Photochemische Cycloadditionen von 3-Phenyl-2H-azirinen mit Ketonen,Acylcyaniden und Ketoestern. 33. Mitteilung über Photoreaktionen

Similarly to aldehydes [6] ketones form 3-oxazolines via cyclo-addition to the benzonitrile-methylides 2 that arise photochemically from the 3-phenyl-2H-azirines 1 . With various ketones benzonitrile-isopropylide ( 2a ) gives cyclo-addition products in very good preparative yields (scheme 1). Benzonitrile-ethylide ( 2c ) and benzonitrile-benzylide ( 2b ) [8] react, however, sluggishly with ketones, smooth cyclo-addition being observed in their case only with «activated» ketones (2,2,2-trifluoro-acetophenone, 1,1,1-trifluoro-2-propanone). With 1a acetonyl-acetone forms the bis-adduct 12 While the azirine 1a reacts with cyclohexanone to yield essentially only the spiro-(3-oxazoline) 13 , it gives with cyclopentanone, depending on the reaction conditions, either the spiro-(3-oxazoline) 14 or the butenyl-3-oxazoline 15 (scheme 3). The formation of 15 has to be preceded by the photochemical formation of 4-pentenal from the ketone. Norcamphor and camphor react in a similar way (schemes 4 and 5). The azirines 1a–c react smoothly with the keto groups in acylcyanides and α-keto-esters, giving with the former 5-cyano-3-oxazolines and with the latter 5-ethoxycarbonyl-3-oxazolines (schemes 6 and 7). β-Keto-esters (acetoacetic ester) form with the dipole arising from 1a the expected addition product 31 and, via the protonated dipole d (scheme 8), finally the benzylidene-acetoacetic ester. Analogous results are obtained with malonodinitrile, trifluoro-acetamide and other weak acids such as alcohols [29] [30] (scheme 9). The light-induced rearrangement of the bicyclic isoxazoline 37 into the oxazoline 38 is visualized as an intramolecular cyclo-addition reaction (scheme 10). The cyclo-addition in this case proceeds with the aldehyde group inversed as compared to the related intermolecular benzonitrile–methylide addition to aldehydes.     

Untersuchungen über aromatische Amino-Claisen-Umlagerungen

Investigations on Aromatic Amino-Claisen Rearrangements The thermal and acid catalysed rearrangement of p-substituted N-(1′,1′-dimethylallyl)anilines (p-substituent=H (5) , CH₃ (6) , iso-C₃H₇ (7) , Cl (8) , OCH₃ (9) , CN (10) ), of N-(1′,1′-dimethylallyl)-2,6-dimethylaniline (11) , of o-substituted N-(1′-methylallyl)anilines (o-substituent=H (12) , CH₃ (13) , t-C₄H₉ (14) , of (E)- and (Z)-N-(2′-butenyl)aniline ((E)- and (Z)- 16 ), of N-(3′-methyl-2′-butenylaniline (17) and of N-allyl- (1) and N-allyl-N-methylaniline (15) was investigated (cf. Scheme 3). The thermal transformations were normally conducted in 3-methyl-2-butanol (MBO), the acid catalysed rearrangements in 2N -0,1N sulfuric acid. - Thermal rearrangements. The N-(1′,1′-dimethylallyl)anilines rearrange in MBO at 200-260° with the exception of the p-cyano compound 10 in a clean reaction to give the corresponding 2-(3′-methyl-2′-butenyl)anilines 22–26 (Table 2 and 3). The amount of splitting into the anilines is <4% ( 10 gives ? 40% splitting). The secondary kinetic deuterium isotope effect (SKIDI) of the rearrangement of 5 and its 2′,3′,3′-d₃-isomer 5 amounts to 0.89±0.09 at 260° (Table 4). This indicates that the partial formation of the new s?-bond C(2), C(3′) occurs already in the transition state, as is known from other established [3,3]-sigmatropic rearrangements. The rearrangement of the N-(1′-methylallyl)anilines 12–14 in MBO takes place at 290–310° to give (E)/(Z)-mixtures of the corresponding 2-(2′-Butenyl)anilines ((E)- and (Z)- 30,-31 , and -32 ) besides the parent anilines (5–23%). Since a dependence is observed between the (E)/(Z)-ratio and the bulkiness of the o-substituent (H: (E)- 30 /(Z)- 30 =4,9; t-C₄H₉: (E)- 32 /(Z)- 32 =35.5; cf. Table 6), it can be concluded, that the thermal amino-Claisen rearrangement occurs preferentially via a chair-like transition state (Scheme 22). Methyl substitution at C(3′) in the allyl chain hinders the thermal amino-Claisen-rearrangement almost completely, since heating of (E)-and (Z)- 16 , in MBO at 335° leads to the formation of the expected 2-(1′-methyl-allyl) aniline (33) to an extent of only 12 and 5%, respectively (Scheme 9). The main reaction (?60%) represents the splitting into aniline. This is the only observable reaction in the case of 17 . The inversion of the allyl chain in 16 - (E)- and (Z)- 30 cannot be detected - indicated that 33 is also formed in a [3, 3]-sigmatropic process. This is also true for the thermal transformation of N-allyl- (1) and N-allyl-N-methylaniline (15) into 2 and 34 , respectively, since the thermal rearrangement of 2′, 3′, 3′-d₃- 1 yields 1′, 1′, 2′-d₃- 2 exclusively (Table 8). These reaction are accompanied to an appreciable extent by homolysis of the N, C (1′) bond: compound 1 yields up to 40% of aniline and 15 even 60% of N-methylaniline ((Scheme 10 and 11). The activation parameters were determined for the thermal rearrangements of 1, 5, 12 and 15 in MBO (Table 22). All rearrangements show little solvent dependence (Table 5, 7 and 9). The observed ΔH^≠ values are in the range of 34-40 kcal/mol and the ΔS^≠ values very between -13 to -19 e.u. These values are only compatible with a cyclic six-membered transition state of little polarity. - Acid catalysed rearrangements. - The rearrangement of the N-(1′, 1′-dimethylallyl) anilines 5-10 occurs in 2N sulfuric acid already at 50-70° to give te 2-(3′-methyl-2′-butenyl)anilines 22-27 accompanied by their hydrated forms, i.e. the 2-(3′-hydroxy-3′-methylbutyl) anilines 35-40 (Tables 10 and 11). The latter are no more present when the rearrangement is conducted in 0.1 N sulfuric acid, whilst the rate of rearrangement is practically the same as in 2 N sulfuric acid (Table 12). The acid catalysed rearrangements take place with almost no splitting. The SKIDI of the rearrangement of 5 and 2′, 3′, 3′-d₃- 5 is 0.84±0.08 (2 N H₂SO₄, 67, 5°, cf. Table 13) and thus in accordance with a [3,3]-sigmatropic process which occurs in the corresponding anilinium ions. Consequently, the rearrangement of a 1:1 mixture of 2′, 3′, 3′-d₃- 5 and 3, 5-d₂- 5 in 2 N sulfuric acid at 67, 5° occurs without the formation of cross-products (Scheme 13). In the acid catalysed rearrangement of the N-1′-methylallyl) anilines 12-14 at 105-125° in 2 N sulfuric acid the corresponding (E)- and (Z)-anilines are the only products formed (Table 14 and 15). Again no splitting is observed. Furthermore, a dependence of the observed (E)/(Z) ratio and the bulkiness of the o-substituent ( H : (E)/(Z)- 30 = 6.5; t- C ₄ H ₉: (E)- 32 /(Z)- 32 = 90; cf. Table 15) indicates that also in the ammonium-Claisen rearrangement a chair-like transition state is preferentially adopted. In contrast to the thermal rearrangement the acid catalysed transformation in 2 N-O, 1 N sulfuric acid (150-170°) of (E)- and (Z)- 16 as well as of 1 and 15 , occurs very cleanly to yield the corresponding 2-allylated anilines 33, 2 and 34 (Scheme 15 and 18). The amounts of the anilines formed by splitting are <2%. During longer reaction periods hydration of the allyl chain of the products occurs, and in the case of the rearrangement of (E)- and )Z)- 16 the indoline 45 is formed (Scheme 15 and 18). All transformations occur with inversion of the allyl chain. This holds also for the rearrangement of 1 , since 3′, 3′-d₂- 1 gives only 1′, 1′-d₂- 2 (Scheme 17). The activation parameters were determined for the acid catalysed rearrangement of 1, 5, 12 and 15 in 2 N sulfuric acid (Table 22). The ΔH^≠ values of 27-30 kcal-mol and the ΔS^≠ values of +9 to -12 e.u. are in agreement with a [3, 3]-sigmatropic process in the corresponding anilinium ions. The acceleration factors (k_H+/k_Δ) calculated from the activation parameters of the acid catalysed and thermal rearrangements of the anilines are in the order of 10⁵ - 10⁷. They demonstrate that the essential driving force of the ammonium-Claisen rearrangement is the ‘delocalisation of the positive charge’ in the transition state of these rearrangements (cf. Table 23). Solvation effects in the anilinium ions, which can be influenced sterically, also seem to play a role. This is impressively demonstrated by N-(1′, 1′-dimethylallyl)-2, 6-dimethylaniline (11) : its rearrangement into 4-(1′, 1′-dimethylallyl)-2, 6-dimethylaniline (43) cannot be achieved thermally, but occurs readily at 30° in 2 N sulfuric acid. From a preparative standpoint the acid catalysed rearrangement in 2 N-0, 1 N sulfuric acid of N-allylanilines into 2-allylanilines, or if the o-positions are occupied into 4-allylanilines, is without doubt a useful synthetic method (cf. also [17]).     

Methylierung von 4-Hydroxy-4-(2-piperidyl)-4H-pyrazolo [1,5-a]indol mit Formaldehyd und Ameisensäure. 11. Mitteilung über metallorganische Reaktionen und Folgeprodukte

In the 10^th communication of this series [1] the synthesis of 4-hydroxy-4-(2-piperidyl)-4H-pyrazolo[1,5-a]indole ( 4 ) was described (Scheme). Surprisingly enough, methylation of this compound with formaldehyde and formic acid led via ring closure and a subsequent rearrangement to a pentacyclic ketone. By means of ¹³C-NMR.-spectroscopy and mass spectroscopy, this ketone could be identified as a indolizino-pyrazolo-indole ( 9 ). Its structure and configuration were determined by X-ray structure analysis.     

Total Synthesis of Dimethyl Glolosiphone A via α-Carbonyl Radical Spiro-Cyclization

A general approach toward spiro[4.4]nonane structure based on the α-carbonyl radical cyclization has been developed. Efficient total synthesis of dimethyl gloiosiphone A ( 2 ) was achieved. Thus, alkylation of the anion of dimethylhydrazone of cyclopentanone with 5-iodopent-1-yne followed by hydrolysis gave ketone 4 . Iodination of 4 via its TMS-enol ether yielded iodo ketone 7 . Radical spiro-cyclization of 7 gave spiro ketone 10 . Iodination of 10 afford iodo spiro ketone 23 . Oxidation and iodination of 23 gave compound 24 . Methylation of 24 furnished methoxy iodo enone 25 . Substitution of iodide in 25 with methoxide produced dimethoxy enone 26 . Allylic oxidation of 26 gave diketone 27 . Treatment of 27 with OsO₄ and N-methylmorpholine N-oxide gave dihydroxy ketone 28 . Methylation of the primary alcohol group in 28 afforded dimethyl gloiosiphone A ( 2 ).     

Photocyclisierungen von 1, 1'-Polymethylen-di-2-pyridonen. 46. Mitteilung über Photoreaktionen

Photocyclization of 1, 1′-Polymethylene-di-2-pyridones . Benzophenone sensitized irradiation of the four dipyridones 1-4 gave the internal photocyclization products 6 (64%, Scheme 4), 7 (60%, Scheme 5), 8 (Scheme 6), and 11 (26%, Scheme 7), respectively. The decamethylene compound 5 yielded only polymeric material. The primary [2+2] photoproduct 8 from dipyridone 3 (Scheme 6) is relatively unstable. Further irradiation or heating to 65° induced a Cope rearrangement to give compound 9 which, on heating to 137°, was converted into the isomeric compound 10 . This product, as well as the other photoproducts mentioned, are rearranged back to their respective starting materials upon direct irradiation with 254 nm light or by heating to higher temperatures. The various possibilities for cycloadditions of pyridones are discussed as well as the possible factors which are responsible for the highly regioselective photoreactions of the dipyridones 1–4 .     

Umamidierungsreaktionen an cyclischen Amino-amid-Systemen. 3. Mitteilung über Umamidierungsreaktionen

Transamidation Reactions with Cyclic Amino-amides Lactames which are substituted at the nitrogen atom by a 3-aminopropyl residue are transformed under base catalysis to cyclic amino-amides enlarged by 4 ring atoms. The formed ring must be at minimum 12-membered. Scheme 2 illustrates this result: the 8-membered 7 is transamidated in 96% yield to the 12-membered ring 8 (in the presence of potassium 3-aminopropylamid in 1, 3-propanediamine), the 9-membered 10 to the 13-membered ring 11 (97%) and the 11-membered 14 to the 15-membered ring 15 . Furthermore, the 13-membered ring 27 (Scheme 5) is transformed to the 17-membered 28 . In the case of the 15-membered lactame 15 it is demonstrated that 14 is not formed back under the conditions of the transamidation. Large ring lactames which are substituted at the nitrogen atom by a 3-(alkylamino) propyl group lead under base catalysis to an equilibrium mixture, e.g. the 17-membered 26 is in equilibrium with the 21-membered 29 . This result is similar to the behavior of the corresponding open-chain amino-amides [2]. Because of transannular interactions, the 11-membered ring 2 is not stable: transamidation of the 7-membered 1 (Scheme 1) doesn't give the expected 2 , but its water elimination product 3 in small yield. The N-tosyl derivative of 2 , namely 20 , is synthesized by an independent route (Scheme 3). Detosylation of 20 yields the 7-membered 1 instead of 2 . Concerning the mechanism of this interesting reaction see Scheme 4.     

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.     

Die stereoisomeren Sinensiaxanthine und Sinensiachrome: Trennung und Bestimmung ihrer absoluten Konfiguration. 7. Mitteilung über Rosenfarbstoffe

Stereoisomeric Sinensiaxanthins and Sinensiachromes: Separation and Absolute Configuration The so-called sinensiaxanthins and sinensiachromes, important apocarotenols from various fruits, have been separated into 2 and 4 stereoisomers, respectively, and their absolute configurations have been determined: (3S,5R,6S)-5,6-epoxy-5,6-dihydro-10′-apo-β-carotene-3,10′-diol ( 2 ), its (9Z)-stereoisomer 7, the (8R)- and (8S)-epimers of (3S, 5R)-5,8-epoxy-5,8-dihydro- 10′ -apo-β-carotene-3, 10′-diol ( 4 and 5 ), and their (9Z)-stereoisomers 3 and probably 6. Thus, sinensiaxanthins are cleavage products from (Z/E)-isomeric antheraxanthins or violaxanthins (scission at C(9′)–C(10′)) and sinensiachromes analogously from mutatoxanthins or auroxanthins.     

Photoinduzierte Reaktionen von 3-Phenyl-2H-azirinen mit Carbonsäureestern 40. Mitteilung über Photoreaktionen

Irradiation (280–350 nm light) of a benzene solution of 3-phenyl-2H-azirines 1a – e in the presence of carboxylate esters, whose carbonyl groups are activated by electron withdrawing groups situated in the acyl or alkyl moiety, produces 5-alkoxy-3-oxazolines (Tab. 1 and 4, Scheme 2) isolated in 18–82% yield. These heterocycles undoubtedly originate by regiospecific addition of the ester carbonyl group to the azirine-derived benzonitrile-methylide ‘dipole’ (Scheme 1). The 5-(2,′ 2′, 2′-trifluoroethoxy)-3-oxazolines, derived from 2′, 2′, 2′-trifluoroethyl carboxylic esters, on treatment with methanolic hydrogen chloride at low concentration, are smoothly transformed into the corresponding 5-methoxy-3-oxazolines (e.g. 16 → 17 , Tab. 5). Utilizing this process, various hitherto relatively unknown 9. 5-alkoxy-3-oxazolines become accessible. The constitution of the adducts is based essentially on spectral data. The structure of trans-5-methoxy-2,4-diphenyl-5-trifluoromethyl-3-oxazoline (trans- 14 ), the addition product of methyl trifluoroacetate and the benzonitrile-benzylide from 2,3-diphenyl-2H-azirine ( 1d ), was determined by X-ray crystallography (Section 5). Benzonitrile-isopropylide ( 22 ), resulting from the photochemical transformation of 2,2-dimethyl-3-phenyl-2H-azirine ( 1a ), also reacts with S-methyl thiobenzoate to give 2,2-dimethyl-5-methylthio-4,5-diphenyl-3-oxazoline ( 26 ). Ethyl cyanoacetate protonates predominantly the dipolar species derived from 1a at the nitrile C-atom and yields after work-up ethyl α-cyano-cinnamate ( 29 ) and ethyl isopropylidene-cyanoacetate ( 30 ) (Scheme 4). The relative rate of addition (k_rel) of benzonitrile-isopropylide ( 22 ) to methyl α-haloacetates and dimethyl oxalate was determined by competition experiments (Section 6). Log k_rel correlated satisfactorily (r = 0.97) with the pK_a of the acide derived from the ester reactant: log k_rel = ? 1.72 pK_a + 2.58 or with Taft's substituent constants σ*: log k_rel = 2.06 σ* ? 4.11 [k_rel(methyl dichloroacetate) = 1; Section 7.1]. On the basis of the results obtained, the mode of reaction of the so-called benzonitrile-methylide ‘dipole’ is discussed and a model for the transition state of addition of ester-carbonyl groups is proposed that accounts for the observed regiospecifity and steroselectivity.     

Synthesis of (−)‐Erythrodiene and (+)‐7‐Epispirojatamol via Intramolecular Pd‐Catalyzed Allylzincation

Two spirobicyclic sesquiterpenoids, (−)‐erythrodiene ( 1 ) and (+)‐7‐epispirojatamol ( 30 ), were synthesized in enantiomerically pure form via an intramolecular allylzincation process. The allylzinc species were formed in the presence of Et₂Zn via transmetallation of a catalytically generated allylpalladium intermediate. Several Pd catalysts were tested for this transformation, and [Pd(OAc)₂]/Bu₃P (1 equiv.) was found to be, by far, the most effective. Whereas the preparation of 1 involved allylzincation of a tethered terminal olefin, 30 was formed via a novel intramolecular allyl zincation of a methyl ketone. Both reactions showed the same stereochemical preference, yielding the spirobicyclic products in 95 : 5 and 4 : 1 diastereoisomer ratios, respectively.     

Synthese von (±)-Muscopyridin über eine C-ZIP-Ringerweiterungsreaktion

Synthesis of (±)-Muscopyridine via C-ZIP Ring Enlargement Treatment of 4-(1-nitro-2-oxocyclododec-1-yl)butanal ( 1 ) and of its methyl derivative 5 with pentylamine in EtOH at room temperature gave the ring-enlarged aminomethylidene derivatives 6 and 7 , respectively (Scheme 1). After hydrolysis of the aminomethylidene group in 6 and 7 and deformylation followed by a reductive Nef-type reaction, the macrocyclic diketones 10 and 11 , respectively, were obtained. They were transformed by a modified Hantzsch procedure to the title compound (±)-muscopyridine ( 13 ) and normuscopyridine ( 12 ), respectively.     

Nucleotides. Part XLVI. The synthesis of phospholipid conjugates of antivirally active nucleosides by the improved phosphoramidite methodology

The application of the improved phosphoramidite strategy for the synthese of oligonucleotides using β-eliminating protecting groups to phospholipid chemistry offers the possibility to synthesize phospholipid conjugates of AZT ( 6 ) and cordycepin. The synthesis of 3′-azido-3′-deoxythymidine ( 6 ) was achieved by a new isolation procedure without chromatographic purification steps in an overall yield of 50%. Protected cordycepin ( = 3′-de-oxyadenosine) derivatives, the N⁶,2′-bis[2-(4-nitrophenyl)ethoxycarbonyl]cordycepin ( 12 ) and the N⁶,5′-bis[2-(4-nitrophenyl)ethoxycarbonyl]cordycepin ( 13 ) wre prepared by known methods and direct acylation of N⁶-[2-(4-nitrophenyl)ethoxycarbonyl]cordycepin ( 9 ), respectively. These protected nucleosides and the 3′-azido-3′-de-oxythymidine ( 6 ) reacted with newly synthesized and properly characterized lipid-phosphoramidites 21–25 , catalyzed by 1H-tetrazole, to the corresponding nucleoside-phospholipid conjugates 26–38 in high yield. The deprotection was accomplished via β-elimination with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in aprotic solvents to give analytically pure nucleoside-phospholipid diesters 39–51 as triethylammonium or sodium salts. The newly synthesized compounds were characterized by elemental analyses and UV and ¹H-NMR spectra.     

Nucleotides. Part XLV. Synthesis of new (2′–5′)adenylate trimers,containing 5′-amino-5′-deoxyadenosine residues at the 5′-end of the oligoadenylate chain,and of its analogues,carrying a 9-[(2-hydroxyethoxy)methyl]adenine residue at the 2′-terminus

The 5′-amino-5′-deoxy-2′,3′-O-isopropylideneadenosine ( 4 ) was obtained in pure form from 2′,3′-O-isopropylideneadenosine ( 1 ), without isolation of intermediates 2 and 3 . The 2-(4-nitrophenyl)ethoxycarbonyl group was used for protection of the NH₂ functions of 4 (→7) . The selective introduction of the palmitoyl (= hexadecanoyl) group into the 5′-N-position of 4 was achieved by its treatment with palmitoyl chloride in MeCN in the presence of Et₃N (→ 5 ). The 3′-O-silyl derivatives 11 and 14 were isolated by column chromatography after treatment of the 2′,3′-O-deprotected compounds 8 and 9 , respectively, with (tert-butyl)dimethylsilyl chloride and 1H-imidazole in pyridine. The corresponding phosphoramidites 16 and 17 were synthesized from nucleosides 11 and 14 , respectively, and (cyanoethoxy)bis(diisopropylamino)phosphane in CH₂Cl₂. The trimeric (2′–5′)-linked adenylates 25 and 26 having the 5′-amino-5′-deoxyadenosine and 5′-deoxy-5′-(palmitoylamino)adenosine residue, respectively, at the 5′-end were prepared by the phosphoramidite method. Similarly, the corresponding 5′-amino derivatives 27 and 28 carrying the 9-[(2-hydroxyethoxy)methyl]adenine residue at the 2′-terminus, were obtained. The newly synthesized compounds were characterized by physical means. The synthesized trimers 25–28 were 3-, 15-, 25-, and 34-fold, respectively, more stable towards phosphodiesterase from Crotalus durissus than the trimer (2′–5′)ApApA.     

Chemie von α-Aminonitrilen. 13. Mitteilung. Über die Bildung von 2-Oxoethyl-phosphaten (“Glycoladehyd-phosphaten”) aus rac-Oxirancarbonitril und anorganischem Phosphat und über (formale) Konstitutionelle Zusammenhänge zwischen 2-Oxoethyl-phosphaten und Oligo (hexo- und pentopyranosyl)nucleotid-Rückgraten

Chemistry of α-Aminonitriles. Formation of 2-Oxoethyl Phosphates (“Glycolaldehyde Phosphates”) from rac-Oxiranecarbonitrile and on (Formal) Constitutional Relationships between 2-Oxoethyl Phosphates and Oligo(hexo- and pentopyranosyl)nucleotide Backbones Oxiranecarbonitrile in basic acqueous solution at room temperature reacts regioselectively with inorganic phosphate to give the cyanohydrin of 2-oxoethyl phosphate (“glycolaldehyde phosphate”), a source of (the hydrate of) the free aldehyde, preferably in the presence of formaldehyde. In aqueous phosphate solution buffered to nearly neutral pH, oxiranecarbonitrile produces the phosphodiester of glycoladehyde as its bis-cyanohydrin in good yield. In contrast to mono- and dialkylation, trialkylation of phosphate with oxiranecarbonitrile is difficult, and the triester derivative is highly sensitive to hydrolysis. Glycolaldehyde phosphate per se is of prebiotic interest, since it had been shown [5] to aldomerize in basic aqueous solution regioselectively to rac-hexose 2, 4, 6-triphosphates and – in the presence of formaldehyde - mainly to rac-pentose 2, 4-diphosphates with, under appropriate conditions, rac-pentose 2, 4-diphosphates as the major reaction product. However, the question as to whether oxiranecarbonitrile itself has the potential of having been a prebiological natural constituent remains unanswered. Backbone structures of hexopyranosyl-oligonucleotides with phosphodiester linkages specifically between the positions 6′ → 4′, 6′ → 2′, or 4′ → 2′ of the sugar residues can formally be derived via the (hypothetical) aldomerization pathway, a combinatorial intermolecular aldomerization of glycoladehyde phosphate and bis(glycolaldehyde)-phosphodiester in a 1: 1 ratio. The constitutional relationships revealed by this synthetic analysis has played a decisive role as a selection criterion in the pursuit of our experimental studies toward a chemical etiology of the natural nucleic acids' structure. The Discussion in this paper delineates how the analysis contributed to the conception of the structure of p-RNA. The English Footnotes to Schemes 1–11 provide an extension of this summary.     

Technische Verfahren zur Synthese von Carotinoiden und verwandten Verbindungen aus 6-Oxo-isophoron. VI. Synthese Von Rhodoxanthin und (3-RS, 3′RS)-Zeaxanthin; Zugänge zur C15-Ringkomponente über 3-Oxo-jonon-Derivate

Technical Procedures for the Synthesis of Carotenoids and Related Compounds from 6-Oxo-isophorone, VI. Synthesis of Rhodoxanthin and (3RS, 3′RS)-Zeaxanthin; Routes to the C₁₅-Ring Component via 3-Oxo-ionone Derivatives The C₁₅-ring component 4 , key intermediate of a new scheme for the synthesis of rhodoxanthin ( 1 ) and (3RS, 3RS)-zeaxanthin ( 3 ), has been synthesized starting from 6-oxo-isophorone ( 7 ) via 3-oxo-cyclocitral and 3-oxo-ionone derivatives.     

Photoinduzierte Cycloadditionen von aliphatischen 2H-Azirinen. 37. Mitteilung über Photoreaktionen

The purely aliphatic 2,3-dipropyl-2H-azirine ( 1 ) reacts on irradiation with a mercury high-pressure lamp through a Vycor filter with methyl trifluoroacetate or acetone to form 3-oxazolines 3a, b (65%) resp. 4 (14%) (Scheme 1). 9-Azabicyclo[6.1.0]non-1(9)-ene ( 5 ) on irradiation in the presence of the dipolarophiles methyl trifluoroacetate, methyl difluoroacetate, 1,1,1-trifluoro-propanone and acetone behaves in a similar way, whereby the corresponding bicyclic 3-oxazolines 7–10 result in yields of 60–20% (Scheme 2). By analogy with the photochemical behaviour of 3-aryl-2H-azirines it is assumed that nitrile-ylides 2 resp. 6 represent intermediates. In fact irradiation of 2,3-dipropyl-2H-azirine ( 1 , λ_max 239 nm, ? 240) at ?196° with light of wavelength 245 nm in a hydrocarbonglass gives rise to a pronounced maximum at 280 nm, for which an ? of ? 15000 can be estimated. The quantum yield for the formation of nitrile-methylide 2 is 0,8. Irradiation of the dipole 2 at ?196° or warming to ?150° causes the maximum at 280 nm to disappear.     

Photochemie von tricyclischen β, γ-γ′, δ′-ungesättigten Ketonen. 50. Mitteilung über Photoreaktionen

Photochemistry of tricyclic β, γ-γ′, δ′-unsaturated ketones The easily available tricyclic ketone 1 (cf. Scheme 1) with a homotwistane skeleton yielded upon direct irradiation the cyclobutanone derivative 3 by a 1,3-acyl shift. Further irradiation converted 3 into the tricyclic hydrocarbon 4 . However, acetone sensitized irradiation of 1 gave the tetracyclic ketone 5 by an oxa-di-π-methane rearrangement. Again with acetone as a sensitizer the ketone 5 was quantitatively converted to the pentacyclic ketone 6 . The conversion 5 → 6 represents a novel photochemical 1,4-acyl shift. The possible mechanisms are discussed (see Scheme 7). The tricyclic ketone 2 underwent similar types of photoreactions as 1 (Scheme 2). Unlike 5 the tetracyclic ketone 9 did not undergo a photochemical 1,4-acyl shift. The epoxides 10 and 14 derived from the ketones 1 and 2 , respectively, underwent a 1,3-acyl shift upon irradiation followed by decarbonylation, and the oxa-di-π-methane rearrangement (Schemes 3 and 4). The diketone 18 derived from 1 behaved in the same way (Scheme 5). The tetracyclic diketone 21 cyclized very easily to the internal aldol product 22 under the influence of traces of base (Scheme 5). Upon irradiation the γ, δ-unsaturated ketone 24 underwent only the Norrish type I cleavage to yield the aldehyde 25 (Scheme 6).     

Nucleotides. Part XXXI. Modified Oligomeric 2′–5′ A Analogues: Synthesis of 2′–5′ oligonucleotides with 9-(3′-azido-3′-deoxy-β-D-xylofuranosyl)adenine and 9-(3′-amino-3′-deoxy-β-D-xylofuranosyl)adenine as modified nucleosides

A series of new 2′–5′ oligonucleotides carrying the 9-(3′-azido-3′deoxy-β-D-xylofuranosyl)adenine moiety as a building block has been synthesized via the phosphotriester method. The use of the 2-(4-nitrophenyl)ethyl (npe) and 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) blocking groups for phosphate, amino, and hydroxy protection guaranteed straightforward syntheses in high yields and easy deblocking lo form the 2′–5′ trimers 21 , 22 , and 25 and the tetramer 23 . Catalytic reduction of the azido groups in [9-(3′-azido-3′-deoxy-β-D-xylofuranosyl)adenine]2′-yl-[2′-(O^p-ammonio)→ 5′]-[9-(3′-azido-3′-deoxy-β-D-xylofuranosyl)adenin]-2′-yl-[2′-(O^p-ammonio)→ 5′]-9-(3′-azido-3′-deoxy-β-D-xylofuranosyl)adenine ( 21 ) led to the corresponding 9-(3′-amino-3′-deoxy-β-D-xylofuranosyl)-adenine 2′–5′ trimer 26 in which the two internucleotidic linkages are formally neutralized by intramolecular betaine formation.     

Selektive Herstellung von l- oder u-Aldolen aus Äthyl-trityl-keton und aromatischen Aldehyden über Lithium- bzw. Aluminium-Enolate

Selective Preparation of l- or u-Aldols from Ethyl Trityl Ketone and Aromatic Aldehydes through Lithium and Aluminium Enolates, Respectively The ethyl trityl ketone ( 1 ) is deprotonated to the (Z)-enolate 2 which adds to aromatic aldehydes with relative topicity ul to give the aldols 3 (?78°, THF, kinetic control). If, on the other hand, 1 is heated with trimethylaluminium in toluene, the aluminium enolate formed combines with aromatic aldehydes and with cinnamic aldehyde with opposite relative topicity (lk) to the aldols 5 (+20°, toluene, 2 d, precipitation of the aluminium aldolate 4 , thermodynamic control). The mechanism is discussed (cf. Fig. 1). The adducts to benzaldehyde ( 3a , 5a ), furfural ( 3f , 5f ), and cinnamaldehyde ( 3i , 5i ) are O-(2-methoxyethoxy)methyl (MEM) protected and cleaved by lithium triethylborohydride to the 1,3-diol derivatives 9–11 with a free primary and a protected secondary OH-group. Analogous conversions of 1 and other ketones may also be diastereoselective, but turned out to be of less preparative value (see 6–8 , 12 ).     

Das unterschiedliche massenspektrometrische Fragmentierungsverhalten von Lysinmethylester und dessen N,N′-Diacetylderivat. 27. Mitteilung über das massenspektrometrische Verhalten von Stickstoffverbindungen

The Different Behaviour of Lysine Methyl Ester and its N,N′-Diacetyl Derivative under Electron Impact The base peak in the spectrum of lysine methyl ester is due to the fragment ion C₅H₁₀N (m/e 84), for which the cyclic structure g (Scheme 1) is deduced. During its formation from the [M-COOCH₃]-ion an equilibration of both nitrogen atoms takes place (ion c , Scheme 1). The cyclic nature of ion m/e 84 is in agreement with the intensity of the corresponding ions in the spectra of homologues of lysine methyl ester (Fig. 1). Although in comparison with lysine methyl ester ( 1 ) N,N′-diacetyl-lysine methyl ester ( 7 ) shows the same general fragmentation pathway with formation of the ions [M-COOCH₃] and [M-COOCH₃-H₂NCOCH₃] (m/e 126), the exact fragmentation mechanism proves to the different. Two mechanisms are discussed for the formation of the ion m/e 126 from 7 (Schemes 2 and 3). The results are based on the spectra of labelled derivatives.