Some reactions of 4-[(2′,3′-diphenyl-6′-methoxy-5′-benzofuranyl)-methylene]- and 4-[(2′,3′-diphenyl-5′-methoxy-6′-benzofuranyl)-methylene]-2-phenyloxazolin-5-one

2,3-Diphenyl-5-formyl-6-methoxybenzofuran was reacted with hippuric acid to give 4-[(2′,3′-diphenyl-6′-methoxy-5′-benzofuranyl)methylene]-2-phenyloxazolin-5-one. The above mentioned oxazolone yielded 2,3-diphenyl-6-methoxybenzofuranylacetic acid by reaction with hydrazine hydrate, nitrous acid, benzene followed by acid hydrolysis. The reactions of the oxazolone with hydroxylamine hydrochloride and primary or secondary amines were also investigated.     

Synthese und Chiralität von (5R, 6R)-5,6-Dihydro-β, ψ-carotin-5,6-diol, (5R, 6R, 6′R)-5,6-Dihydro-β, ε-carotin-5,6-diol, (5S, 6R)-5,6-Epoxy-5,6-dihydro-β, ψ-carotin und (5S, 6R, 6′R)-5,6-Epoxy-5,6-dihydro-β,ε-carotin

Synthesis and Chirality of (5R, 6R)-5,6-Dihydro-β, ψ-carotene-5,6-diol, (5R, 6R, 6′R)-5,6-Dihydro-β, ε-carotene-5,6-diol, (5S, 6R)-5,6-Epoxy-5,6-dihydro-β,ψ-carotene and (5S, 6R, 6′R)-5,6-Epoxy-5,6-dihydro-β,ε-carotene Wittig-condensation of optically active azafrinal ( 1 ) with the phosphoranes 3 and 6 derived from all-(E)-ψ-ionol ( 2 ) and (+)-(R)-α-ionol ( 5 ) leads to the crystalline and optically active carotenoid diols 4 and 7 , respectively. The latter behave much more like carotene hydrocarbons despite the presence of two hydroxylfunctions. Conversion to the optically active epoxides 8 and 9 , respectively, is smoothly achieved by reaction with the sulfurane reagent of Martin [3]. These syntheses establish the absolute configurations of the title compounds since that of azafrin is known [2].     

Cycloviolaxanthin (= (3S,5R,6R,3′S,5′R,6′R)-3,6:3′,6′-Diepoxy-5,6,5′,6′-tetrahydro-β,β-carotin-5,5′-diol), ein neues Carotinoid aus Paprika (Capsicum annuum)

Cycloviolaxanthin (= (3S,5R,6R,3′S,5′R,6′R)-3.6:3′,6′-Diepoxy-5,6,5′,6′-tetrahydro-β,β-carotene-5,5′-diol), a Novel Carotenoid from Red Paprika (Capsicum annuum) From red paprika (Capsicum annuum var. longum nigrum) cycloviolaxanthin was isolated as a minor carotenoid and, based on spectral data, assigned the symmetrical structure 8 .     

Carotinoide mit 7-Oxabicyclo[2.2.1]heptyl-Endgruppen. Teil II. Synthese von (2S,5R,6S,2′S,5′R,6′S)-2,5:2′5′-Diepoxy-5,6,5′,6′-tetrahydro-β,β-carotin

Carotenoids mit 7-Oxabicyclo[2.2.1]heptyl-End Groups. Synthesis of (2S,5R,6S,2′S,5′R,6′S)-2,5:2′5′-Diepoxy-5,6,5′,6′-tetrahydro-β,β-carotene Mukayama's ester 6 (methyl (1S,2R,5S)-2,5-epoxy-2,6,6-trimethylcyclohexane-1-carboxylate) was transformed in a few conventional steps into the title compound 14 . Its CD curve was found to be significantly different from that of the analogous 3,6-epoxide, a fact we tentatively lake as an indication of a (weak) electronic interaction between the ring O-atom and the π-orbitals of the polyene chain.     

Nucleoside und Nucleotide. Teil 16. Verhalten von 1-(2′-Desoxy-β-D-ribofuranosyl)-2(1 H)-pyrimidinon-5′-triphosphat, 1-(2′-Desoxy-β-D-ribofuranosyl)-2(1 H)pyridinon-5′-triphosphat und 4-Amino-1-(2′-Desoxy-β-D-ribofuranosyl)-2(1 H)-pyridinon-5′-triphosphat gegenüber DNA-Polymerase

Nucleosides and Nucleotides. Part 16. The Behaviour of 1-(2′-Deoxy-β-D -ribofuranosyl)-2(1H)-pyrimidinone-5′-triphosphate, 1-(2′-Deoxy-β-D -ribofuranosyl-2(1H))-pyridinone-5′-triphosphate and 4-Amino-1-(2′-desoxy-β-D -ribofuranosyl)-2(1H)-pyridinone-5′-triphosphate towards DNA Polymerase The behaviour of nucleotide base analogs in the DNA synthesis in vitro was studied. The investigated nucleoside-5′-triphosphates 1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyrimidinone-5′-triphosphate (pppM_d), 1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyridinone-5′-triphosphate (pppII_d) and 4-amino-1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyridinone-5′-triphosphate (pppZ_d) can be considered to be analogs of 2′-deoxy-cytidine-5′-triphosphate. However, their ability to undergo base pairing to the complementary guanine is decreased. When pppM_d, pppII_d or pppZ_d are substituted for pppC_d in the enzymatic synthesis of DNA by DNA polymerase no incorporation of these analogs is observed. They exhibit only a weak inhibition of the DNA synthesis. The mode of the inhibition is uncompetitive which shows that these nucleotide analogs cannot serve as substrates for the DNA polymerase.     

Electron Attachment to Hydrated Oligonucleotide Dimers: Guanylyl‐3′,5′‐Cytidine and Cytidylyl‐3′,5′‐Guanosine

The dinucleoside phosphate deoxycytidylyl‐3′,5′‐deoxyguanosine (dCpdG) and deoxyguanylyl‐3′,5′‐deoxycytidine (dGpdC) systems are among the largest to be studied by reliable theoretical methods. Exploring electron attachment to these subunits of DNA single strands provides significant progress toward definitive predictions of the electron affinities of DNA single strands. The adiabatic electron affinities of the oligonucleotides are found to be sequence dependent. Deoxycytidine (dC) on the 5′ end, dCpdG, has larger adiabatic electron affinity (AEA, 0.90 eV) than dC on the 3′ end of the oligomer (dGpdC, 0.66 eV). The geometric features, molecular orbital analyses, and charge distribution studies for the radical anions of the cytidine‐containing oligonucleotides demonstrate that the excess electron in these anionic systems is dominantly located on the cytosine nucleobase moiety. The π‐stacking interaction between nucleobases G and C seems unlikely to improve the electron‐capturing ability of the oligonucleotide dimers. The influence of the neighboring base on the electron‐capturing ability of cytosine should be attributed to the intensified proton accepting–donating interaction between the bases. The present investigation demonstrates that the vertical detachment energies (VDEs) of the radical anions of the oligonucleotides dGpdC and dCpdG are significantly larger than those of the corresponding nucleotides. Consequently, reactions with low activation barriers, such as those for O? C σ bond and N‐glycosidic bond breakage, might be expected for the radical anions of the guanosine–cytosine mixed oligonucleotides.     

Eine Suche nach 3′-Epilutein ( = (3R,3′S,6′R)-β,ε-Carotin-3,3′-diol) und 3′, O-Didehydrolutein (=(3R, 6′R)-3-Hydroxy-β,ε-carotin-3′-on) in Eigelb,in Blüten von Caltha palustris und in Herbstblättern

Search for the Presence in Egg Yolk, in Flowers of Caltha palustris and in Autumn Leaves of 3′-Epilutein ( =(3R,3′S,6′R)-β,ε-Carotene-3,3′-diol) and 3′,O-Didehydrolutein ( =(3R,6′R)-3-Hydroxy-β,ε-carotene-3′-one) 3′.O-Didehydrolutein ( =(3R, 6′R)-3-hydroxy-β,ε-carotene-3′-one; 2) has been detected in egg yolk and in flowers of Caltha palustris. This is the first record for its occurrence in a plant. The compound shows a remarkable lability towards base; therefore, it may have been overlooked til now, because it is destroyed under the usual conditions of saponification of the carotenoid-esters. One of the many products formed from 2 with 1% KOH in methanol has been purified and identified as the diketone 3 ( =(3R)-3-hydroxy-4′, 12′-retro-β,β-carotene-3′,12′-dione). The identification of this transformation product from lutein might throw a new light on the metabolism of this important carotenoid in green plants. 3′-Epilutein ( =(3R,3′S,6′R)-β,ε-carotene-3,3′-diol; 1) was not detected in egg yolk, but is present besides lutein in flowers of C. palustris, thus confirming an earlier report of the occurrence of an isomeric (possibly epimeric) lutein (‘calthaxanthin’) in that plant [21]. We were not able to detect even traces of 1 or 2 in the carotenoid fraction from autumn leaves of Prunus avium (cherry), Parrotia persica, Acer montanum (maple) and yellow needles of Larix europaea (larch). α-Cryptoxanthin (4) , a very rare carotenoid, was isolated in considerable quantity for the first time from flowers of C. palustris.     

Carotinoide mit 7-Oxabicyclo[2.2.1]heptyl-Endgruppen. Teil I. Versuch einer Synthese von Cycloviolaxanthin (= (3S,5R,6R,3′S,5′R,6′R)-3,6:3′,6′-Diepoxy-5,6,5′,6′-tetrahydro-β,β-carotin-5,5′-diol)

Carotenoids with 7-Oxabicyclo[2,2.1]heptyl End Groups. Attempted Synthesis of Cycloviolaxanthin ( = (3S,5R,6S,3′S,5′R,6′R)-3,6:3′,6′- Diepoxy-5,6,5′,6′-tetrahydro-β,β-carotin-5,5′-diol) Starting from our recently described synthon (+)- 24 , the enantiomerically pure 3,6:4,5:3′,6′:4′,5′-tetraepoxy-4,5,4′,5′-tetrahydro-ε,ε-carotene ( 34 ) and its 15,15′-didehydro analogue 32 were synthesized in eleven and nine steps, respectively (Scheme 4). Chiroptical data show, in contrast to the parent ε,ε-carotene, a very weak interaction between the chiral centers at C(5), C(5′), C(6), C(6′), and the polyene system. Diisobutylaluminium hydride reduction of 32 lead rather than to the expected 15,15′-didehydro analogue 35 of Cycloviolaxanthin ( 8 ), to the polyenyne 36 (Scheme 5). We explain this reaction by an oxirane rearrangement leading to a cyclopropyl ether followed by a fragmentation to an aldehyd on the one side and an enol ether on the other (Scheme 6). This complex rearrangement includes a shift of the whole polyenyne chain from C(6), C(6′) to C(5), C(5′) of the original molecule.     

Nucleic-Acid Analogues with Constraint Conformational Flexibility in the Sugar-Phosphate Backbone (‘Bicyclo-DNA’). Part 1. Preparation of (3S,5′R)-2′-Deoxy-3′,5′-ethano-αβ-D-ribonucleosides (‘Bicyclonucleosides’)

We describe the synthesis of 2′-deoxy-3′,5′-ethano-D -ribonucleosides 1 – 8 (= (5′,8′-dihydroxy-2′-oxabicyclo-[3.3.0]oct-3′-yl)purines or -pyrimidines) of the nucleobases adenine, thymine, cytosine, and guanine. They differ from natural 2′-deoxyribonucleosides only by an additional ethylene bridge between the centers C(3′) and C(5′). The configuration at these centers (3S,5′R) was chosen as to match the geometry of a repeating nucleoside unit in duplex DNA as close as possible. These nucleosides were designed to confer, as constituents of an oligonucleotide chain, a higher degree of preorganization of a single strand for duplex formation with respect to natural DNA, thus leading to an entropic advantage for the pairing process. The synthesis of these ‘bicyclonucleosides’ was achieved by construction of an enantiomerically pure carbohydrate precursor 18 / 19 (Schemes 1), which was then converted to the corresponding nucleosides by known methods in nucleoside synthesis (Schemes 2 and 3). In all cases, both anomeric forms of the nucleosides were obtained in pure crystalline form, the relative configuration of which was established by ¹H-NMR-NOE spectroscopy. A conformational analysis of the nucleosides with β-configuration at the anomeric center by means of X-ray and ¹H-NMR (including NOE) spectroscopy show the furanose part of the molecules to adopt uniformly a 1′exo-conformation with the base substituents preferentially in the anti-range in the pyrimidine nucleosides (anti/syn ca. 2:1) distribution in the purine nucleosides (in solution).     

Nucleosides and Nucleotides. Part 13. Synthesis and spectral properties of 1- (3′-O-Phosphoryl-2′-deoxy-β -D-ribofuranosyl)-2(1H)-pyridone-(3′-5′)-1-(2′-deoxy-β-D-ribofuranosyl)-2 (1H)-pyridone

The dinucleoside phosphate Π_dpΠ_d ( 4 ) was synthesized from the monomers 1-(5′-O-monomethoxytrityl - 2′ - deoxy - β - D - ribofuranosyl) - 2 (1 H) - pyridone ((MeOTr) Π_d, 2 ) and 1-(5′-O-phosphoryl-3′-O-acetyl-2′-deoxy-β-D -ribofuranosyl)-(1H)-pyridone (pΠ_d(Ac), 3 ). Its 6.4% hyperchromicity and an analysis of the ¹H-NMR. spectra indicate that the conformation and the base-base interactions in 4 are similar to those in natural pyrimidine dinucleoside phosphates.     

Asymmetric Synthesis of (S)-5,5,5,5′,5′,5′,5′-Hexafluoroleucine

(S)-5,5,5,5′,5′,5′-Hexafluoroleucine ((S)- 13 ) of 81 % ee is prepared from hexafluoroacetone ( l ) and ethyl bromopyruvate (= ethyl 2-oxopropanoate) in 7 steps with an overall yield of 18% (Schemes 1 and 2). Key step in this sequence is the highly enantioselective reduction of the carbonyl group in α-keto ester 4 either by bakers' yeast (91 % ee) or by ‘catecholborane’ 6 utilizing an oxazaborolidine catalyst, yielding hydroxy ester (R)- 5 with 99% ee. The absolute configuration was determined by X-ray analysis of the HCl adduct (S,R)- 9b of (2S)-N-[(R)- l-phenylethyl]-5,5,5,5′,5′,5′-hexafluoroleucine ethyl ester.     

A convenient one-step synthesis of 6-selenoxo-9-(β-D-ribofuranosyl)purine 3′,5′-cyclic phosphate and related compounds

A useful, facile procedure for preparing seleno-heterocyclic compounds is reported. Treatment of cAMP, AMP, adenosine, 2-aminoadenosine, adenine arabinoside and formycin with hydrogen selenide in aqueous pyridine at 65° for 1.5-5 days gave the corresponding seleno compounds in good yield, while these compounds were relatively inert to hydrogen sulfide. A reaction mechanism is proposed.     

1,2-Epoxycarotinoide. 2. Mitteilung. Synthese der 1′,2′-Epoxide von β,ψ- und ε,ψ-Carotin (= γ- bzw. δ-Carotin)

The synthesis of the naturally occurring 1′,2′-epoxy-1′,2′-dihydro-β, δ-carotene and 1′,2′-epoxy-1′,2′-dihydro-ε, ψ-carotene is described.     

Nucleoside und Nucleotide. Teil 10. Synthese von Thymidylyl-(3′-5′) -thymidylyl-(3′-5′)-1-(2′-desoxy-β-D-ribofuranosyl)-2(1 H)-pyridon

Nucleosides and Nucleotides. Part 10. Synthesis of Thymidylyl-(3′-5′)-thymidylyl-(3′-5′)-1-(2′-deoxy-β-D - ribofuranosyl)-2(1 H)-pyridone The synthesis of 5′-O-monomethoxytritylthymidylyl-(3′-5′)-thymidylyl-(3′-5′)-1-(2′-deoxy-β-D -ribofuranosyl)-2(1H)-pyridone ((MeOTr)T_dpT_dp∏_d, 5 ) and of thymidylyl-(3′-5′)-thymidylyl-(3′-5′)-1-(2′-deoxy-β-D -ribofuranosyl)-2(1 H)-pyridone (T_dpT_dp∏_d, 11 ) by condensing (MeOTr) T_dpT_d ( 3 ) and p∏_d(Ac) ( 4 ) in the presence of DCC in abs. pyridine is described. Condensation of (MeOTr) T_dpT_dp ( 6 ) with Π_d(Ac) ( 7 ) did not yield the desired product 5 because compound 6 formed the 3′-pyrophosphate. The removal of the acetyl- and p-methoxytrityl protecting group was effected by treatment with conc. ammonia solution at room temperature, and acetic acid/pyridine 7 : 3 at 100°, respectively. Enzymatic degradation of the trinucleoside diphosphate 11 with phosphodiesterase I and II yielded T_d, pT_d and p∏_d, T_dp and Π_d, respectively, in correct ratios.     

Synthesis of 5′-halo-2′,3′-lyxo-epoxy and 2′,3′-unsaturated thieno[3,2-d]pyrimidine nucleosides

A series of thieno[3,2-d]pyrimidine-2,4-dione nucleosides modified in the carbohydrate moiety has been synthesized. In the first part, synthetic routes are described for the replacement of 5′-hydroxyl group in preformed 1-(β-D-ribofuranosyl)thieno[3,2-d]pyrimidine-2,4-dione I by fluoro, iodo or chloro atoms. Reduction of the 5′-iodo substituent of VI was then carried out catalytically using palladium on carbon as catalyst to give the expected 5′-deoxy derivative VIII. The lyxo-epoxide derivative XII was then synthesized by sequential treatment of the 5′-deoxy-5′-chloro derivative X with methanesulfonyl chloride and with sodium hydroxide. In the second part, most of attention has been devoted to apply different methods reported in the literature that allow access to 2′,3′-olefinic derivatives from the corresponding 2′,3′-dihydroxy precursor. The 5′-O-silyl protected bisxanthate XIV either on reduction with tri-n-butyltin hydride or by reductive elimination of the haloacetate XVI afforded the free 2′,3′-olefin nucleoside after removal of the 5′-protecting group. However none of the compounds in this series exhibited significant antiviral activity against HIV at the doses tested.