Regio- and stereospecific [3+2] cycloaddition of an unusual nitrone derived from a N-hydroxy-2-pyridone with medium ring enones

Regio- and stereospecific 1,3-dipolar cycloaddition of the nitrone derived from a N-hydroxy-2-pyridone 6 with Z-2-cyclodecenone 7a was accomplished, thus substantiating a possible biomimetic route to pyridomacrolidin 2 from pyridovericin 1 and cephalosporolide B 5. This reaction was further exemplified with different enones (7a-g) similar to cephalosporolide B 5. In all the cases the cycloaddition occurred with high regiochemical control and with high retention of alkene geometry. Both endo and exo modes of cycloaddition were observed. This process can also be extended to aryl conjugated enones as long as no enolisable hydrogens are present.     

An efficient synthesis of 1,4-dideoxy-1,4-imino-d- and l-arabinitol and 1,4-dideoxy-1,4-imino-d- and l-xylitol from chiral aziridines

A highly efficient method for the synthesis of 1,4-dideoxy-1,4-imino-d- and l-arabinitol (d-AB1, 1 and l-AB1, 3) and 1,4-dideoxy-1,4-imino-d- and l-xylitol (d-DIX, 2 and l-DIX, 4) starting from commercially available chiral aziridines was developed. The general strategy employs a sequence involving two-carbon homologation, dihydroxylation, and regioselective aziridine ring opening/intramolecular five-membered iminosugar ring formation. The facile use of recrystallization to generate pure diastereomers makes the routes more amenable to large-scale synthesis.     

Enantioselective synthesis of d- and l-α-methylcysteine with hydantoinase

A scalable and cost-effective synthesis of d- and l-α-methylcysteine is described. A key step is d-selective cyclization of N-carbamoyl S-tert-butyl-d,l-α-methylcysteine catalyzed by hydantoinase. d-5-tert-Butylthiomethyl-5-methylhydantoin and N-carbamoyl S-tert-butyl-l-α-methylcysteine were obtained with excellent yield and optical purity, and these compounds were easily separated by filtration. After hydrolysis and cleavage of the tert-butyl group, d- and l-α-methylcysteine hydrochloride were obtained.     

Regio- and stereoselective syntheses of l-pentose derivatives from l-arabinose

Novel l-arabinose, l-ribose, 2-deoxy-l-ribose and 2-fluoro-2-deoxy-l-arabinose derivatives were synthesized from readily available l-arabinose. Different synthetic routes to methyl 3,5-di-O-acylated-l-arabino(ribo)furanosides as valued intermediates for the preparation of C-2 functionalized l-pentoses were investigated via regioselective transformations of 1,2-di-O-acetyl-3,5-di-O-pivaloyl-l-arabinofuranose, and selective acylation of methyl l-arabinofuranoside with 4-chlorobenzoyl or pivaloyl chloride. Short three-five-step syntheses of methyl 2-deoxy-α-l-ribofuranoside, its 3,5-di-O-acyl derivatives, valuable precursors for preparation of antiviral 2′-deoxy-l-nucleosides, were accomplished via simple and efficient reduction of methyl 2-O-mesyl-l-arabinofuranoside with L-Selectride or tandem reaction involving a complex hydride 2-deoxygenation/acylation of intermediate 2-deoxysugar. A new synthesis of 2′-deoxy-2′-fluoro-β-l-arabinofuranosyl thymine (l-FMAU) was performed using a mild fluorination of protected l-ribofuranoside and a novel sequence of conversions for the preparation of 2-deoxy-2-fluoro-l-arabinofuranoside derivatives.     

A method for the stereospecific synthesis of chiral cis-2-alkylcyclopropyllithium reagents

A general synthetic route to optically active $\text{cis}$-1,2-disubstituted cyclopropanes has been developed from the key intermediates 3 and 4.     

Regioselective phosphorylation of vicinal 3,4-hydroxy myo-inositol derivative promoted practical synthesis of d-PtdIns(4,5)P2 and d-Ins(1,4,5)P3

The reactivity of 3 and 4-OH in 3,4-diol myo-inositol derivatives were observed through the phosphorylation, acylation and silylation. The results indicated that 3-OH is much more reactive than 4-OH, giving regiospecifically 3-mono-functionalized products. This investigation provided a concise methodology for the synthesis of natural d-form of PtdIns(4,5)P2 and d-Ins(1,4,5)P3 from l-1,2-O-cyclohexylidene-3,4-O-(tetraisopropyl disiloxane-1,3-diyl)-myo-inositol.     

Novel synthesis of 5-thio-hexopyranoside: preparation of 5-thio-d- and l-glucose and 1,6-anhydro-5-thio-l- and d-altrose

Asymmetric synthesis of both d- and l-isomers of 5-thioglucose and 1,6-anhydro-5-thioaltrose are described. The key intermediates, l- and d-threose diethylacetal derivatives, were derived by chemical transformation from d-xylose or d-arabinose and by Sharpless asymmetric dihydroxylation from γ-hydroxycrotylaldehyde diethylacetal. They transformed to γ-thiiranyl diethylacetal via trans-2,3-epoxy alcohol in seven steps. Acetic acid-promoted cyclization of γ-thiiranyl diethylacetal gave 5-thiopyranoside. Removal of the protected groups under the acidic conditions afforded 5-thio-d- and l-glucose and 1,6-anhydro-5-thio-l- and d-altrose, respectively.     

Sulfonate protecting groups. Synthesis of O- and C-methylated inositols: d- and l-ononitol, d- and l-laminitol, mytilitol and scyllo-inositol methyl ether

Syntheses of d- and l-ononitol, d- and l-laminitol, mytilitol and scyllo-inositol methyl ether starting from myo-inositol are described. One or two of the myo-inositol 1,3,5-orthoformate hydroxyl groups were protected as tosylates. These mono or ditosylates served as key intermediates for the preparation of O- and C-methyl inositols. Racemic 2,4-di-O-tosyl-myo-inositol 1,3,5-orthoformate was resolved as its diastereomeric camphanates. Use of sulfonate groups for the protection of inositol hydroxyl groups resulted in substantial improvement in the overall yield of O- and C-methyl inositols.     

Total synthesis of d-(+)-biotin

A total synthesis of d-(+)-biotin is described starting from d-(+)-glucosamine using acyliminium chemistry.     

Practical synthesis of d-[1-C]mannose, l-[1-C] and l-[6-C]fucose

The chemical synthesis of ¹³C-labeled mannose and fucose is important for the preparation of molecular probes used in the conformational study of the oligosaccharide portions of glycoproteins. A new method for the synthesis of the title [1-¹³C]-labeled compounds via the corresponding olefin compounds, which are in turn derived from d-mannitol or l-arabinose by efficient introduction of ¹³C, by the Wittig reaction using Ph₃P¹³CH₃I and n-BuLi, is described. The introduction of ¹³CH₃I to produce the [1-¹³C]- and [6-¹³C]-labeled compounds was accomplished in 62%, 56%, and 71% yields, respectively. All mannose and fucose protons, from H-1 to H-6, were observed by the HMQC-TOCSY technique using 1:1 mixtures of [1-¹³C]- and [6-¹³C]-labeled compounds.     

Stereospecific synthesis of Z- and E-1 alkoxy-1,3-butadienes

A stereospecific, highly efficient, generally applicable synthesis of $\text{Z}$- and $\text{E}$-1-alkoxy-1,3-butadienes involving dehydrative decarboxylations of 4,5-unsaturated-2-alkoxy-3-hydroxy-carboxylic acids is described.     

A general strategy for the stereoselective synthesis of l-1-deoxyallonojirimycin and d-1-deoxygulonojirimycin

A general strategy for the synthesis of deoxyazasugars from d-glucose is described. Ring-closing metathesis and stereoselective dihydroxylation reactions were used as key steps.     

Direct synthesis of the antitumor agent erythro-α-amino-3-bromo-4,5-dihydroisoxazole-5-acetic acid

Generation of bromonitrile oxide in the presence of vinylglycine leads to the formation of the title compound $\text{2}$ and its $\text{threo}$ isomer in good yield.     

An efficient synthesis of d-ribo- and l-lyxo-phytosphingosine from d-tartaric acid

The preparations of d-ribo- and l-lyxo-phytosphingosines (1, 2) are described. Chelation-controlled addition of tetradecylmagnesium bromide to pentylidene-protected d-threitol aldehyde 6 afforded the key intermediate tetrol 7, providing the desired l-lyxo stereochemistry of phytosphingosine. Inversion at C4 of intermediate 7 provided the d-ribo stereochemistry.     

Concise synthesis of orthogonally diprotected l-glyceraldehyde

Orthogonally diprotected l-glyceraldehyde was efficiently prepared from readily available starting materials, allowing to obtain a highly stable and synthetically versatile chiral building block compared to known symmetrically protected derivatives.     

d- and l-Erythrose as sources of chiral quaternary carbon centers. Total synthesis of (−)-malyngolide and (+)-tanikolide

A highly efficient and versatile approach was applied for the total synthesis of the marine natural products (−)-malyngolide and (+)-tanikolide from isopropylidene l- and d-erythrose, using a common strategy.     

Stereospecific synthesis of a dl-gala-aminoquercitol derivative

A new aminoquercitol derivative was synthesized starting from 1,4-cyclohexadiene. Photooxygenation of cyclohexa-1,4-diene afforded anti-2,3-dioxabicyclo[2.2.2]oct-7-en-5-yl hydroperoxide as the main product. The formed hydroperoxy endoperoxide was reduced with LiAlH₄ to produce anti-2,3-dioxabicyclo[2.2.2]oct-7-en-5-ol. Protection of alcohol with acetyl chloride followed by reduction of the endoperoxide with thiourea, and then palladium-catalyzed ionization/cyclization reaction gave an oxazolidinone derivative. Hydrolysis of the oxazolidinone ring and acetylation gave an amino compound. Oxidation of the double bond in the amino compound with OsO₄ followed by acetylation gave the amino tetraacetate and removal of the acetate groups furnished the desired aminoquercitol whose exact configuration was determined by X-ray diffraction analysis.     

Asymmetric syntheses of 2,5-dideoxy-2,5-imino-d-glucitol [(+)-DGDP] and 1,2,5-trideoxy-1-amino-2,5-imino-d-glucitol [(+)-ADGDP]

The asymmetric syntheses of 2,5-dideoxy-2,5-imino-d-glucitol [(+)-DGDP] and 1,2,5-trideoxy-1-amino-2,5-imino-d-glucitol [(+)-ADGDP] were achieved via the ring-closing iodoamination of an enantiopure bishomoallylic amine, followed by functionalisation of the resultant iodomethyl substituted pyrrolidine. In the case of (+)-DGDP, formation of the corresponding aziridinium ion followed by regioselective ring-opening with H₂O gave the desired hydroxymethyl substituted pyrrolidine as a single diastereoisomer (>99:1 dr), with subsequent deprotection giving (+)-DGDP in good yield. Whereas in the case of (+)-ADGDP, displacement of iodide with NaN₃ proved to be optimal, giving (+)-ADGDP in good yield after reduction and deprotection.