious impact on the yield of 2‐(3‐methyl‐2‐butenyl)phenol (5a).     

Synthesis of L‐6‐Chloropyrroloindoline of Chloptosin Cyclohexapeptide

Abstract

Chloptosin is an apoptosis‐inducing dimeric cyclohexapeptide. Enantioselective synthesis of L‐6‐chloropyrroloindoline, as the key chiral synthon of the cyclohexapeptide of chloptosin, was successfully achieved starting from 3‐chloroaniline by utilizing Fischer indole/Schöllkopf protocol and oxidative cyclization of resulting L‐6‐chlorotryptophan.     

Synthesis of cis‐3‐methyl‐4‐aminopiperidine Derivatives

A facile approach for the preparation of cis‐3‐methyl‐4‐aminopiperidine derivatives is described. The synthesis was carried out via regioselective ring opening of N‐benzyl‐3‐methyl‐3,4‐epoxi‐piperidine (8), which can be easily obtained in two steps from the corresponding N‐benzyl‐pyridinium salt (5). Seven new cis‐3‐methyl‐4‐amino and amido piperidines compounds were obtained.     

Facile Synthesis of 3,3‐Dialkyl‐6‐phenyl‐imidazopyridinones

A series of novel 3,3‐dialkylated imidazopyridinones bearing 6‐aryl groups were designed as mimetics of active progesterone antagonists, 3,3‐disubstituted‐5‐arylindoles. The four‐step synthetic route is described. The key steps are base‐catalyzed cyclization, base‐catalyzed alkylation, and Suzuki coupling reaction.     

A New Synthesis of 5,8‐Dimethyl‐2‐tetralone—A Potential Intermediate for the Synthesis of Ring‐A Aromatic Sesquiterpenes. Novel Transformation During Acetoxylation of 5,8‐Dimethyldihydronapthalene

Abstract

An efficient synthesis of 5,8‐dimethyl‐2‐tetralone 4 starting from 5,8‐dimethyl‐1‐tetralone 2 is described. It was converted into the unsaturated derivative 3, which on epoxidation followed by acid hydrolysis yielded tetralone 4. Acetoxylation of 3 with manganese(III) acetate and potassium bromide afforded dimethylnaphthalene 8 and derivative 9.     

Practical Synthesis of 2,3,4,5‐Tetramethoxytoluene

The title compound, a key material for synthesis of coenzyme Q₁₀, was effectively prepared in high yield by a reaction sequence starting from 3,4,5‐trimethoxybenzadehyde via Wolff–Kishner reduction, Vilsmeier–Haack reaction, Dakin reaction, and methylation.     

Synthesis of (±)‐ar‐Macrocarpene

An efficient first synthesis of the sesquiterpene ar‐macrocarpene, an irregular sesquiterpene isolated from Cupressus macrocarpa foliage, starting from 3‐methylcyclohexenone has been described, which confirmed the structures of macrocarpenes.     

Facile Synthesis of 2‐Substituted 4‐Azaindoles

A novel and efficient strategy for the synthesis of 2‐substituted 4‐azaindoles from 2‐chloro‐3‐nitropyridine through Pd‐catalyzed Sonogashira cross‐coupling, followed by reduction and heteroannulation on t‐BuOK, is reported.     

Microwave‐Assisted Synthesis of Azocalixarenes

Five new water‐soluble and two water‐insoluble azocalixarenes have been synthesized by coupling reaction of different substituted anilines and terta hydroxylcalix[4]arene. These dyes have been characterized by ¹H NMR, ¹³C NMR, FAB mass, and elemental analysis.     

Practical Synthesis of 3‐Carboxyindazoles

A clean, high‐yielding synthetic route to methyl 5‐(bromomethyl)‐1‐tritylindazole 3‐carboxylate 1 was needed. A principal intermediate was 5‐methyl‐3‐carboxyindazole 2. An analysis of a by‐product found after executing Schad's 3‐carboxyindazole synthesis led to undertaking this reaction with an inverse addition in the principal step. This simple modification gave 2 in excellent and reproducible yields.     

Facile Synthesis of 3,6‐Diaminopyridazine

An efficient two‐step synthesis of 3,6‐diaminopyridazine from 3,6‐dichloropyridazine is reported. In this synthetic procedure, 4‐methoxybenzylamine was used as a nitrogen source to substitute the chloro groups of 3,6‐dichloropyridazine to form N,N′‐bis‐(4‐methoxybenzyl)‐pyridazine‐3,6‐diamine. The 4‐methoxybenzyl groups were then removed by treatment with hydrochloric acid to provide the target 3,6‐diaminopyridazine with an overall yield of 78%.     

Synthesis of Novel Derivatives of Pyridine‐2,6‐dicarboxylic Acid

Two series of novel derivatives of pyridine‐2,6‐dicarboxylic acid with potential as polydentate ligands were synthesized from pyridine‐2,6‐dicarboxylic acid. All new compounds were characterized by NMR, MS, IR, and EA.     

Microwave‐Assisted One‐Pot Synthesis of 1,2,3,4‐Tetrahydrocarbazoles

A series of 1,2,3,4‐tetrahydrocarbazoles 3a–m were synthesized by the reaction of substituted 2‐bromocyclohexanones 2a–c with appropriate anilines 1a–i under microwave irradiation without any other catalysts.     

Efficient Synthesis of Substituted 2‐Amino‐3‐carbethoxythiophenes

A microwave‐assisted method for the synthesis of a variety of thiophene o‐aminoesters (2a–l) has been developed, starting from an appropriate aldehyde, methyl ketone or acetoacetate ester with ethyl cyanoacetate in the presence of elemental sulfur.     

Convenient Synthesis of Some Substituted 5‐Oxonitriles under Aqueous Conditions: Synthesis of 3,4‐Dihydro‐2H‐pyrrole‐2‐carbonitriles

Michael additions of [(diphenylmethylene)amino]acetonitrile (1) to α,β‐unsaturated ketones (chalkones) (2) under aqueous conditions allow for the highly diastereoselective synthesis of substituted 2‐amino‐5‐oxonitriles (3). Selective removal of diphenylmethylene protecting group, followed by in situ cyclization, gives 3,5‐diaryl‐3,4‐dihydro‐2H‐pyrrole‐2‐carbonitriles (4).