Total synthesis of topsentolide B2

A stereoselective total synthesis of topsentolide B₂, a selective cytotoxic oxylipin against SK-OV-3 and SK-MEL-2 cancer cell lines has been achieved based on asymmetric dihydroxylation, Roush allylation, and ring closing metathesis (RCM) reactions. The synthesis is completed in 11 steps and 2.1% overall yield.     

Stereoselective synthesis of (1R,2S)-2-amino-1,3-diols from (R)-cyanohydrins

Vinyl substituted (1R,2S)-amino alcohols 5 were obtained by addition of vinyl magnesium bromide to the corresponding cyanohydrin O-trimethylsilyl ethers (R)-2. The O- and N-protected vinyl amino alcohols 6 were ozonized at −78°C in methanol yielding (1R,2S)-2-amino-1,3-diols7 in high enantiomeric and diastereomeric excesses. For purification, compounds 7 in some cases were acetylated to give the derivatives (1R,2S)-8. Racemic 6a was converted by oxidative ozonolysis at −78°C in methanolic NaOH solution to the corresponding methyl N-acetyl-β-hydroxy propanoate 9a. The configuration of (1R,2S)-8a was confirmed by x-ray crystallographic analysis.     

Total synthesis of 3,4-dihydroxyprolines, -threo- -norvaline and (2S,3R,4R)-2-amino-3,4-dihydroxytetrahydrofuran-2-carboxylic acid methyl ester

The Henry reaction between -glyceraldehyde and ethyl nitroacetate allowed the practical development of a diastereoselective synthesis of 3,4,5-trihydroxy-2-nitropentanoic acid esters, which were reduced to polyoxamic acids, which were used in a new diastereoselective synthesis of 3,4-dihydroxyprolines and new enantioselective syntheses of -threo- -norvaline and (2S,3R,4R)-2-amino-3,4-dihydroxytetrahydrofuran-2-carboxylic acid methyl ester.     

Direct low-temperature synthesis of RB6 (R=Ce, Pr, Nd) nanocubes and nanoparticles

Rare-earth hexaborides (RB₆, R=Ce, Pr, Nd) nanocrystals were prepared by a facile solid state reaction in an autoclave. Single-crystalline RB₆ nanocubes were fabricated at 500 °C starting from B₂O₃, RCl₃·6H₂O and Mg powder. RB₆ nanoflakes and nanoparticles could be obtained around 400 °C using NaBH₄ as boron resource. XRD patterns show that all of the hexaborides are cubic phase with high crystallinity and high purity and have lattice parameters that are consistent with nearly stoichiometric products. Raman spectra elucidate the active vibrational modes of the hexaborides. The TEM and FESEM images clearly show that the nanocubes have an average size of 200 nm and nanoparticles of 30 nm. Our experiment developed an efficient, simple and low-cost route to prepare RB₆, which could be extended further to the preparation of other rare-earth metal hexaborides.     

(R)-Oxynitrilase catalyzed synthesis of (R)-ketone cyanohydrins

(R)-Oxynitrilase from almonds (Prunus amygdalus) catalyzes the enantioselective addition of HCN to ethyl alkyl ketones 1 in diisopropyl ether yielding (R)-ethyl alkyl ketone cyanohydrins (R)-2, which are hydrolyzed under acid catalysis to give the -hydroxy acids (R)-3. This (R)-oxynitrilase also catalyzes the enantioselective addition in aqueous citrate buffer (50 mM, pH 4.0), as demonstrated for the preparation of (R)-methyl alkyl ketone cyanohydrins (R)-5 which are obtained in high enantiomeric excesses comparable to those in diisopropyl ether as solvent.     

Stereospecific synthesis of leukotriene B4 (LTB4)

A stereospecific and chirally economical synthesis of LTB₄ starting from 2-deoxy-D-ribose is reported as part of a comprehensive and efficient approach to the Leukotrienes (A, B, C, D, E). The process includes a novel approach to chiral dienic synthons.     

Synthesis of thromboxane A2 analog,dl-(9,11)-methano-(11,12)-amino thromboxane A2

A synthesis of nitrogen containing thromboxane, A₂ analog, $\text{dl}$-(9,11)-methano-(11,12)-amino thromboxane A₂ ($\text{1}$) is described.     

New isosteres of (R)-2-methylhomoserine and (R)-2-methylaspartic acid by alkylation of a chiral imine leading stereoselectively to a quaternary stereogenic center

Imines obtained from either chiral 3-amino-4-silyloxymethylpyrrolidin-2-one 5a or 5b underwent alkylation to give, in good yield and total stereoselection, the corresponding 3,3,4-trisubstituted pyrrolidin-2-ones 8a–d where both the amino and the silyloxymethyl groups lie cis to each other, as shown by ¹H NMR spectroscopic data and NOE experiments. By removal of both the imino group and the chiral inducer from 8b, the pyrrolidin-2-one 12, an isostere of (R)-2-methylhomoserine 2 and the pyrrolidin-2-one 14, an isostere of (R)-2-methylaspartic acid 4 were obtained straightforwardly.     

Triterpene Glycosides from Cussonia paniculata. I. Isolation and Structure Determination of Glycosides A, B1, B2, C, D, G2, H1, and H2 from Leaves of Cussonia paniculata

The 3-O-β-D-glucopyranoside of β-sitosterol (1) and the known triterpene glycosides 3-O-α-L-arabinopyranosides of oleanolic (2a) and ursolic (2b) acids and hederagenin (3), 3-O-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranosideofoleanolic acid (4), 3-O-α-L-arabinopyranosyl-28-O-α-L-rhamnopyranosyl-(1→4)-O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranosides of oleanolic (5a) and ursolic (5b) acids and the newglycoside 28-O-α-L-rhamnopyranosyl-(1→4)-O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranoside of 23-hydroxyursolic acid (6) were isolated from leaves of Cussonia paniculata (Araliaceae). Their structures were established using chemical methods and NMR spectroscopy.__________Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 160–163, March–April, 2005.     

Stereoselective synthesis of (−)-(1R,2S)-2-aminocyclobutane-1-carboxylic acid, a conformationally constrained β-amino acid

The title compound as well as some derivatives have been synthesized for the first time in optically active form by means of a chemoenzymatic transformation used to induce asymmetry in achiral precursors. The enantio- and diastereomeric purity has been determined by HPLC and NMR techniques.     

Asymmetric dihydroxylation route to (R)-isoprenaline, (R)-norfluoxetine and (R)-fluoxetine

An efficient asymmetric synthesis of enantiomerically pure (R)-isoprenaline, (R)-norfluoxetine and (R)-fluoxetine is described using Sharpless asymmetric dihydroxylation as the key step.     

A new sample preparation and separation combination for precise,accurate, rapid,and simultaneous determination of vitamins B1, B2, B3, B5, B6, B7, and B9 in infant formula and related nutritionals by LC-MS/MS

An improved method was developed for simultaneous determination of the fortified forms of thiamine (B₁), riboflavin (B₂), nicotinamide and nicotinic acid (B₃), pantothenic acid (B₅), pyridoxine (B₆), biotin (B₇), and folic acid (B₉) in infant formulas and related nutritionals. The method employed a simple, effective, and rapid sample preparation followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). It improved upon previous methodologies by offering facile and rugged sample preparation with improved chromatographic conditions, which culminated in a highly accurate and precise method for water-soluble vitamin determination in a wide range of formulas. The method was validated over six days in ten unique matrices with two analysts and on instruments in two different labs. Intermediate precision averaged 3.4 ± 2.6% relative standard deviation and over-spike recovery averaged 100.2 ± 2.4% (n = 160). Due to refinements in sample preparation, the method had high sample throughput capacity.     

Preparation of chiral diimino- and diaminodiphosphine ligands and their Cu and Ag complexes. X-ray crystal structures of [Cu(1S,2S-cyclohexyl-P2N2)][PF6] and [Ag(1R,2R-cyclohexyl-P2N2H4)][BF4]

The interaction of optically pure 1R,2R-diammoniumyclohexane mono-(+)-tartrate and 1S,2S-diammoniumcyclohexane mono-(−)-tartrate with 2 equiv. of o-(diphenylphosphino)benzaldehyde in the presence of 2 equiv. of potassium carbonate in a refluxing ethanol/water mixture gave the optically pure condensation products N,N′-bis[o-(diphenylphosphino)benzylidene]-1R,2R-diiminocyclohexane[1R,2R-cyclohexyl-P₂N₂, (R,R)-I] and N,N′-bis[o-(diphenylphosphino)benzylidene]-1S,2S-diiminocyclohexane [1S,2S-cyclohexyl-P₂N₂, (S,S)-I], respectively, in good yield. Reduction of optically pure (R,R)-I and (S,S)-I with NaBH₄ in ethanol gave the optically pure reduced products N,N′-bis[o-(diphenylphosphino)benzylidene]-1R,2R-diaminocyclohexane[1R,2R-cyclohexyl-P₂N₂H₄, (R,R)-II] and N,N′-bis[o-diphenylphosphine)benzylidene]-1S,2S-diaminocyclohexane[1S,2S-cyclohexyl-P₂N₂H₄, (S,S)-II], respectively, in good yield. The coordination behaviour of I and II toward salts of Cu^I and Ag^I have been examined. The interaction of [Cu(C)₃CN)₄][X] (X = ClO₄⁻, PF₆⁻) with 1 equiv. of optically pure L₄ [L₄ = (R,R)-I, (S,S)-I, (R,R)-II and (S,S)-II] gave the corresponding optically pure [CuL₄][X] complexes, III–VI IIIa, L₄ = (R,R)-I, X = PF₆⁻ IIIb, L₄ = (R,R)-I, X = ClO₄⁻ IV, X = PF₆⁻; Va, L₄ = (R,R)-II, X = PF₆⁻, Vb L₄ = (R,R)-II, X= ClO₄⁻, VI L₄ = (S,S)-II, X = PF₆⁻, in good yield. For the Cu^I complexes, the L₄ ligand acted as a tetradentate ligand. However, a variable-temperature ³¹P[¹H] NMR study of IIIb shows that at ambient temperature one of the imino groups of the tetradentate ligand undergoes rapid dissociation to form a tridentate ligand. The interaction of AgBF₄ with 1 equiv. of otpically pure L₄ [L₄ = (R,R)-I, (S,S)-I, (R,R)-II and (S,S)-II gave the corresponding optically pure [AgL₄][BF₄] complexes, VII–X VII L₄ = (R,R)-I; VIII, L₄ = (S,S)-I; IX,L₄ = (R,R)-II; X, L₄ = (S,S)-II], in good yield. For the Ag^I complexes, the L₄ ligand acted as a tetradentate ligand with the two amino groups coordinated unsymmetrically to the silver. A variable temperature ³¹P [¹H] NMR study of VII suggests that at high temperature the complex exists as a tri-coordinated complex. The structurers of IV and IX were established by X-ray diffraction studies.