Chemie von a-Aminonitrilen. Aldomerisierung von Glycolaldehyd-phosphat zu racemischen Hexose-2,4,6-triphosphaten und (in Gegenwart von Formaldehyd) racemischen Pentose-2,4-diphosphaten: rac-Allose-2,4,6-triphosphat und rac-Ribose-2,4-diphosphat sind die Reaktionshauptprodukte

Chemistry of α-Aminonitriles. Aldomerisation of Glycolaldehyde Phosphate to rac-Hexose 2,4,6-Triphosphates and (in Presence of Formaldehyde) rac-Pentose 2,4-Diphosphates: rac-Allose 2,4,6-Triphosphate and rac-Ribose 2,4-Diphosphate Are the Main Reaction Products Glyclaldehyde phosphate aldomerizes in aqueous NaOH solution to a product mixture containing the racemates of the two diastereoisomeric tetrose 2,4-diphosphates and eight hexose 2,4,6-triphosphates. At room temperature in the absence of air and after 7 days, a solution 0.08M in glycolaldehyde phosphate (=formylmethyl dihydrogenphosphate)and 2M in NaOH gives products, in up to 80% yield, with a tetrose/hexose derivative ratio of ca 1:10 and with rac-allose, 2,4,6-triphosphate comprising up to 50% of the mixture of sugar phosphates. When the reaction is run under the same conditions but in the presence of 0.5 mol-equiv. of formaldehyde, sugar phosphates are formed in up to 45% yield, with pentose 2,4-diphosphates now predominating over hexose triphosphates by a ration f 3:1 rac-Ribose 2,4-diphosphate is found to be the major component, the ratios am ribose, arabinose, lyxose, and xylose 2,4-diphosphates being 52:14:23:11 in a representative experiment. The pentose diphosphates are constitutionally stable under the reaction conditions (observed for 23 weeks), but the diastereoisomeric ratios slowly change with time (tc 22:34:30:14 after 23 weeks), showing that ribose 2,4-diphosphate is not the thermodynamically favored diastereoisomer. The observed product distributions in both the pentose and the hexose series (after 1 week) reveal an aldolization mode that is preferentially erythro in the product-determining step (the reaction of glycolaldehyde phosphate as its enolate with glycerinaldehyde 2-phosphate and tetrose 2,4-diphosphate, respectively). An attempt is made to rationalize both this fact and the kinetic predominance of ribose 2,4-diphosphate in the pentose series and allose 2,4,6-triphosphate in the hexose series. Their configuration along the C-chain can be interpreted as corresponding to a minimum number of 1-5 repulsions in the packing of phosphate and OH substituents and minimal steric interaction between substituents at the reaction centers in the transition state of the product-determining step. The aldomerization of glycolaldehyde phosphate in the presence of formaldehyde is a variant of the formose reaction, It avoids the formation of complex formose product mixtures, largely as a consequence of the fact that aldoses which are phosphorylated at the C(2)     

Chemie von α-Aminonitrilen. Aziridin-2-carbonitril,ein Vorläufer von rca-O3-Phosphoserinnitril und Glycolaldehyd-phosphat

Chemistry of α-Aminonitriles. Aziridine-2-carbonitrile, a Source of Racemic O′-Phosphoserinenitrile and Glycolaldehyde Phosphate Racemic aziridine-2-carbonitrile (rac- 1 ) in MeCN solution reacts regioselectively (> 90%) with 2 equiv. of T_sOH at room temperature to form the hydrotosylate of racemic O3-tosylserinenitrile (rac- 2 ) via β-ring opening (Scheme 2). A similar regioselective reaction takes place between rac-l and H₃PO₄ to produce racemic O₃-phosphoserinenitrite (rac-3) which is in turn a source of glycolaldehyde phosphate (=formylmethyl dihydrogenphosphate) under the conditions of a ‘retro-Strecker’ reaction in aqueous solution (Scheme 6). These experiments document a close structural relationship between the simplest of the sugar phosphates and an α-aminonitrile precursor. The English Footnotes (*) referring to Schemes 1-7 are intended to provide an extension of this summary.     

Warum Pentose- und nicht Hexose-Nucleinsäuren?? Teil I. Einleitung und Problemstellung,Konformationsanalyse für Oligonucleotid-Ketten aus 2′,3′-Dideoxyglucopyranosyl-Bausteinen (‘Homo-DNS’) sowie Betrachtungen zur Konformation von A- und B-DNS

Why Pentose and Not Hexose Nucleic Acids? Part I . Introduction to the Problem, Conformational Analysis of Oligonucleotide Single Strands Containing 2′,3′-Dideoxyglucopyranosyl Building Blocks (‘Homo-DNA’), and Reflections on the Conformation of A- and B-DNA Summary in collaboration with Prof. Dr. C.E. Wintner, Haverford College, Haverford, PA 19041-1392; academic guest, ETH, March and June/July, 1991. Chemical rationalization of the structure of a biomolecule can be sought through consideration of two criteria: first, the relationship between the structure and its biological function; and second, the structure's potential for constitutional self assembly. The latter criterion convers the judgment, by chemical reasoning, of the chance of its preformation, that is, a synthetic event which must have been undergone by any molecular structure in order to have been selected (or to have selected itself) to become a biomolecule. One way to further the task of rationalizing a biomolecule's structure by experimental means is the design, synthesis, and study of structural alternatives which might have become biomolecules on the basis of either criterion, but which do not, in fact, appear in Nature today. In the formation of sugar phosphates from glycolaldehyde phosphate under basic conditions, straightforward and selective formation of rac-hexose 2,4,6-triphosphates is observed in the absence of formaldehyde, while rac-pentose 2,4-diphosphates are dominant, when (0.5 equiv.) formaldehyde is present [1]. This and other observations indicate that hexose sugars should be regarded to have had a chance of preformation comparable with that of pentose sugars. Why, then, did Nature choose pentoses and not hexoses as the sugar building blocks of nucleic acids? The reason must be functional; it must be the case that pentose nucleic acids are biologically superior to potential hexose alternatives. To the extent that biological function is a consequence of molecular structure and reactivity, the origin of this superiority should be decipherable through chemical experiment, that is, through synthesis of hexose nucleic acids, systematic study of their chemical properties, and comparison of these properties with those of their natural counterparts. This has been the object of the present investigation, initiated in 1986. The paper introduces a series of papers which will describe the results of a model study, namely, the synthesis, pairing properties and structure of homo-DNA oligonucleotides.     

Synthese von optisch aktiven,natürlichen Carotinoiden und strukturell verwandten Naturprodukten. VIII. Synthese von (3S,3′S)-7,8,7′,8′-Tetradehydroastaxanthin und (3S,3′S)-7,8-Didehydroastaxanthin (Asterinsäure)

Synthesis of Optically Active Natural Carotenoids and Structurally Related Compounds. VIII. Synthesis of (3S,3′S)-7,8,7′,8′-Tetradehydroastaxanthin and (3S,3′S)-7,8-Didehydroastaxanthin (Asterinic Acid) The synthesis of all-trans-(3S,3′S)-3,3′-dihydroxy-7,8, 7′,8′-tetradehydro-β, β-carotene-4,4′-dione ( 1 ), of all-trans-(3S,3′S)-3,3′-dihydroxy-7, 8-didehydro-β,β-carotene-4,4′-dione ( 2 ) (asterinic acid = mixture of 1 and 2 ), and of their 9,9′-di-cis- and 9-cis-isomers is reported starting from (4′S)(2E)-5-(4′-hydroxy-2′, 6′,6′-trimethyl-3′-oxo-l′-cyclohexenyl)-3-methyl-2-penten-4-ynal ( 8 ). The absolute configuration (3S,3′S) for both components 1 and 2 of asterinic acid ex Asterias rubens is confirmed on the basis of spectroscopic and direct comparison.     

Oxydative Aryl-Aryl-Verknüpfung von 6,6′,7,7′-Tetramethoxy-1,1′,2,2′,3,3′,4,4′-octahydro-1,1′-biisochinolin-Derivaten

Oxidative Aryl-Aryl-Coupling of 6,6′,7,7′-Tetramethoxy-1,1′,2,2′,3,3′,4,4′-octahydro-1,1′-biisoquinoline Derivatives We describe the synthesis of 2 by intramolecular oxidative coupling of 1, 1′-biisoquinoline derivatives 1 (Scheme 1). This heterocyclic system can be considered as a union of two apomorphine molecules and may thus exhibit dopaminergic activity. - The readily available tetrahydrobiisoquinoline 6 was methylated to 11 (Scheme 4) and reduced (with NaBH₃CN) to rac- 7 and (catalytically) to meso- 7 (Scheme 3). Reduction of 11 with NaBH₄ and of the biurethane rac- 9 with LiAlH₄/AlCl₃ afforded meso- and rac- 10 , respectively (Scheme 4). Demethylation of 6 , meso- 10 , meso- and rac- 7 led to 12 , meso- 14 , meso- and rac- 13 , respectively (Scheme 5). The latter two phenols were converted with chloroformic ester to the hexaethoxycarbonyl derivatives meso- and rac- 15 and subsequently saponified to the biurethanes meso- and rac- 16 , respectively (Scheme 5). - In order to assure proximity of the two aromatic rings, the ethano-bridged derivatives meso- and rac- 18 were prepared by condensing meso- and rac- 7 with oxalic ester and reducing the oxalyl derivatives meso- and rac- 17 with LiAlH₄/AlCl₃, respectively (Scheme 6). The ¹H-NMR, spectra at different temperatures showed that rac- 18 populated two conformers but rac- 17 only one, all with C₂-symmetry, and that meso- 17 as well as meso- 18 populated two enantiomeric conformers with C₁-symmetry. Whereas both oxalyl derivatives 17 were fairly rigid due to the two amide groupings, the ethano derivatives 18 exhibited coalescence temperatures of -20 and 30°. - The intramolecular coupling of the two aromatic rings was successful under ‘non-phenolic oxidative’ conditions with the tetramethoxy derivatives 7, 10 and 18 , the rac-isomers leading to the desired dibenzophenanthrolines, the meso-isomers, however, mostly to dienones (Scheme 9): With VOF₃ and FSO₃H in CF₃COOH/CH₂Cl₂ rac- 7 was converted to rac- 19 , rac- 18 to rac- 21 and rac- 10 to a mixture of rac- 20 and the dienone 23b of the morphinane type. Under the same conditions meso- 10 was transformed to the dienone 23a of the morphinane type, whereas meso- 18 yielded the dienone 24 of the neospirine type, both in lower yields. The analysis of the spectral data of the six coupling products offers evidence for their structures. With the demethylation of rac- 20 and rac- 21 to rac- 25 and rac- 26 , respectively, the synthetic goal of the work was reached, but only in the rac-series (Scheme 10). - In the course of this work two cleavages of octahydro-1,1′-biisoquinolines at the C(1), C(1′)-bond were observed: (1) The biurethanes 9 and 16 in both the meso- and rac-series reacted with oxygen in CF₃COOH solution to give the 3,4-dihydroisoquinolinium salts 27 and 28 ; the latter was deprotonated to the quinomethide 30 (Scheme 11). (2) Under the Clarke-Eschweiler reductive-methylation conditions meso- and rac- 7 were cleaved to the tetrahydroisoquinoline derivative 32 .     

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.     

Optisch aktive 4,5-Epoxy-4,5-dihydro-α-ionone und Synthese der stereoisomeren 4,5:4′,5′-Diepoxy-4,5,4′,5′-tetrahydro-ϵ,ϵ-carotine und der sterische Verlauf ihrer Hydrolyse

Optically Active 4,5-Epoxy-4,5-dihydro-α-ionones; Synthesis of the Stereoisomeric 4,5:4′,5′-Diepoxy-4,5,4′,5′-tetrahydro-?,?-carotenes and the Steric Course of their Hydrolysis We prove that epoxidation with peracid of α-ionone, contrary to a recently published statement, predominantly leads to the cis-epoxide. Acid hydrolysis affords a single 4,5-glycol whose structure, established by an X-ray analysis, shows that oxirane opening occurred with inversion at the least substituted position (C(4)). Stable cis-and trans-epoxides are prepared by epoxidation of the C₁₅-phosphonates derived from α-ionone. Both the racemic and optically active form are used for the synthesis of the 4,5:4′,5′-diepoxy-4,5,4′,5′-tetrahydro-?,?-carotenes having the following configuration in the end groups: meso-cis/cis, meso-trans/trans, rac-cis/trans, rac- and (6R, 6′ R)-cis/cis, rac- and (6R, 6′R)-trans/trans, rac- and (6R, 6′R)-cis/trans, and (6R, 6′ R)-cis/?. Acid hydrolysis of the cis/cis-epoxycarotenoids under relatively strong conditions occurs again with inversion at C(4)/C(4′) in case of the cis/cis-epoxycarotenoids, but at C(5)/C(5′) in case of the trans/trans-epoxycarotenoids. An independent synthesis of this 4,5,4′,5′-tetrahydro-?,?-carotene-4,5,4′,5′-tetrol is presented. The irregular results of the oxirane hydrolysis are explained by assumption of neighbouring effects of the lateral chain. 400-Mz-¹H-NMR data are given for each of the stereoisomeric sets. In the visible range of the CD spectra, the (6R, 6R′)-epoxycarotenoids compared with (6R, 6R′)-?,?-carotene exhibit an inversion of the Cotton effects.     

Synthesen von enantiomerenreinen Apoviolaxanthin-säuren, -olen und -alen (Persicaxanthin,Sinensiaxanthin und β-Citraurin-epoxid) und ihrer furanoiden Umlagerungsprodukte

Synthesis of Enantiomerically Pure Apoviolaxanthinoic Acids, Apoviolaxanthinols, and Apoviolaxanthinals (Including Persicaxanthin, Sinensiaxanthin, and β-Citraurin Epoxide) and of their Furanoid Rearrangement Products Starting from (1′S,2′R,4′S,2E,4E)-5-(1′,2′-epoxy-4′-hydroxy-2′,6′,6′-trimethylcyclohexy1)-3-methy1-2,4-pentadienal ( 3 ), a recently described synthon [6], a full range of C₂₀-, C₂₅-, C₂₇-, and C₃₀-polyenic acids, alcohols, and aldehydes and their (8R)- and (8S)-diastereoisomeric furanoid rearrangement products was prepared. The synthetic C₂₅-alcohols proved to be identical with persicaxanthin (= 12′-apoviolaxanthin-12′-ol) and perisicachromes (= 12′-apoauroxanthin-12′-ols) and the C₂₇-alcohols analogously with sinensiaxanthin and sinensiachromes. A correlation between the sign of the Cotton effects in the CD spectra of 5,6-and 5,8-epoxides and their configuration at C(6) and C(8), respectively, was established.     

Synthesis of symmetrical 2,2′,4,4′-tetrasubstituted[4,4′-bioxazole]-5,5′(4H,4′H)-diones and their reactions with some nucleophiles

Several symmetrical 2,2′,4,4′-tetrasubstituted[4,4′-bioxazole]-5,5′(4H,4′H)-diones 1a-f were obtained by dehydrodimerization of 5(4H)-oxazolones 2a-f . The configurations of four were established; one by X-ray crystallography rac- 1c , and three rac- 1a , meso- 1a and rac- 1b by ¹H nmr spectroscopy of their derivatives. Upon being heated, the bioxazolones isomerized, presumably by breakage of the 4,4′-carbon? carbon bond to form free radicals followed by their recombination. The results of a crossover experiment were consistent with a radical nature for this isomerization reaction. Treatment of three of the bioxazolones rac- 1a , meso- 1a and rac- 1c with methanol and amine nucleophiles led to ester and amide derivatives 7–11 of α,α'-dehydrodimeric amino acids.     

1,2-Epoxycarotinoide. 4. Mitteilung. Synthese, 1H-NMR- und CD-Studien von (S)-1,2-Epoxy-1,2-dihydrolycopin und (S)-1′,2′-Epoxy-1′,2′-dihydro-γ-carotin

1,2-Epoxycarotenoids: Synthesis, ¹H-NMR and CD Studies of (S)-1,2-Epoxy-1,2-dihydrolycopene and (S)-1′,2′-Epoxy-1′, 2′ -dihydro-γ-carotene The synthesis of (S)-1,2-epoxy-1,2-dihydrolycopene (^(S)- 1 ) and (S)-1′, 2′ -epoxy- 1′, 2′ -dihydro-γ-carotene ((S)- 2 ) are described. The CD spectra of the (all-E)-isomers and of the isomers (7Z, S)- 1 and (7′Z, S)- 2 are discussed. The comparison of the CD spectra of the synthetic (S)- 1 and the compound isolated from the tomatoes proves the (S)-configuration of the natural product.     

Synthese von Alkylphenolen und -pyrocatecholen aus Plectranthus albidus (Labiatae)

Synthesis of Alkylphenols and -catechols from Plectranthus albidus (Labiatae) In the preceding paper, we described the isolation and structure elucidation of a series of even-numbered phenol- or pyrocatechol-derived 1-arylalkane-5-ones. To establish the assigned structures unambiguously and to have larger quantities available for physiological testing, the following compounds were prepared: in the alkylphenol series, 1-(4′-hydroxyphenyl)tetradecan-5-one ( 2a ), 1-(4′-hydroxyphenyl)hexadecan-5-one ( 2b ), and 1-(4′-hydroxyphenyl)octadecan-5-one ( 2c ); in the alkylcatechol series, 1-(3′,4′-dihydroxyphenyl)decan-5-one ( 3a ; not isolated as a natural compound), 1-(3′,4′-dihydroxyphenyl)dodecan-5-one ( 3b ), 1-(3′,4′-dihydroxyphenyl)tetradecan-5-one ( 3c ), 1-(3′,4′-dihydroxyphenyl)hexadecan-5-one ( 3d ), 1-(3′,4′-dihydroxyphenyl)octadecan-5-one ( 3e ), and 1-(3′,4′-dihydroxyphenyl)icosan-5-one ( 3f ); in the alkenylphenol series, (Z)-1-(4′-hydroxyphenyl)octadec-13-en-5-one ( 4a ) and (E)-1-(4′-hydroxyphenyl)octadec-13-en-5-one ( 4b ); in the alkenylcatechol series, (E,E)-1-(3′,4′-dihydroxyphenyl)deca-1,3-dien-5-one ( 1 ) and (Z)-1-(3′,4′-dihydroxyphenyl)octadec-13-en-5-one ( 5 ). All compounds proved to be identical with the previously assigned structures. Compound 1 was synthesized by regioselective aldol condensation of heptan-2-one with (E)-1-(3′,4′-dimethoxyphenyl)prop-2-enal ( 6d ; Scheme 1), the phenols 2a–c and the catechols 3a–f by addition of the corresponding alkyl Grignard reagent to 5-(4′-methoxyphenyl)- or 5-(3′,4′-dimethoxyphenyl)pentanal ( 17c and 18c , resp.; Scheme 4), and the olefins 4a, 4b and 5 from 17c or 18c via the 9-O-silyl-protected 13-(4′-methoxyphenyl)- or 13-(3′,4′-dimethoxyphenyl)tridecanals ( 26 and 27 , resp.) and Wittig olefination as the key steps (Scheme 5).     

Synthesis of (all-E,2R,2′R)-oscillol

Optically active (all-E,2R,2′R)-oscillol (= (all-E,2R,2′R)-3,4,3′,4′-tetradehydro-1,2,1′,2′-tetrahydro-ψ,ψ-carotene-1,2,1′,2′-tetrol; 1 ) was synthesized according to the C₁₀ + C₂₀ + C₁₀ = C₄₀ strategy, applying the Wittig reaction to couple the synthons 4 and 6 . The chiral centre was introduced by a Sharpless dihydroxylation of 3-methylbut-2-enyl 4-nitrobenzoate ( 8 ).     

Synthesen von (1R)-cis-3-(2′,2′-Dihalovinyl)-2, 2-dimethylcyclopropan-carbonsäuren via Favorskii-Umlagerung von optisch aktiven Cyclobutanonen

Syntheses of (1R)-cis-3-(2′,2′-Dihalovinyl)-2,2-dimethylcyclopropane Carboxylic Acids via Favorskii-rearrangement of Optically Active Cyclobutanones The cis-cyclobutanones 7 are resolved by means of optically active amine salts of their sodium hydrogen sulfite adducts. The desired (1R)-cis-carboxylic acids 9 are obtained from the (+)-cis-cyclobutanones 7 via Favorskii-rearrangement and HX-elimination. The recycling of undesired (?)-cis-cyclobutanones 7 is carried out in good yield by their racemization, thus rendering the total synthesis 1 + 2 → 9 chirally economic.     

Different nucleobase orientations in two cyclic 2′,3′‐phosphates of purine ribonucleosides: Et3NH(2′,3′‐cAMP) and Et3NH(2′,3′‐cGMP)·H2O

The crystal structures of triethyl­ammonium adenosine cyclic 2′,3′‐phosphate {systematic name: triethyl­ammonium 4‐(6‐amino­purin‐9‐yl)‐6‐hydroxy­methyl‐2‐oxido‐2‐oxoperhydro­furano[3,4‐c][1,3,2]dioxaphosphole}, Et₃NH(2′,3′‐cAMP) or C₆H₁₆N⁺·C₁₀H₁₁N₅O₆P⁻, (I), and guanosine cyclic 2′,3′‐phosphate monohydrate {systematic name: triethyl­ammonium 6‐hydroxy­methyl‐2‐oxido‐2‐oxo‐4‐(6‐oxo‐1,6‐dihydro­purin‐9‐yl)perhydro­furano[3,4‐c][1,3,2]dioxaphosphole monohydrate}, [Et₃NH(2′,3′‐cGMP)]·H₂O or C₆H₁₆N⁺·C₁₀H₁₁N₅O₇P⁻·H₂O, (II), reveal different nucleobase orientations, viz. anti in (I) and syn in (II). These are stabilized by different inter‐ and intra­molecular hydrogen bonds. The structures also exhibit different ribose ring puckering [₄E in (I) and ³T₂ in (II)] and slightly different 1,3,2‐dioxaphospho­lane ring conformations, viz. envelope in (I) and puckered in (II). Infinite ribbons of 2′,3′‐cAMP⁻ and helical chains of 2′,3′‐cGMP⁻ ions, both formed by O—H⋯O, N—H⋯X and C—H⋯X (X = O or N) hydrogen‐bond contacts, characterize (I) and (II), respectively.     

Darstellung,Kristallstruktur und Eigenschaften des Kupfer(II)‐Indium(III)‐Orthophosphats Cu3In2[PO4]4

Contributions on Crystal Chemistry and Thermal Behaviour of Anhydrous Phosphates. XXIV. Preparation, Crystal Structure, and Properties of Copper(II) Indium(III) Orthophosphate Cu₃In₂[PO₄]₄ Crystals of Cu₃In₂[PO₄]₄ were grown by chemical vapour transport (temperature gradient 1273 K → 1173 K) using chlorine as transport agent. The mixed metal phosphate forms a new structure type (P2₁/c, Z = 2, a = 8.9067(6), b = 8.8271(5), c = 7.8815(5) Å, β = 108.393(5)°, 13 atoms in asymmetric unit, 2549 unique reflections with F_o > 4σ, 116 variables, R(F²) = 0.065). The crystal structure shows a hexagonal closest packing of [PO₄]^3– tetrahedra. Close‐packed layers parallel (1 0 –1) are stacked according to the sequence A, B, A′, B′, A. The octahedral interstices in this packing are completely occupied by two In³⁺, one (Cu1)²⁺ and a “dumb bell” (Cu2)₂⁴⁺. In the latter case four of the six phosphate groups that belong to this octahedral void act as bi‐dentate ligands, thus forming dimers [(Cu2)₂O₁₀] with d_Cu–Cu = 3.032 Å. Cu₃In₂[PO₄]₄ is paramagnetic (μ_eff = 1.89 μ_B, θ_P = –16.9 K). The infrared and UV/Vis reflectance spectra are reported. The observed d‐electron levels of the Cu²⁺ cations agree well with those obtained from angular overlap calculations.     

Bis(2,4,7‐tri­methyl­indenyl)­cobalt(II) and rac‐2,2′,4,4′,7,7′‐hexamethyl‐1,1′‐biindene

The crystal and molecular structures of bis(η⁵‐2,4,7‐tri­methyl­indenyl)­cobalt(II), [Co(C₁₂H₁₃)₂], (I), and rac‐2,2′,4,4′,7,7′‐hexamethyl‐1,1′‐biindene, C₂₄H₂₆, (II), are reported. In the crystal structure of (I), the Co atom lies on an inversion centre and the structure represents the first example of a bis(indenyl)cobalt complex exhibiting an eclipsed indenyl conformation. The (1R,1′R) and (1S,1′S) enantiomers of the three possible stereoisomers of (II), which form as by‐products in the synthesis of (I), cocrystallize in the monoclinic space group P2₁/c. In the unit cell of (II), alternating (1R,1′R) and (1S,1′S) enantiomers pack in non‐bonded rows along the a axis, with the planes of the indenyl groups parallel to each other and separated by 3.62 and 3.69 Å.     

Umlagerungsreaktionen von (2′-Propinyl)cyclohexadienolen und -semibenzolen

Rearrangements of (2′-Propinyl)cyclohexadienols and -semibenzenes The acid-catalyzed dienol-benzene rearrangement of 3- and 5-methyl-substituted (2′-propinyl)cyclohexadienols has been investigated. Treatment of the dienols with CF₃COOH in CCl₄ yields allenyl- and (2′-propinyl)benzenes via [3,4]- and [1,2]-sigmatropic rearrangements, respectively. The reaction with H₂SO₄ in Et₂O leeds to a mixture of allenyl-, 2′-propinyl-, 3′-butinyl- and (2′,3′-butadienyl)benzenes (Scheme 3). The latter are products of a thermal semibenzene-benzene rearrangement (cf. Scheme 9). The corresponding semibenzenes have been prepared by dehydration of the cyclohexadienols with H₂SO₄ or POCl₃ (Schemes 6 and 7). Under acidic conditions, the p-(2′-propinyl)semibenzenes 33–35 (Scheme 8) undergo [3,4]- and [1,2]-sigmatropic rearrangements to give again allenyl- and (2′-propinyl)benzenes, whereas the thermal rearrangements to the 3′-butinyl- and (2′,3′-butadienyl)benzenes (Scheme 9) involves a radical mechanism. In contrast, the o-(2′-propinyl)semibenzene b (Scheme 7) leads to (2′,3′-butadienyl)benzene 32 via a thermal [3,3]-sigmatropic rearrangement.     

Syntheses of 6,8-disubstituted-9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphates

A series of 6,8-disubstituted-9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphates were prepared employing preformed 9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphate precursors. Three synthetic approaches were utilized to accomplish the syntheses. The first approach involved a study of the order of nucleophilic substitution, 6 vs 8, of the intermediate 6,8-dichloro-9-β-D-ribofuranosyipurine 3′,5′-cyclic phosphates ( 2 ) with various nucleophilic agents to yield 8-amino-6-chloro-, 8-chloro-6-(diethylamino)-, 6-chloro-8-(diethylamino)-, 6,8-bis-(diethylamino)- and 8-(benzylthio)-6-chloro-9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphate (4, 9, 10, 11, 13) respectively and 6-chloro-9-β-D-ribofuranosylpurin-8-one 3′,5′-cyclic phosphate ( 5 ) and 8-amino-9-β-D-ribofuranosylpurine-6-thione 3′,5′-cyclic phosphate ( 6 ). The order of substitution was compared to similar substitutions on 6,8-dichloropurines and 6,8-dichloropurine nucleosides. The second scheme utilized nucleophilic substitution of 6-chloro-8-substituted-9-β-D-ribofuranosylpurine 3′,5′-cyclic, phosphates obtained from the corresponding 8-subslituted inosine 3′,5′-cyclic phosphates by phosphoryl chloride, 6,8-bis-(benzylthio)-, 6-(diethylamino)-8-(benzylthio),8-(p-chlorophenylthio(-6-(diethylamino)- and 6,8-bis-(methyl-thio)-9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphates ( 14, 12, 20 , and 21 ) respectively, were prepared in this manner. The final scheme involved N¹-alkylation of an 8-substituted adenosine 3′,5′-cyclic phosphate followed by a Dimroth rearrangement to give 6-(benzylamino)-8-(methylthio)- and 6-(benzylamino)-8-bromo-9-β-D-ribofuranosylpurine 3′,5′-cyclic phosphate ( 24 and 25 ).     

Synthese von enantiomerenreinem Mimulaxanthin und seiner (9Z,9′Z)- und (15Z)-Isomeren

Synthesis of Enantiomerically Pure Mimulaxanthin and of Its (9Z,9′Z)- and (15Z)Isomers We present the details of a synthesis of optically active, enantiomerically pure stereoisomers of mimulaxanthin (=(3s,5R,6R,3′S,5′R,6′R)-6,7,6′,7′-tetradehydro-5,6,5′,6′-tetrahydro-β,β-carotin-3,5,3′,5′-tetrol) either as free alcohols 1a and 24a or as their crystalline (t-Bu)Me₂Si ethers 1b and 24b . Grasshopper ketone 2a , a presumed synthon, unexpectedly showed a very sluggish reaction with Wittig-Horner reagents. Upon heating with the ylide of ester phosphonates, an addition across the allenic bond occurred. On the contrary, a slow but normal 1,2-addition took place with the ylide from (cyanomethyl)phosphonate but, unexpectedly, with concomitant inversion at the chiral axis. So a mixture of(6R,6S,9E,9Z)-isomers 6 – 9 was produced {(Scheme 1). However, a fast and very clean 1,2-addition occurred with the ethynyl ketone 12 to yield the esters 13 and 14 (Scheme 2). DIBAH reduction of the separated stereoisomers gave the allenic alcohols 15 and 16 in high yield. Mild oxidation to the aldehydes 17 and 18 followed by their condensation with the acetylenic C₁₀-bis-ylide 19 led to the stereoisomeric 15,15′-didehydromimulaxanthins 20 and 22 , respectively (Schemes 3 and 4). Mimulaxanthins 1 and 24 were prepared by partial hydrogenation of 20 and 22 followed by a thermal (Z/E)-isomerization. As expected, the mimulaxanthins exhibit very weak CD curves, obviously caused by the allenic bond that insulates the chiral centers in the end group from the chromophor. On the contrary, some of the C₁₅-allenic synthons showed not only fairly strong CD effects but also a split CD curve which, in our interpretation, results from an exciton coupling between the allene and the C(9)?C(10) bond. We postulate a rotation around the C(8)? C(9) bond, presumably caused by an intramolecular H-bond in 16 or by a dipol interaction between the polarized double bonds in 6 , 7 , 8 , and 17 .     

2′, 3′-Dideoxy-3′-fluorotubercidin and Related Dideoxyribonucleosides:. Synthesis via a 2′-deoxy-3′-oxoribofuranoside intermediate and conformation studies

An efficient synthesis of the unknown 2′-deoxy-D-threo-tubercidin ( 1b ) and 2′, 3′-dideoxy-3′-fluorotubercidin ( 2 ) as well as of the related nucleosides 9a, b and 10b is described. Reaction of 4-chloro-7-(2-deoxy-β-D-erythro-pentofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine ( 5 ) with (tert-butyl)diphenylsilyl chloride yielded 6 which gave the 3′-keto nucleoside 7 upon oxidation at C(3′). Stereoselective NaBH₄ reduction (→ 8 ) followed by deprotection with Bu₄NF(→ 9a )and nucleophilic displacement at C(6) afforded 1b as well as 7-deaza-2′-deoxy-D-threo-inosine ( 9b ). Mesylation of 4-chloro-7-{2-deoxy-5-O-[(tert-butyl)diphenylsilyl]-β-D-threo-pentofuranosyl}-7H-pyrrolo[2,3-d]-pyrimidine ( 8 ), treatment with Bu₄NF (→ 12a ) and 4-halogene displacement gave 2′, 3′-didehydro-2′, 3′-dideoxy-tubercidin ( 3 ) as well as 2′, 3′-didehydro-2′, 3′-dideoxy-7-deazainosne ( 12c ). On the other hand, 2′, 3′-dideoxy-3′-fluorotubercidin ( 2 ) resulted from 8 by treatment with diethylamino sulfurtrifluoride (→ 10a ), subsequent 5′-de-protection with Bu₄NF (→ 10b ), and Cl/NH₂ displacement. ¹H-NOE difference spectroscopy in combination with force-field calculations on the sugar-modified tubercidin derivatives 1b , 2 , and 3 revealed a transition of the sugar puckering from the ^3′T_2′ conformation for 1b via a planar furanose ring for 3 to the usual ^2′T_3′ conformation for 2.