Synthesis of (2<Emphasis Type="Italic">S</Emphasis>,3<Emphasis Type="Italic">S</Emphasis>,4<Emphasis Type="Italic">S</Emphasis>)-2,3-<Emphasis Type="Italic">O</Emphasis>-isopropylidene-4-(methoxycarbonylmethyl)cyclopentan-1-one

(2S,3S,4S)-2,3-O-Isopropylidene-4-(methoxycarbonylmethyl)cyclopentan-1-one was synthesized starting from D-ribose through methyl (Z)-3-(5-acetyl-2,2-acetoxyacetyl-2,2-dimethyl-1,3-dioxolan-4-yl)prop-2-enoate which was subjected to cyclization in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene, followed by decarboxylation.     

Synthesis,crystal structure and optical properties of A3Zr2P5S18 (A=Rb,Cs): the first quaternary zirconium thiophosphates

The first quaternary zirconium thiophosphates Rb₃Zr₂P₅S₁₈ (1) and Cs₃Zr₂P₅S₁₈ (2) were synthesized by reacting ZrS₂ with an in situ formed melt of A₂S₃ (A=Rb, Cs), P₂S₅ and S. The compounds are isostructural and crystallize in the monoclinic space group Cc with Z=4. Compound 1 has cell parameters a=9.248(2) Å, b=9.860(2) Å, c=33.622(7) Å and β=94.73(3)° and compound 2 a=9.288(2) Å, b=9.956(2) Å, c=34.061(7) Å and β=94.26(3)°. The structures are composed of a two-dimensional anionic layer [Zr₂P₅S₁₈]³⁻ and intervening alkali cations. Each of the two independent Zr atoms is surrounded by seven S atoms yielding a distorted pentagonal bipyramid. The ZrS₇ polyhedra are interconnected into the final layered anion by [P₂S₇] groups which act in an unusual edge- and corner-sharing mode and by edge-sharing [PS₄] tetrahedra. Compound 2 was characterized with MIR and UV/vis diffuse reflectance spectroscopy.     

Stereoselective production of (S)-1-aralkyl- and 1-arylethanols by freshly harvested and lyophilized yeast cells

Substituted (S)-1-phenyl- 2a–h and (S)-1-benzyl-propan-2-ols 4a and b, and (S)-1-phenylethanol 6 were produced from prochiral ketones 1a–h, 3a,b and 5 by reductions with freshly harvested Zygosaccharomyces rouxii and Debaryomyces hansenii cells. The bioreductions were also performed by lyophilized cells. Comparison of the secondary alcohols from the bioreductions 2b–e,g,h and 4a and authentic (S)-alcohols (S)-2b–e,g,h and (S)-4a synthesized from enantiopure (S)-methyloxirane 7 proved the absolute configuration of the products.     

Highly efficient resolutions of 1,4-benzodioxane-2-carboxylic acid with para substituted 1-phenylethylamines

The salts of (S)- and (R)-1,4-benzodioxane-2-carboxylic acid with eight (S)-1-arylethylamines were prepared. The determination of their melting points and of their solubilities in alcohol solvents revealed large differences between the diastereomeric benzodioxanecarboxylates of (S)-1-(p-nitrophenyl)ethylamine and of (S)-1-(p-methylphenyl)ethylamine. Therefore, these latter amines were selected to resolve (±)-1,4-benzodioxane-2-carboxylic acid by diastereoselective crystallization finding that both of them display a very high resolution ability for such a substrate, which contrasts with the null efficiency of unsubstituted 1-phenylethylamine. These results are consistent with DSC evidences, which indicated that the two successfully resolved diastereomeric systems are binary mixtures exhibiting a eutectic with a high content of the more soluble diastereomeric salt. The new procedures can advantageously replace the two resolutions we had previously reported, that of the same acid with dehydroabietylamine and that of glycerol acetonide, a precursor of 1,4-benzodioxane-2-carboxylic acid, with 1-phenylethylamine.     

Resolution of 1-phenyl-2-(p-tolyl)ethylamine via diastereomeric salt formation

(S)-1-Phenyl-2-(p-tolyl)ethylamine (S)-1, used for the industrial scale resolution of chrysanthemic acids, was obtained via resolution of the racemate with the hemiphthalate of (S)-isopropylidene glycerol (R)-2. The maximum experimental efficiency [69% yield and >99% e.e. of (S)-1] was achieved by a simple precipitation of (S)-1·(R)-2 from the solution of the 1:1 diastereomeric salt mixture in 93/7 isopropanol/water at saturation of the more soluble (R)-1·(R)-2 salt. Such an experimental efficiency was consistent with 0.79 maximum theoretical resolvability, derived from the solubilities of the two diastereomeric salts, and with DSC data, which indicated that the (S)-1·(R)-2/(R)-1·(R)-2 system is a binary mixture exhibiting an eutectic with composition approximately corresponding to a 0.2 molar ratio of (S)-1·(R)-2.     

First chiral synthesis of the N-terminal amino acid congener of nikkomycin Z based on lipase-catalyzed enantioselective acetylation of a primary alcohol possessing two stereogenic centers

A stereoselective synthesis of a versatile chiral synthon possessing two stereogenic centers, (2S,3S)-3-[2-(5-benzyloxypyridyl)]-2-methyl-1,3-propane diol 12 (>99% ee), was achieved by using a chemo-enzymatic method. The conversion of (2S,3S)-12 to the homochiral intermediate (2S,3S,4S)-2-benzyloxycarbonylamino-4-[2-(5-benzyloxypyridyl)]-4-tert-butyldimethylsilyloxy-3-methylbutanoic acid 2 corresponding to the N-terminal amino acid congener of nikkomycin Z 1 is described.     

Preliminary studies on a novel synthesis of β-amino acids: stereocontrolled transformation of d- and l-glyceraldehyde into 3-amino-2-(2′,2′-dimethyl-1′,3′-dioxolan-4′-yl)propanoic acids

A stereocontrolled synthesis of the methyl ester of (2S)-3-amino-2-((4′S)-2′,2′-dimethyl-1′,3′-dioxolan-4′-yl)propanoic acid from d-glyceraldehyde is described for the first time. This method involves the stereoselective Michael addition of the lithium salt of tris(phenylthio)methane to (S)-2,2-dimethyl-4-((E)-2-nitrovinyl)-1,3-dioxolane followed by hydrolysis of the resulting (4S)-2,2-dimethyl-4-((2′S)-3′-nitro-1′,1′,1′-tris(phenylthio)propan-2′-yl)-1,3-dioxolane to (2S)-methyl 2-((4′S)-2′,2′-dimethyl-1′,3′-dioxolan-4′-yl)-3-nitropropanoate, which was finally reduced to the target compound. A similarly stereocontrolled transformation of l-glyceraldehyde into (2R)-methyl 3-amino-2-((4′R)-2′,2′-dimethyl-1′,3′-dioxolan-4′-yl)propanoate is also described.     

Synthesis of both syn and anti diastereoisomers of Boc-dolaproine from (S)-proline through DKR using ruthenium-catalyzed hydrogenation: a dramatic role of N-protecting groups

The natural (2R,3R)-Boc-dolaproine and its unnatural (2S,3S) diastereoisomer were synthesized involving as key transformation the Ru(II)-promoted hydrogenation of the β-keto-α-methyl ester derived from (S)-N-Boc-proline. Interestingly, the asymmetric hydrogenation of this β-keto ester N-protected as an amine hydrochloride salt, provided the corresponding anti (2S,3R)- and (2R,3S)-β-hydroxy-α-methyl esters with significant level of selectivities through dynamic kinetic resolution.     

Synthesis of (-)-2s,3s, 11s,12r-2,3,11,12-tetraphenyl[18]crown-6

The synthesis of ( - ) 2S,3S,11S,12R-2, 3,11,12-tetraphenyl [18]-crown-6 from (-)-1S,2S-hydrobenzoin and meso-hydrobenzoin is described. Chemical shifts and vicinal coupling constants of the benzylic protons in the 2 S, 3 S and 11 S,12 R substructures in the free ligands and in complexes with KSCN and 1-phenylethylammonium bromides and a brief discussion of the related conformational changes are also presented. A detailed procedure for the resolution of racemic hydrobenzoin is given.     

Die Reaktionen von Trithiazylchlorid mit Zirkoniumtetrachlorid Die Kristallstruktur von (S4N4CI)2[Zr2CI10]

Reactions of Zirconium Tetrachloride with Trithiazylchloride. Crystal Structure of (S₄N₄)[Zr₂Cl₁₀] Zirconium tetrachloride reacts with (NSCI)₃ yielding (S₃N₃CI₂)₂[Zr₂CI₁₀], S₄N₄[Zr₂CI₁₀], or (S₄N₄CI)₂[Zr₂CI₁₀], depending of the reaction conditions. These compounds were characterized by their i.r. spectra. They have an ionic structure containing the known ions S₃N₃CI₂⊕, S₄N₄^2⊕, S₄N₄CI^⊕, and the thus far unknown [Zr₂CI₁₀]^2? ion. According to the X-ray structure determination (2827 independent observed reflexions, R = 0.027), (S₄N₄CI)₂[Zr₂CI₁₀] crystallizes in the space group P&1macr; with the lattice constants a = 688, b = 1132, c = 1827 pm, α = 103.2°, β = 98.7° and γ = 91.9⁰ and with Z = 2 formula units per unit cell. The structure is built up from S₄N₄CI^⊕ ions, which are nearly identical as in S₄N₄CI[FeCI₄] and from [Zr₂CI₁₀]^2? ions in which two chloro bridges join two edge-sharing octahedra.     

Resolution of racemic R.S-α-arylethylamine by a new resolving agent (R)thiazolidine-2-thione-4-carboxylic acid

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NaZr2N2SCl: Ein flußmittelstabilisiertes Derivat von Zirconium(IV)–Nitridsulfid (Zr2N2S)

NaZr₂N₂SCl: A Flux‐Stabilized Derivative of Zirconium(IV) Nitride Sulfide (Zr₂N₂S) The oxidation of zirconium metal with elemental sulfur and sodium azide (NaN₃) should give access to zirconium(IV) nitride sulfide, Zr₂N₂S, which could crystallize isotypically with the trigonal rare‐earth(III) oxide sulfides M₂O₂S (M = Y, La–Lu). Appropriate molar admixtures of these reactants together with NaCl added as flux were heated for seven days at 850 °C in torch‐sealed evacuated silica tubes. As main product, however, pale yellow platelets with the composition NaZr₂N₂SCl (trigonal, R 3 m; a = 363.56(3), c = 2951.2(4) pm; Z = 3) emerged as single crystals. This pseudo‐quaternary compound crystallizes isotypically with e. g. Li_xEr₂H_yCl₂ (x ≤ 1, y ≤ 2) in a (doubly) stuffed ZrBr‐type structure and contains at least structural domains of the hypothetical Ce₂O₂S‐analogous Zr₂N₂S. Zr⁴⁺ resides in monocapped trigonal anti‐prismatic sevenfold coordination of the anions (d(Zr–N) = 218 (3 ×) and 220 pm (1 ×), d(Zr–S/Cl) = 266 pm, 3 ×). Closest packed double‐layers of Zr⁴⁺ with all tetrahedral interstices occupied with N^3– are sandwiched by layers of isoelectronic S^2– and Cl^– anions. These anionic six‐layer slabs (S/Cl–Zr–N–N–Zr–S/Cl) pile up parallel (001) in a cubic closest packed fashion. Charge balance and structural consistence occurs between these layers by intercalation of Na⁺ within octahedral voids (d(Na–S/Cl) = 282 pm, 6 ×) of double‐layers of the indistinguishable heavy anions (S^2– and Cl^–).     

Solid-state structure determination and solution-state NMR characterization of the (2R,4R)/(2S,4S)- and (2R,4S)/(2S,4R)-diastereomers of the agricultural fungicide propiconazole,the (2R,4S)/(2S,4R)-symmetrical triazole constitutional isomer,and a ditriazole analogue

Single-crystal X-ray diffraction analysis was used to determine the structure of a racemic diastereomer of the agricultural fungicide propiconazole [1-(2-(2,4-dichlorophenyl)-4-n-propyl-1,3-dioxolane-2-yl-methyl)-1-H-1,2,4-triazole] and of two by-products (a symmetrical 1,3,4-triazole racemic-constitutional isomer and a propiconazole ditriazole analogue). All three crystalline racemic-diastereomers had (2R,4S)/(2S,4R)-stereochemistry in which then-propyl group was observed in atrans-to-phenyl disposition. Propiconazole (2R,4S)/(2S,4R)-diastereomer gives crystals belonging to the monoclinic space group P2₁,/a, and, at 293 K,a=8.1192(3),b=18.9769(6),c=10.7137(4) å,Β=99.765(3)?,V=1626.8(1) å³, Z=4,R(F)=0.060, andR _w(F)=0.058. The constitutional isomer by-product (2R,4S)/(2S,4R)-1-(2-(2,4-dichlorophenyl)-4-n-pro-pyl-1,3-dioxolane-2-yl-methyl)-1-H-1,3,4-triazole gives crystals belonging to the monoclinic space group P2₁/n, and, at 293 K,a=11.1763(6),b=10.7716(4),c=14.5804(8) å,Β=107.445(4)?,V=1674.6(1) å³, Z=4,R(F)=0.043, andR _w(F)=0.043. The ditriazole byproduct (2R,4S)/(2S,4R)-1-(2-(2-chloro-4-(1,2,4-triazole-1-yl)phenyl)-4-n-propyl-1,3-dioxolane-2-yl-methyl)-1-H-1,2,4-triazole gives crystals belonging to the triclinic space groupP¯ 1, and, at 193 K,a=5.3329(8),b=8.3738(7),c=20.240(2) å, α=84.213(6)?,Β=87.20(1)?,γ=86.23(1)?,V=896.5(2) å³, Z=2,R(F)=0.046, andR _w(F)=0.051. The presence of both propiconazole (2R.4S)- and (2S,4R)-enantiomers enables the formation of a crystalline racemic modification, while the diastereomeric propiconazole (2R,4R)- and (2S,4S)-enantiomers are viscous oils. In the absence of its enantiomorphic partner, the propiconazole (2R,4S)- or (2S,4R)-enantiomers remain as viscous oils rather than form chiral crystals.     

A practical synthesis of enantiopure β-methyltryptophan ethyl ester for a preparation of diabetes drug

A practical synthesis of (2R,3S)- and (2S,3R)-β-methyltryptophan ethyl ester (β-MeTrp-OEt) has been developed. Racemic threo-β-MeTrp-OEt was diastereoselectively prepared via crystallization-induced diastereomer transformation (CIDT) of the α-nitro equivalent of β-MeTrp-OEt. The enantiomers were resolved via diastereomeric salt formation using a half equivalent of (R)-2-(4-hydroxyphenoxy)propionic acid. The process allowed a diabetes drug candidate N-[(1R,2S)-1-({5-[(dimethylamino)methyl]-2-ethoxyphenyl}aminocarbonyl)-2-(1H-indol-3-yl)propyl]-4-phenyl-1-piperidinecarboxamide to be prepared in good yield with high quality.     

Synthesis of N-allyl- and N-acyl-2-vinylindoline

Heating a mixture of (2R*,3R*)- and (2R*,3S*)-2-[(1S*)-1-iodoethyl]-3,5-dimethyl-1-[(2-nitrophenyl) sulfonyl]indolines with N-isopropylpiperidine in xylene resulted in (2S*,3R*)-3,5-dimethyl-1-[(2-nitrophenyl) sulfonyl]-2-vinylindoline. The latter reacted with thiophenol to afford (2S*,3R*)-3,5-dimethyl-2-vinylindoline, whose reaction with allyl halides or acetyl bromide gave rise to N-allyl-, N-propenyl-, or N-acetyl derivatives. Nitration of 1-acetyl-3,5-dimethyl-2-vinylindoline yielded ortho-nitro derivative.     

Intercalating nucleic acids: The inversion of the stereocenter in 1-O-(pyren-1-ylmethyl)glycerol from R to S. Thermal stability towards ssDNA, ssRNA and its own type of oligodeoxynucleotides

The synthesis and insertions of (S)-1-O-(pyren-1-ylmethyl)glycerol into intercalating nucleic acids is described. Insertions of this S-isomer as a bulge lead to reduced binding affinity towards complementary ssDNA compared to intercalating nucleic acids possessing (R)-1-O-(pyren-1-ylmethyl)glycerol in the same positions. Insertions of both (R) or (S) 1-O-(pyren-1-ylmethyl)glycerols as bulges into two complementary strands decreased the stability of the complex compared to dsDNA possessing the pyrene pseudo-nucleotide in one of the strands.     

An efficient synthesis of highly substituted pyrroles from β-oxodithiocarboxylates

α-Oxoketene-N,S-acetals, prepared by the reaction of alkyl glycinate hydrochlorides with β-oxodithiocarboxylates followed by alkylation, underwent cyclization in presence of chloromethyleneiminium salt derived from POCl₃/DMF to afford alkyl-3-aryl-4-formyl-5-(alkylsulfanyl)-1H-pyrrole-2-carboxylates in excellent yields. Alkyl-3-aryl-5-(alkylsulfanyl)-1H-pyrrole-2-carboxylates were formed in moderate yields when the same N,S-acetals were treated with DBU.     

Chromatographic enantioseparation of racemic α-(1-naphthyl)ethylammonium perchlorate by a Merrifield resin-bound enantiomerically pure chiral dimethylpyridino-18-crown-6 ligand

Three novel chiral pyridino-18-crown-6 ligands (S,S)-1, (S,S)-2 and (S,S)-3 were prepared and (S,S)-1 was attached to a Merrifield resin. The resulting adsorbent (S,S)-5 was used as a chiral stationary phase in the chromatographic enantioseparation of racemic α-(1-naphthyl)ethylammonium perchlorate. Also, a new chiral pyridono-18-crown-6 ligand (S,S)-6, used for the synthesis of (S,S)-1 and (S,S)-2, was prepared in two different ways.     

Resolution of 1-cyclohexylethylamine via diastereomeric salt formation with enantiopure 2-phenylacetic acids

The resolution of 1-cyclohexylethylamine 1 with enantiopure 2-phenylacetic acids via diastereomeric salt formation was investigated. (R)-2-Methoxy-2-phenylacetic acid 3 and the (S)-2-phenylpropionic acid 5 were found to be efficient resolving agents for obtaining the single enantiomer (S)-1 as the correspondingly less-soluble diastereomeric salt (resolution efficiency = 48% and 52%, respectively).     

Synthesis of a diastereomeric mixture of deuterium-labeled lovastatin and its acid ammonium salt

In this communication, a facile synthesis for (2S/2R)-[²H₃]lovastatin and (2S/2R)-[²H₃]lovastatin acid ammonium salt was described. The stable isotope-labeled (2S/2R)-lovastatin and its acid ammonium salt were prepared from butyric acid via several reaction steps with 11.1 and 6.3 % overall yield, respectively.