Solid‐state conformations of linear depsipeptide amides with an alternating sequence of α,α‐disubstituted α‐amino acid and α‐hydroxy acid

Depsipeptides and cyclodepsipeptides are analogues of the corresponding peptides in which one or more amide groups are replaced by ester functions. Reports of crystal structures of linear depsipeptides are rare. The crystal structures and conformational analyses of four depsipeptides with an alternating sequence of an α,α‐disubstituted α‐amino acid and an α‐hydroxy acid are reported. The molecules in the linear hexadepsipeptide amide in (S)‐Pms‐Acp‐(S)‐Pms‐Acp‐(S)‐Pms‐Acp‐NMe₂ acetonitrile solvate, C₄₇H₅₈N₄O₉·C₂H₃N, ( 3b ), as well as in the related linear tetradepsipeptide amide (S)‐Pms‐Aib‐(S)‐Pms‐Aib‐NMe₂, C₂₈H₃₇N₃O₆, ( 5a ), the diastereoisomeric mixture (S,R)‐Pms‐Acp‐(R,S)‐Pms‐Acp‐NMe₂/(R,S)‐Pms‐Acp‐(R,S)‐Pms‐Acp‐NMe₂ (1:1), C₃₂H₄₁N₃O₆, ( 5b ), and (R,S)‐Mns‐Acp‐(S,R)‐Mns‐Acp‐NMe₂, C₃₀H₃₇N₃O₆, ( 5c ) (Pms is phenyllactic acid, Acp is 1‐aminocyclopentanecarboxylic acid and Mns is mandelic acid), generally adopt a β‐turn conformation in the solid state, which is stabilized by intramolecular N—H…O hydrogen bonds. Whereas β‐turns of type I (or I′) are formed in the cases of ( 3b ), ( 5a ) and ( 5b ), which contain phenyllactic acid, the torsion angles for ( 5c ), which incorporates mandelic acid, indicate a β‐turn in between type I and type III. Intermolecular N—H…O and O—H…O hydrogen bonds link the molecules of ( 3a ) and ( 5b ) into extended chains, and those of ( 5a ) and ( 5c ) into two‐dimensional networks.     

α-Alkylation of Amino Acids without Racemization. Preparation of Either (S)- or (R)-α-Methyldopa from (S)-Alanine

Enantiomerically pure cis- and trans-5-alkyl-1-benzoyl-2-(tert-butyl)-3-methylimidazolidin-4-ones ( 1, 2, 11, 15, 16 ) and trans-2-(tert-butyl)-3-methyl-5-phenylimidazolidin-4-one ( 20 ), readily available from (S)-alanine, (S)-valine, (S)-methionine, and (R)-phenylglycine are deprotonated to chiral enolates (cf. 3, 4, 12, 21 ). Diastereoselective alkylation of these enolates to 5,5-dialkyl- or 5-alkyl-5-arylimidazolidinones ( 5, 6, 9, 10, 13a-d, 17, 18, 22 ) and hydrolysis give α-alkyl-α-amino acids such as (R)- and (S)-α-methyldopa ( 7 and 8a , resp.), (S)-α-methylvaline ( 14 ), and (R)-α-methyl-methionine ( 19 ). The configuration of the products is proved by chemical correlation and by NOE ¹H-NMR measurements (see 23, 24 ). In the overall process, a simple, enantiomerically pure α-amino acid can be α-alkylated with retention or with inversion of configuration through pivaladehyde acetal derivatives. Since no chiral auxiliary is required, the process is coined ‘self-reproduction of a center of chirality’. The method is compared with other α-alkylations of amino acids occurring without racemization. The importance of enantiomerically pure, α-branched α-amino acids as synthetic intermediates and for the preparation of biologically active compounds is discussed.     

Total synthesis of 2-(β-D-ribofuranosyl)thiazole-4-carboxamide (Tiazofurin) and of precursors of ribo-C-nucleosides

(1R,2S,4R)-2-Cyano-7-oxabicyclo[2.2.1]hept-5-en-2-yl (1S′)-camphanate ( 5 ) was transformed into (?)-methyl 2,5-anhydro-3,4,6-O-tris[(tert-butyl)dimethylsilyl]-D -allonate ( 2 ), (+)-1,3-diphenyl-2-{2′,3′,5′-O-tris[(tert-butyl)dimethylsilyl]-β-D -ribofuranosyl}imidazolidine ( 3 ), and the benzamide 20 of 1-amino-2,5-anhydro-1-deoxy-3,4,6-O-tris-[((tert-butyl)dimethylsily)]-D -allitol. Compound 2 was converted efficiently into optically active tiazofurin ( 1 ).     

N-Heteroaralkyl substituted α-amidinium thiolsulfates

The syntheses of a number of N-substituted α-amidinium thiolsulfates, CH₂(S₂O₃^?)-C(=NH₂⁺)NH(CH₂)nR are described, where n was varied from 1 to 3 and R represents such heteroaryl groups as 2-furyl, 2-thienyl, 3-indolyl and 2-, 3- and 4-pyridyl. The preparation of S-(2-imidazolinemethyl)thiolsulfuric acid, as an example of an N, N'-disubstituted α-amidinium thiolsulfate, is also reported.     

Chirale Synthesebausteine durch Kolbe-Elektrolyse enantiomerenreiner β-Hydroxy-carbonsäurederivate. (R)- und (S)-Methyl-sowie (R)-Trifluormethyl-γ-butyrolactone und -δ-valerolactone

Chiral Building Blocks for Syntheses by Kolbe Electrolysis of Enantiomerically Pure β-Hydroxybutyric-Acid Derivatives. (R)- and (S)-Methyl-, and (R)-Trifluoromethyl-γ-butyrolactones, and -δ-valerolactones The coupling of chiral, non-racemic R* groups by Kolbe electrolysis of carboxylic acids R*COOH is used to prepare compounds with a 1.4- and 1.5-distance of the functional groups. The suitably protected β-hydroxycarboxylic acids (R)- or (S)-3-hydroxybutyric acid, (R)-4,4,4-trifluoro-3-hydroxybutyric acid (as acetates; see 1 – 6 ), and (S)-malic acid (as (2S,5S)-2-(tert-butyl)-5-oxo-1,3-dioxolan-4-acetic acid; see 7 ) are decarboxylatively dimerized or ‘codimerized’ with 2-methylpropanoic acid, with 4-(formylamino)butyric acid, and with monomethyl malonate and succinate. The products formed are derivatives of (R,R)-1,1,1,6,6,6-hexafluoro-2,5-hexanediol (see 8 ), of (R)-5,5,5-trifluoro-4-hydroxypentanoic acid (see 9,10 ), of (R)- and (S)-5-hydroxyhexanoic acid (see 11 ) and its trifluoro analogue (see 12, 13 ), of (S)-2-hydroxy- and (S,S)-2,5-dihydroxyadipic acid (see 23, 20 ), of (S)-2-hydroxy-4-methylpentanoic acid (‘OH-leucine’, see 21 ), and of (S)-2-hydroxy-6-aminohexanoic acid (‘OH-lysine’, see 22 ). Some of these products are further converted to CH₃- or CF₃-substituted γ- and δ-lactones of (R)- or (S)-configuration ( 14 , 16 – 19 ), or to an enantiomerically pure derivative of (R)-1-hydroxy-2-oxocyclopentane-1-carboxylic acid (see 24 ). Possible uses of these new chiral building blocks for the synthesis of natural products and their CF₃ analogues (brefeldin, sulcatol, zearalenone) are discussed. The olfactory properties of (R)- and (S)-δ-caprolactone ( 18 ) are compared with those of (R)-6,6,6-trifluoro-δ-caprolactone ( 19 ).     

Stereoconvergent synthesis of N-Boc-(2R,3S)-3-hydroxy-2-phenylpiperidine

The stereoconvergent synthesis of N-Boc-(2R,3S)-3-hydroxy-2-phenylpiperidine from (R)-1-(2-((tert-butyldimethylsilyl)oxy)-1-phenylethyl)piperidin-2-one is described. The key steps involved are α-hydroxylation of quiral lactam with O₂, stereoconvergent reduction of (R)- or (S)-3-(benzyloxy)-piperidin-2-one with Red-Al® which afforded in both cases the trans-bicyclic oxazolidine in high stereoselectivity after chromatographic purification and a stereospecific Grignard addition to chiral bicyclic oxazolidine.     

Brominations of Cyclic Acetals from α-Amino Acids and α- or β-Hydroxy Acids with N-Bromosucinimide

The preparation of novel electrophilic building blocks for the synthesis of enantiomerically pure compounds (EPC) is described. Thus, the 2-(tert-butyl)dioxolanones, -oxazolidinones, -imidazolidinones, and -dioxanones obtained by acetalization of pivalaldehyde with 2-hydroxy-, 3-hydroxy-, or 2-amino-carboxylic acids are treated with N-bromosuccinimide under typical radical-chain reaction conditions (azoisobuytyronitril/CCl₄/reflux). Products of bromination in the α-position of the carbonyl group of the five-membered-ring acetals are isolated or identified ( 2, 5 , and 8 ; Scheme 1). The dioxanones are converted to 2H, 4H-dioxinones under these conditions ( 12 , 14 , 15 , 21 , and 22 ; Schemes 2 and 3). The products can be converted to chiral derivatives of pyruvic acid (methylidene derivatives 3 and 6 ) or of 3-oxo-butanoic and -pentanoic acid ( 16 and 23 ). The mechanism of the brominations is interpreted. The conversion of serine to enactiomcrically pure dioxanones 26–28 (Scheme 4) is also discussed.     

Synthesis of 3,4‐Fused γ‐Lactone‐γ‐Lactam Bicyclic Moieties as Multifunctional Synthons for Bioactive Molecules

A short approach for the synthesis of 3,4‐fused γ‐lactone‐γ‐lactam bicyclic systems ( 1 ) in diastereomeric mixtures from chiral D ‐alanine methyl ester hydrochloride is described. The key step towards lactonisation is the reduction of the carbonyl ketone of the 5R‐configured 3,5‐dimethylpyrrolidine‐2,4‐dione diastereomers ( 8 ) via sodium borohydride in the presence of hydrochloric acid. With the presence of ethyl acetyl functionality at C3‐position, ester hydrolysis of 8 occurred concomitantly with keto reduction leading to lactonisation and eventually affording the anticipated (3S,4S,5R), (3R,4R,5R), (3R,4S,5R) and (3S,4R,5R) bicyclic moieties. The formation of the fused systems was confirmed by mass spectroscopy (MS) and nuclear magnetic resonance (NMR) analyses.     

Enantioselektive Synthese von α-Phosphinoketonen. Vorläufige Mitteilung

Enantioselective Synthesis of α-Phosphinoketones The first asymmetric (C? P)-connective synthesis of α-phosphinoketones in high enantiomeric purity (e.e.91–97%) is described. Key step is the highly diastereoselective phosphinylation of SAMP-hydrazones (S)- 2 to produce α-phosphinohydrazones (S,R)- 3 , isolated as the more stable borane adducts. Subsequent ozonolysis afforded the title compounds (R)- 4 , potential ligands for enantioselective homogeneous catalysis.     

Two isomorphous ZnII/CoII complexes with tri‐tert‐butoxysilanethiol and histamine,and (4‐hydroxymethyl‐1H‐imidazole‐κN)bis(tri‐tert‐butoxysilanethiolato‐κ2O,S)zinc(II)

The complexes [2‐(1H‐imidazol‐4‐yl‐κN³)ethylamine‐κN]bis(tri‐tert‐butoxysilanethiolato‐κS)cobalt(II), [Co(C₁₂H₂₇O₃SSi)₂(C₅H₉N₃)], and [2‐(1H‐imidazol‐4‐yl‐κN³)ethylamine‐κN]bis(tri‐tert‐butoxysilanethiolato‐κS)zinc(II), [Zn(C₁₂H₂₇O₃SSi)₂(C₅H₉N₃)], are isomorphous. The central Zn^II/Co^II ions are surrounded by two S atoms from the tri‐tert‐butoxysilanethiolate ligand and by two N atoms from the chelating histamine ligand in a distorted tetrahedral geometry, with two intramolecular N—H...O hydrogen‐bonding interactions between the histamine NH₂ groups and tert‐butoxy O atoms. Molecules of the complexes are joined into dimers via two intermolecular bifurcated N—H...(S,O) hydrogen bonds. The Zn^II atom in [(1H‐imidazol‐4‐yl‐κN³)methanol]bis(tri‐tert‐butoxysilanethiolato‐κ²O,S)zinc(II), [Zn(C₁₂H₂₇O₃SSi)₂(C₄H₆N₂O)], is five‐coordinated by two O and two S atoms from the O,S‐chelating silanethiolate ligand and by one N atom from (1H‐imidazol‐4‐yl)methanol; the hydroxy group forms an intramolecular hydrogen bond with sulfur. Molecules of this complex pack as zigzag chains linked by N—H...O hydrogen bonds. These structures provide reference details for cysteine‐ and histidine‐ligated metal centers in proteins.     

Nucleophile Ringöffnung von α-Nitrocyclopropancarbonsäure-arylestern mit sterisch geschützter,aber elektronisch wirksamer Carbonyl- und Nitro-Gruppe. Ein neues Prinzip der α-Aminosäure-Synthese (2-Aminobutansäure-a4-Synthon)

Nucleophilic Ring Opening of Aryl α-Nitrocyclopropanecarboxylates with Sterically Protected but Electronically Effective Carbonyl and Nitro Group. A New Principle of α-Amino Acid Synthesis (2-Aminobutanoic Acid a⁴-Synthon) The readily available 2,4,6-tri(tert-butyl)-and 2,6-di(tert-butyl)-4-methoxypahenol esters 2 of α-nitrocyclo-propanecarboxaylic acid ring opening with C-, N-, O-, and S-nucleophiles (cyanide, malonate, azide, anilines, alkoxides, phenoxides, thiolates) in DMF or alcohol solvents (80–95% yield). The products 6 – 14 are 2-nitrobutanoates with the newly introduced substituent in the 4-position. Reduction of the NO₂ group with Zn/AcOH/Ac₂O gives N-acetyl-α-amino acid esters 16 – 22 (40–90% yield). Subsequent oxidative cleavage (H₂O₂/HCOOH) of The p-methoxy-phenyl esters 18 and 20 produces free amino acids (65% 23 and 67% 24 , respectively). Thus, the nitro ester 2 corresponds to a 2-aminobutanoic-acid a⁴-synthon, it is a ‘homo-Michael acceptor’ producing γ-substituted α-amino acids.     

Racemic and chiral 1‐[N‐(chloro­acetyl)carbamoylamino]‐2,3‐dihydro‐1H‐inden‐2‐yl chloroacetate

In the racemic crystals of (1S,2R)‐ or (1R,2S)‐1‐[N‐(chloro­acetyl)­carbamoyl­amino]‐2,3‐di­hydro‐1H‐inden‐2‐yl chloro­acetate, C₁₄H₁₄Cl₂N₂O₄, (I), the enantiomeric mol­ecules form a dimeric structure via the N—H?O cyclic hydrogen bond of the carbamoyl moieties. In the chiral crystals of (—)‐(1S,2R)‐1‐[N‐(chloro­acetyl)­carbamoyl­amino]‐2,3‐di­hydro‐1H‐inden‐2‐yl chloro­acetate, C₁₄H₁₄Cl₂N₂O₄, (II), the N—­H?O intermolecular hydrogen bond forms a zigzag chain around the twofold screw axis. The melting points and calculated densities of (I) and (II) are 446 and 396 K, and 1.481 and 1.445 Mg m^?3, respectively.     

A pair of diastereomeric 1:1 salts of (S)‐ and (R)‐2‐methylpiperazine with (2S,3S)‐tartaric acid

The structures of diastereomeric pairs consisting of (S)‐ and (R)‐2‐methylpiperazine with (2S,3S)‐tartaric acid are both 1:1 salts, namely (S)‐2‐methylpiperazinium (2S,3S)‐tartrate dihydrate, C₅H₁₄N₂²⁺·C₄H₄O₆²⁻·2H₂O, (I), and (R)‐2‐methylpiperazinium (2S,3S)‐tartrate dihydrate, C₅H₁₄N₂²⁺·C₄H₄O₆²⁻·2H₂O, (II), which reveal the formation of well defined ammonium carboxylate salts linked via strong intermolecular hydrogen bonds. Unlike the situation in the more soluble salt (II), the alternating columns of tartrate and ammonium ions of the less soluble salt (I) are packed neatly in a grid around the a axis, which incorporates water molecules at regular intervals. The increased efficiency of packing for (I) is evident in its lower `packing coefficient', and the hydrogen‐bond contribution is stronger in the more soluble salt (II).     

Highly diastereoselective synthesis of α-trifluoromethylated α-propargylamines by acetylide addition to chiral CF3-substituted N-tert-butanesulfinyl ketimines

A convenient and practical method for the preparation of enantiomerically pure α-trifluoromethylated α-propargylamines is described. A range of enantiopure α-trifluoromethylated α-propargyl sulfinamides were obtained by the addition of lithium acetylides generated in situ with n-BuLi and terminal alkynes to diverse chiral CF₃-substituted (S)-N-tert-butanesulfinyl ketimines in moderate to excellent yields (56–97%) and with uniformly excellent diastereoselectivities (>99:1) by using Ti(OⁱPr)₄ as the catalyst and THF as the polar solvent. Enantiomerically pure α-trifluoromethylated α,α-dibranched propargyl amines were then readily obtained in excellent yields (87–97%) by acidic cleavage of the tert-butanesulfinyl group.     

Synthesis and N-Methyl-D-aspartate (NMDA) Antagonist Properties of the Enantiomers of α-Amino-5-(phosphonomethyl)[1,1′-biphenyl]-3-propanoic Acid. Use of a New Chiral Glycine Derivative

The enantiomers of the title compound, 7a and ent- 7a , and of substituted analogues are synthesized. The absolute configuration of 7a is deduced from that of (tert-butyl 2-tert-butyl)-3-methyl-4-oxoimidazolidin-1-carboxylate ( 15 ) and from the trans-configuration of the intermediate 17a which in turn is assigned on the basis of ¹H-NMR nuclear Overhauser effect (NOE) measurements. Instead of 15 , the 2-isopropyl-substituted analogue 21 can also be employed. Its preparation from glycine, methylamine, isobutyraldehyde, and (Boc)₂O, and the resolution through the bis-O,O′-(4-toluyl)tartrate salt 20 are described. In two functional tests (rat neocortical slice and frog hemisected spinal cord preparation) the (S)-enantiomer 7a (SDZ EAB 515) is shown to be a very potent, selective competitive NMDA antagonist.     

Syntheses of the Enantiomers of γ-Cyclogeranic Acid, γ-Cyclocitral,and γ-Damascone: Enantioselective protonation of enolates

(R)-and (S)-γ-cyclogeranic acid ((R)-and (S)- 9 , resp.) were obtained by resolution of the racemate, and their absolute configurations determined by chemical correlation. The γ-acids (R)-and (S)- 9 were converted into (R)-and (S)-methyl γ-cyclogeranate ((R)-and (S)- 6 , resp.), and (R)-and (S)-γ-damascone ((R)-and (S)- 5 , resp.). A more direct entry to (R)-and (S)- 9 consisted in the enantioselective protonation of a thiol ester enolate with (?)- or (γ)-N-isopropylephedrine((?)- or (γ)- 20 ) and subsequent hydrolysis of the (R)-and (S)-S-phenyl γ-thiocyclogeranate ((R)- and (S)- 24 , resp.; 97% ee). The esters (R)- and (S)- 24 were also used as precursors of (R)- and (S)-γ-damascone ((R)- and (S)- 5 , resp.). Alternatively, (S)- 5 (75% ee) was obtained by enantioselective protonation of ketone enolate 29 with (?)-N-isopropylephedrine ((?)- 20 ). Organoleptic evaluation demonstrated that the (S)-enantiomers of methyl γ-cyclogeranate and γ-damascone are markedly superior to their (R)-enantiomers.     

Induced Folding of Protein‐Sized Foldameric β‐Sandwich Models with Core β‐Amino Acid Residues

The mimicry of protein‐sized β‐sheet structures with unnatural peptidic sequences (foldamers) is a considerable challenge. In this work, the de novo designed betabellin‐14 β‐sheet has been used as a template, and α→β residue mutations were carried out in the hydrophobic core (positions 12 and 19). β‐Residues with diverse structural properties were utilized: Homologous β³‐amino acids, (1R,2S)‐2‐aminocyclopentanecarboxylic acid (ACPC), (1R,2S)‐2‐aminocyclohexanecarboxylic acid (ACHC), (1R,2S)‐2‐aminocyclohex‐3‐enecarboxylic acid (ACEC), and (1S,2S,3R,5S)‐2‐amino‐6,6‐dimethylbicyclo[3.1.1]heptane‐3‐carboxylic acid (ABHC). Six α/β‐peptidic chains were constructed in both monomeric and disulfide‐linked dimeric forms. Structural studies based on circular dichroism spectroscopy, the analysis of NMR chemical shifts, and molecular dynamics simulations revealed that dimerization induced β‐sheet formation in the 64‐residue foldameric systems. Core replacement with (1R,2S)‐ACHC was found to be unique among the β‐amino acid building blocks studied because it was simultaneously able to maintain the interstrand hydrogen‐bonding network and to fit sterically into the hydrophobic interior of the β‐sandwich. The novel β‐sandwich model containing 25 % unnatural building blocks afforded protein‐like thermal denaturation behavior.     

Synthese von diastereo- und enantio-selektiv deuterierten β,ε-, β,β-, β,γ- und γ,γ-Carotinen

Synthesis of Diastereo- and Enantioselectively Deuterated β,ε-, β,β-, β,γ- and γ,γ-Carotenes We describe the synthesis of (1′R, 6′S)-[16′, 16′, 16′-²H₃]-β, εcarotene, (1R, 1′R)-[16, 16, 16, 16′, 16′, 16′-²H₆]-β, β-carotene, (1′R, 6′S)-[16′, 16′, 16′-²H₃]-γ, γ-carotene and (1R, 1′R, 6S, 6′S)-[16, 16, 16, 16′, 16′, 16′-²H₆]-γ, γ-carotene by a multistep degradation of (4R, 5S, 10S)-[18, 18, 18-²H₃]-didehydroabietane to optically active deuterated β-, ε- and γ-C₁₁-endgroups and subsequent building up according to schemes \documentclass{article}\pagestyle{empty}\begin{document}${\rm C}_{11} \to {\rm C}_{14}^{C_{\mathop {26}\limits_ \to }} \to {\rm C}_{40} $\end{document} and C₁₁ → C₁₄; C₁₄+C₁₂+C₁₄→C₄₀. NMR.- and chiroptical data allow the identification of the geminal methyl groups in all these compounds. The optical activity of all-(E)-[²H₆]-β,β-carotene, which is solely due to the isotopically different substituent not directly attached to the chiral centres, is demonstrated by a significant CD.-effect at low temperature. Therefore, if an enzymatic cyclization of [17, 17, 17, 17′, 17′, 17′-²H₆]lycopine can be achieved, the steric course of the cyclization step would be derivable from NMR.- and CD.-spectra with very small samples of the isolated cyclic carotenes. A general scheme for the possible course of the cyclization steps is presented.     

Metabolism of Deuterated Isomeric 6,7‐Dihydroxydodecanoic Acids in Saccharomyces cerevisiae – Diastereo‐ and Enantioselective Formation and Characterization of 5‐Hydroxydecano‐4‐lactone (=4,5‐Dihydro‐5‐(1‐hydroxyhexyl)furan‐2(3H)‐one) Isomers

The chemical synthesis of deuterated isomeric 6,7‐dihydroxydodecanoic acid methyl esters 1 and the subsequent metabolism of esters 1 and the corresponding acids 1a in liquid cultures of the yeast Saccharomyces cerevisiae was investigated. Incubation experiments with (6R,7R)‐ or (6S,7S)‐6,7‐dihydroxy(6,7‐²H₂)dodecanoic acid methyl ester ((6R,7R)‐ or (6S,7S)‐(6,7‐²H₂)‐ 1 , resp.) and (±)‐threo‐ or (±)‐erythro‐6,7‐dihydroxy(6,7‐²H₂)dodecanoic acid ((±)‐threo‐ or (±)‐erythro‐(6,7‐²H₂)‐ 1a , resp.) elucidated their metabolic pathway in yeast (Tables 1–3). The main products were isomeric ²H‐labeled 5‐hydroxydecano‐4‐lactones 2 . The absolute configuration of the four isomeric lactones 2 was assigned by chemical synthesis via Sharpless asymmetric dihydroxylation and chiral gas chromatography (Lipodex ^® E). The enantiomers of threo‐ 2 were separated without derivatization on Lipodex ^® E; in contrast, the enantiomers of erythro‐ 2 could be separated only after transformation to their 5‐O‐(trifluoroacetyl) derivatives. Biotransformation of the methyl ester (6R,7R)‐(6,7‐²H₂)‐ 1 led to (4R,5R)‐ and (4S,5R)‐(2,5‐²H₂)‐ 2 (ratio ca. 4 : 1; Table 2). Estimation of the label content and position of (4S,5R)‐(2,5‐²H₂)‐ 2 showed 95% label at C(5), 68% label at C(2), and no ²H at C(4) (Table 2). Therefore, oxidation and subsequent reduction with inversion at C(4) of 4,5‐dihydroxydecanoic acid and transfer of ²H from C(4) to C(2) is postulated. The 5‐hydroxydecano‐4‐lactones 2 are of biochemical importance: during the fermentation of Streptomyces griseus, (4S,5R)‐ 2 , known as L‐factor, occurs temporarily before the antibiotic production, and (?)‐muricatacin (=(4R,5R)‐5‐hydroxy‐heptadecano‐4‐lactone), a homologue of (4R,5R)‐ 2 , is an anticancer agent.     

Absolute Konfiguration von α-Doradexanthin und von Fritschiellaxanthin,einem neuen Carotinoid aus Fritschiella tuberosa IYENG

Absolute Configuration of α-Doradexanthin and of Fritschiellaxanthin, a New Carotenoid from Fritschiella tuberosa IYENG . Fritschiellaxanthin, a new oxocarotenoid produced by the green alga Fritschiella tuberosa, in a nitrogen-deficient medium is now shown to be (3 S, 3′ R, 6′ R)-3, 3′-dihydroxy-β, ?-caroten-4-one ( 4b ). It is not identical with α-Doradexanthin ( 5b ) previously found in goldfish (Carassius auratus) and to which we assign the (3 S, 3′ S, 6′ R)-chirality. Consequently, fritschiellaxanthin and α-Doradexanthin are C(3′)-epimers of lutein-4-on. Furthermore, the so-called ′lutein′ from goldfish has now been found to be identical with 3′-epilutein (3) . Therefore, fritschiellaxanthin is probably biogenetically derived from lutein (2) , whereas α-Doradexanthin is formed from 3′-epilutein (3) with 3, O-didehydrolutein (=(3R, 6′R)-3-hydroxy-β, ?-caroten-3′-one 10) as a precursor. For comparison, optically active 10 and 3 have been prepared from lutein (2) and are fully characterised.