First synthesis of (1S,2S)- and (1R,2R)-1-amino-2-isopropylcyclobutanecarboxylic acids by asymmetric Strecker reaction from 2-substituted cyclobutanones

An efficient and easy one-pot reaction from readily available racemic 2-substituted cyclobutanones gave, by means of asymmetric Strecker synthesis in the presence of an amine chiral auxiliary, two major aminonitriles with excellent diastereoselectivity. After separation, the major cis-aminonitriles were hydrolysed and hydrogenolysed to lead for the first time to pure non-racemic (+)-1-amino-2-isopropylcyclobutanecarboxylic acid (ACBC) and its antipode.     

Asymmetric synthesis of nonproteinogenic amino acids with l-amino acid transaminase: synthesis of (2S)-2-amino-4-oxo-4-phenylbutyric and (3E,2S)-2-amino-4-phenylbutenoic acids

2,4-Dioxo-4-phenylbutyric acid and 2-oxo-4-phenylbut-3-enoic acid are converted to the corresponding (S)-2-amino acids by recombinant Escherichia coli whole cells over-expressing aromatic transaminase from Enterobacter sp. BK2K-1 (AroATEs) in high yields (68–78%) and high enantiomeric purity (>99%) using l-aspartic acid as an amino donor.     

Stereoselective synthesis of conformationally constrained (2S,3S)-3-hydroxyornithine

A convenient and efficient route is described for the highly stereoselective synthesis of δ-amino protected and conformationally restricted (2S,3S)-3-hydroxyornithine through the N-benzylnitrone adduct to the α,β-unsaturated bicyclic lactam 2 derived from (S)-pyroglutaminol.     

Thio-analogues of 2-(1H-Heteroarylidene)-1H-indene-1,3(2H)-diones,synthesis and formation of metal complexes

2-(1H-Heteroarylidene)-1H-indene-1,3(2H)-diones were converted into anils and dianils and then into monothio- and dithio-derivatives by treatment with hydrogen sulphide. The 2-pyridinyl monothioderivate was converted into S-alkyl ethers. In contrast with the dione1 the thio-derivatives readily formed isolable complexes with transition metals. Spectroscopic and magnetic data are reported.

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Thio-Analoge von 2-(1H-Heteroaryliden)-1H-inden-1,3(2H)-dionen. Synthese und Bildung von Metallkomplexen

Zusammenfassung 2-(1H-Heteroaryliden)-1H-inden-1,3(2 H)-dione wurden in Anile und Dianile und durch anschließende Behandlung mit Schwefelwasserstoff in die entsprechenden Mono- und Di-thio-derivate umgewandelt. Aus den 2-Pyridinyl-monothio-derivaten wurdenS-Alkyl-ether erhalten. Im Gegensatz zum Dion1 bildeten die Thioderivate glatt isolierbare Komplexe mit Übergangsmetallen. Spektroskopische und magnetische Daten werden mitgeteilt.

     

Stereoselective synthesis of the nonproteinogenic amino acid (2S,3R)-3-amino-2-hydroxydecanoic acid from (4S,5S)-4-formyl-5-vinyl-2-oxazolidinone

(4S,5S)-4-Formyl-5-vinyl-2-oxazolidinone (4b), which is readily obtained via a zinc-silver-mediated reductive elimination of alpha-d-lyxofuranosyl phenyl sulfone (3b), is successfully converted to the naturally occurring, nonproteinogenic amino acid (2S,3R)-3-amino-2-hydroxydecanoic acid (2). Also in this study, a facile "oxazolidinone rearrangement" reaction is uncovered during the attempted formation of the (methylthio)thiocarbonate derivative of the oxazolidinone alcohol 7.     

Synthesis of 2-oxazolidinones from (1S,2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol

A series of isomeric 2-oxazolidinones has been synthesized from (1S, 2S)-2-amino-1-(4-nitrophenyl)-1,3-propanediol. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 579–584, April, 2006.     

Stereoselective synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidine from d-mannitol

A novel stereoselective synthesis of N-Boc-(2S,3S)-3-hydroxy-2-phenylpiperidine was achieved from d-mannitol involving the highly stereoselective addition of phenyl Grignard to an allyl imine (de >98%) and ring-closing metathesis (RCM) in the key steps.     

Organic base-catalyzed stereodivergent synthesis of (R)- and (S)-3-amino-4,4,4-trifluorobutanoic acids

Organic base-catalyzed reaction of (S)-N-tert-butanesulfinyl (3,3,3)-trifluoroacetaldimine with dialkyl malonates was found to be effective for synthesis of both (S,S(S)) and (R,S(S)) β-aminomalonates in high yield with good to excellent diastereoselectivity (76-98% de). The products of this Mannich reaction provide direct access to β-trifluoromethyl-β-alanine of either (R) or (S) absolute configuration.     

Stereoselective synthesis of (R)- and (S)-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acids, -carboxylates and -carboxamides

(R)-Monomethyl 2-methyl-2-(2-nitrophenoxy)malonates obtained by PLE catalyzed hydrolysis of the corresponding dimethyl malonates undergo solvent-dependent enantioselective cyclization to afford (R)-methyl 2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylates and (S)-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic acids, respectively. These compounds are easily converted to enantiomerically and diastereomerically pure carboxamides, which are used as peptidomimetic building blocks.     

Studies towards the synthesis of (1R,2S)- and (1S,2S)-1,2-epoxy-3-hydroxypropylphosphonates and (1S,2S)- and (1R,2S)-2,3-epoxy-1-hydroxypropylphosphonates

The trans-configured fosfomycin analogue, diethyl (1S,2S)-1,2-epoxy-3-hydroxypropylphosphonate, was synthesised by the intramolecular Williamson reaction of diethyl (1S,2R)-1,3-dihydroxy-2-mesyloxypropylphosphonate. The cis-analogue was obtained as O-ethyl or O,O-diethyl (1R,2S)-1,2-epoxy-3-hydroxypropylphosphonates, when (1R,2R)-1,3-dihydroxy-2-mesyloxypropylphosphonate or its 3-O-trityl derivative were used as starting materials, respectively. The intramolecular Williamson cyclisations of diethyl (1S,2R)- and (1R,2S)-1-benzyloxy-3-hydroxy-2-mesyloxypropylphosphonates led to diethyl (1S,2S)- and (1R,2S)-2,3-epoxy-1-benzyloxypropylphosphonates, respectively, with the concomitant formation of diethyl (E)-1-benzyloxy-3-hydroxyprop-1-en-1-phosphonate. From diethyl (1S,2S)- and (1R,2S)-2,3-epoxy-1-benzyloxypropylphosphonates, enantiomerically pure diethyl (1S,2S)- and (1R,2S)-1,2-dihydroxypropylphosphonates were obtained by catalytic hydrogenation, while diethyl (1S,2S)- and (1R,2S)-3-acetamido-1,2-dihydroxypropylphosphonates were produced after epoxide ring opening with dibenzylamine, acetylation and hydrogenolysis.     

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.     

Chlorodiphenyltin(IV) and triphenyltin(IV) complexes of N-alkylated 2-amino-1-cyclopentene-1-carbodithioic acids: synthesis, spectroscopic characterization and X-ray studies

Four new complexes, [Ph₃Sn(isopropylACDA)] (1), [Ph₂SnCl(isopropylACDA)] (2), [Ph₃Sn(secbutylACDA)] (3), and [Ph₂SnCl(secbutylACDA)] (4), have been prepared from reaction between N-alkylated 2-amino-1-cyclopentene-1-carbodithioic acids (ACDA) with Ph₂SnCl₂ and Ph₃SnCl in 1:1 ratio. All complexes are characterized by FTIR, multinuclear NMR (¹H, ¹³C, and ¹¹⁹Sn) and mass spectrometry. In all complexes, the S–H proton has been removed and coordination takes place through the carbodithioate moiety. The ¹¹⁹Sn NMR data are consistent with five coordination of tin atom in solution. Complexes 2, 3, and 4 have also been confirmed by single X-ray crystallography. All three crystals are triclinic with space group P − 1. In complexes 2 and 4, the geometry around tin atom is distorted trigonal bipyramidal while in 3 the geometry is in between distorted tetrahedral and trigonal bipyramid. In all three structures, ligands are asymmetrically coordinated to tin atom. In addition, crystal structures are further stabilized by N–H···S hydrogen bonding.     

Stereoselective synthesis of (1R,2R)-1-amino-2-hydroxycyclobutanecarboxylic acid—serine derivative—, from racemic or optically active 2-benzyloxycyclobutanone

An easy and efficient one-pot reaction from readily available 2-benzyloxycyclobutanone gave, by means of an asymmetric Strecker synthesis, a kinetic or thermodynamic nitrile with good selectivity. After separation, the major trans-amino nitrile underwent basic hydrolysis and hydrogenolysis, followed by acidic hydrolysis, to give optically active (1R,2R)-1-amino-2-hydroxycyclobutanecarboxylic acid, serine derivative. The absolute configuration has been established by X-ray analysis of the corresponding cis-amino nitrile.     

A new synthesis of (R)- and (S)-2-2H-amino acids,including (R)- and (S)-2-2H1-glycine via stereochemically inert Co(III) complexes

Chemical synthesis of deuterated optically active 2-²H-amino acids via chiral complexes [Co(3-X-Sal-(S)-2-¹H-aa)₂]Na, where X is H, Me; aa is valine, norvaline, tyrosine, methionine, alanine and glycine; Sal is salicylaldehyde, is described.The technique includes preparation of a mixture of XXX and Δ diastereomeric complexes of [Co(3-X-Sal-(S)-2-¹H-aa)₂]Na which are separated on Al₂O₃.Then under the action of NaOD in D₂O the 2-¹H of the amino acid moiety is exchanged by deuterium, the resulting mixture of deuterated diastereomers is again separated on Al₂O₃, and optically active 2-²H aa are isolated after electrochemical reduction of pure deuterated diasteroisomers. S and R-2-²H₁glycines are obtained by stereospecific ¹H-²H exchange of glycine moiety in XXX and Δ [Co(3-Mesal-gly)₂]Na.     

Stereoselective synthesis of (2S,7S)-7-(4-phenoxymethyl)-2-(1-N-hydroxyureidyl-3-butyn-4-yl)oxepane: a potential anti-asthmatic drug candidate

We have achieved a short, efficient stereoselective synthesis of 7-membered oxepane derivatives with potential against asthma. Highlights of our synthetic strategy are regioselective oxidation of a hydroxyl group and efficient ring closure of an open chain aldehyde to a 2-benzenesulfonyl oxepane derivative with PhSO₂H. Surprisingly the cis-isomer showed better activity than the trans-isomer.     

An efficient asymmetric synthesis of (3S)-3-amino-1-(4-cyanophenyl)-2-oxopyrrolidine hydrochloride salt

Reaction of 4-aminobenzonitrile with 2-bromo-4-chlorobutyryl bromide in the presence of sodium phosphate followed by treatment of the coupled product with sodium hydroxide followed by ammonium hydroxide in acetonitrile yielded the title compound as the racemic (R)-(−)-mandelic acid salt in an overall yield of 64%. The title compound was then obtained with an ee >96% and in 78% yield after a dynamic resolution of the racemic salt in IPA using a catalytic amount of salicylaldehyde followed by salt exchange.     

Tetrameric copper(II) halide compounds containing (R,S)- and (S)-1-amino-2-propanolate ions

Summary Compounds with the composition CuXL, in which X=Cl^– or Br^– and L=R,S-1-amino-2-propanol andS-1-amino-2-propanol, both with deprotonated hydroxy groups, are described. Magnetic measurements strongly suggest these compounds to have a tetrameric cubane-type structure with a Cu₄O₄ core. The racemic and optically-active compounds show a different magnetic behaviour, most likely originating from different cluster types for the isomers. The results of the i.r., f.i.r. and e.s.r. spectra are in good agreement with the proposed cluster types.     

Stereoselective synthesis of 3-(1-Hydroxyethyl)-2-azetidinonesfrom 3-hydroxybutyrates

Addition of dianions of 3-hydroxybutyrates to benzylideneaniline results in direct formation of $\text{trans}$$\text{S*}$-3-(l-hydroxyethyl)-1,4-diphenyl-2-azetidinone with 95% diastereoselectivity. Inversion of the configuration at Cα, gives the desired $\text{trans}$$\text{R*}$-2-azetidinone in high yield.