An efficient and simple synthesis of (−)-wine lactone

A, short and efficient diastereoselective synthesis of (−)-wine lactone (−)-4a involving FeCl₃/NaI-mediated iodolactonization of γ,δ-unsaturated acid 7 as the key step is described.     

An efficient and practical asymmetric synthesis of (−)-tasimelteon

Tasimelteon is a useful drug for the treatment of Non-24 in totally blind individuals. An efficient and convenient asymmetric synthesis of tasimelteon has been developed from 4-vinyl-2,3-dihydrobenzofuran through six steps in 53% overall yield using the Corey–Bakshi–Shibata (CBS0 asymmetric reduction of ketone as a key step.     

An efficient synthesis of (R)-(−)-baclofen

In this report we describe an efficient synthesis of (R)-(−)-baclofen, a selective GABA_B agonist used as an antispastic agent. Our strategy is based on an enantioselective deprotonation of a cyclobutanone easily obtained by [2+2] cycloaddition of 4-chlorostyrene and dichloroketene.     

Total synthesis of (−)-phaeosphaeride B by a biomimetic conversion from (−)-phaeosphaeride A

We have accomplished the first total synthesis of STAT3 inhibitory (?)-phaeosphaeride A and its stereoisomer (?)-phaeosphaeride B. This work confirms the configurational assignment of these natural products. Notably, TFA-mediated dehydrative stereoinversion of phaeosphaeride A afforded phaeosphaeride B, based on our hypothesis of the biosynthesis mechanism of phaeosphaeride B from phaeosphaeride A.     

A simple and efficient stereoselective synthesis of (−)-cleistenolide

A simple and straightforward stereoselective synthesis of α,β-unsaturated δ-lactone, (?)-cleistenolide has been accomplished in 10 steps in an overall yield of 19%, starting from inexpensive and commercially available starting materials, respectively. This linear synthesis utilizes Sharpless asymmetric dihydroxylation, sulfur ylide mediated epoxide opening followed by ring-closing metathesis (RCM) for the formation of six-membered lactone ring as the key step sequence.     

An expeditious formal synthesis of (−)-epibatidine

A short route to (−)-epibatidine is described. It includes a hetero-Diels–Alder reaction of a chiral non-racemic acyl-nitroso derivative and 2-t-butyldimethylsilyloxycyclohexadiene followed by chemical manipulations to furnish a known precursor of the natural product in 11% overall yield.     

An efficient synthesis of enantiopure (+)- and (−)-3-exo-amino-7,7-dimethoxynorbornan-2-exo-ols

We describe the synthesis of new amino alcohols (+)- and (−)-3-exo-amino-7,7-dimethoxynorbonan-2-exo-ols. The (+)- or (−)-7,7-dimethoxy-1,4,5,6-tetrachlorobicyclo[2.2.1]hept-5-en-2-endo-ol, obtained from the enzyme catalysed transesterification of the racemate, was reduced and dechlorinated (Na/NH₃; ethanol), followed by pyridinium chlorochromate oxidation of the resultant alcohols to the corresponding ketones. After treatment with t-BuOK/BuONO, in a nitrosation reaction, α-keto oximes were obtained. Reduction over two steps with NaBH₄ and NaBH₄/NiCl₂·6H₂O followed by in situ acetylation furnished the corresponding acetamido esters, which were hydrolysed with CH₃OH/Na to produce the enantiopure amino alcohols in good yields.     

Preparation of modified peptides: direct conversion of α-amino acids into β-amino aldehydes

A direct method for the transformation of α-amino acids into β-amino aldehydes was developed, and applied to the modification of the C-terminal residue of peptides. The method takes place in good yields and under mild conditions. The application of this methodology to the preparation of small peptides with γ-amino alcohol units, which are precursors of analogues of peptaibol antibiotics, is also described.     

An efficient stereocontrolled synthesis of (−)-10-epi-5β,11-dihydroxyeudesmane and (−)-4,10-epi-5β,11-dihydroxyeudesmane

A concise and efficient synthesis of (−)-10-epi-5β,11-dihydroxyeudesmane 1 and (−)-4,10-epi-5β,11-dihydroxyeudesmane 2, via (−)-10-epi-γ-eudesmol 5, was accomplished starting from (+)-dihydrocarvone. The salient feature of our synthesis is the utilization of substrate-directable epoxidation and homogeneous hydrogenation to control the stereochemistry at the C-4 and C-5 positions of the title compounds.     

An expedient conversion of α-amino acids into Weinreb amides using COMU® as a coupling agent

The use of COMU®, as a non-hazardous partner, in the coupling of N-protected α-amino acids to N-methoxy-N-methylamine to afford the corresponding Weinreb amides is discussed. From a practical point of view the reaction can be monitored visually by virtue of the colour change associated with the conversion of substrates (yellow) into the products (orange). As the by-products of the reaction are conveniently water-soluble the products are isolated relatively pure and with minimal racemisation. These factors coupled with the short reaction time make this a very useful procedure.     

Selenium catalyzed conversion of vinyl halides into α-alkoxy acetals

The reaction of vinyl halides with phenylselenenyl chloride in alcohols affords α-alkoxy acetals and diphenyl diselenide which can be oxidized to PhSe cations by nitrate or persulfate anions. The reaction can be carried out with catalytic amounts of PhSeCl or PhSeSePh. The reaction proceeds through the formation of the methoxyselenenylation product which then suffers solvolysis. Under controlled conditions, the 1-phenyl-1-methoxy-2-bromo-2-phenylselenenyl ethane was isolated from the reaction of β-bromostyrene and PhSeCl in methanol. Several deselenenylation reactions of this α-halogenoselenide are reported.     

An efficient synthesis of substituted benzene-1,2-dicarboxaldehydes

Substituted-benzene-1,2-dicarbaldehydes were synthesized by the reaction of substituted-1,2-bis(dibromomethyl) benzenes with fuming sulfuric acid,followed by hydrolysis. The yields were signifi-cantly improved by introducing solid sodium bicarbonate into the reaction mixture before hydrolysis and workup.     

An efficient synthesis of diquinane-based bis-γ-lactones

An efficient stereoselective synthesis of both the diastereomers of diquinane-based conformationally constrained symmetric bis-γ-lactones starting from tricyclic derivative 9 is reported. The key step involves the intramolecular ring opening of an epoxide by the in situ formed hydrate of a diketone leading to the tetracyclic hemiacetal 10, which directly leads to the exo-hydroxy bis-γ-lactone derivatives 2 and 4 under basic hydrogen peroxide cleavage conditions. Conversion to the endo-hydroxy bis-γ-lactone derivatives 1 and 3 was accomplished through lithium hydroxide mediated S_N2 displacements in dimesylate 7, or more expeditiously, via trimesylate 21 through alkaline H₂O₂ mediated cleavage.     

An efficient boric acid-mediated preparation of α-hydroxyamides

An efficient methodology for the preparation of α-hydroxyamides via boric acid-mediated addition of isonitriles onto aldehydes has been developed. The reaction of isonitriles with α-boronobenzaldehyde takes place under intramolecular catalysis conditions to provide functionalized benzoxaboroles.     

Bromodimethylsulfonium bromide: A brominating reagent for the conversion of anthracene into 9,10-dibromoanthracene

Bromodimethylsulfonium bromide(BDMS) was used as an efficient brominating reagent for the synthesis of 9,10-dibromoanthracene in dichloromethane. The desired products were obtained in excellent yields.     

An efficient access to N-tert-butanesulfinyl aldimines in water: Application to one-pot synthesis of homoallylic amines, (+)-crispine A and (−)-coniine

An Efficient method for the syntheses of N-tert-butanesulfinyl aldimines in water was developed using Amberlyst-15 as catalyst. Subsequently, chiral homoallylic amines were synthesized in one pot from aldehydes by combining with In-promoted allylation in aqueous media. The total syntheses of (+)-Crispine A and (?)-Coniine were conducted to demonstrate the utility of this one-pot approach.     

NBS-assisted an efficient conversion of styrenes to α-hydroxy ketones in water

An expedient, mild and environmentally benign method for the oxidation of styrenes to α-hydroxy ketones has been developed. This conversion has been achieved by employing water as a solvent as well as an oxygen source. This facile and efficient tandem process provides α-hydroxy ketones in moderate to good yields from easily accessible styrenes.     

One-pot easy conversion of Baylis-Hillman adducts into carbamates of unsaturated β-amino acids

An easy, one-pot transformation of Baylis-Hillman adducts into carbamates of unsaturated β-amino acids, for example, 2-(aryl(methoxycarbonylamino)methyl)acrylic acid methyl esters 7 and 2-(methoxycarbonyl aminomethyl)-3-arylacrylic acid methyl esters 8 via reaction with the Burgess reagent is described.