bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glyconothio‐O‐lactones Part II. Cycloaddition to Dienes, Diazomethane, and Carbenoids
Authors: Hürzeler Marianne , Bernet Bruno , Mäder Thomas , Vasella Andrea 
Published: December 2004

AbstractThe addition of dienes, diazomethane, and carbenoids to the manno‐ and ribo‐configurated thio‐γ‐O‐lactones 1 and 2 was investigated. Thus, 1 (Scheme 1) reacted with 2,3‐dimethylbutadiene (→ 4, 73%), cyclopentadiene (→ 5a/b 1:1, 70%), cyclohexa‐ 1,3‐diene (→ 9a/b 2:3, 92%), and the electron‐rich butadiene 6(→7a/b 3:1, 82%). Wheras 5a/b was separated by flash chromatography, 7a/b was desilylated leading to the thiapyranone 8. Selective hydrolysis of one isopropylidene group of 9a/b and flash chromatography gave 10a and 10b. The structures of the adducts were elucidated by X‐ray analysis (4), by NOE experiments (4, 5a, 5b, 7a/b, 10a, and 10b), and on the basis of a homoallylic coupling (7a/b). The additions occurred selectively from the ‘exo’ ‐side of1. Only a weak preference for the ‘endo’‐adducts was observed. Hydrogenation of 9a/b with Raney‐Ni (EtOH, room temperature) gave the thiabicyclo [2.2.2]octane 11. Under harsher conditions (dioxane, 110°), 9a/b was reduced to the cyclohexyl ß‐DC‐glycoside 12 which was deprotected to 13. X‐Ray analysis of 13 proved that the desulfuration occurred with inversion of the anomeric configuration. The regioselective addition of the dihydropyridine 14 to 1 (Scheme 2) and the methanolysis of the crude adduct 15 gave the lactams 16a (32%) and 16b (38%). Desilylation of 15 with Bu4NF · 3H2O, however, gave the unsaturated piperidinedione 17 (92%) which was deprotected to the tetrol 18 (65%). Similarly, 2 was transformed via 19 (62%) into the triol 20 (74%). The cycloaddition of 1 with CH2N2 (Scheme 3) gave a 35:65 mixture of the 2,5‐dihydro‐ 1,3,4‐triazole 21and the crystalline 4,5‐dihydro 1,2,3‐triazole 22. Treatment of 21 and 22 with base gave the hydroxytriazoles 23 and 24, respectively. The structure of 24 was established by X‐ray analysis. The triazole mixture 21/22 was separated by prep. HPLC at 5°. At room temperature, 21 already decomposed (half‐life 21.6 h) leading in CDCI3 solution to a complex mixture (containing ca. 20–25% of the spirothiirane 27 and ca. 7–10% of its anomer) and in MeOH solution exclusively to the O,O,S‐ortholactone 26. Crystals of 22 proved be stable at 105°. Upon heating in petroleum ether at 100°, 22 was transformed into a ca. 1:1 mixture of 27 and the enol ether 28. The reaction of 1 with ethyl diazoacetate (Scheme 4) in the presence of Rh2(OAc)4. 2H2O gave the unsaturated esters 29 (33%) and 30 (26%), whereas the analogous reaction with diethyl diazomalonate afforded the spirothiirane 31 (68%) and the enol ether 32 (29%). Complete transformation of 31 into 32 was achieved by the treatment with P(NEt2)3. Similary, 33 (69%) was prepared from 2.
Synthesis and Absolute Configuration of the C12‐Terpenoid Dehydrogeosmin from the Flower Scents of Rebutia marsoneri and Dolichothele sphaerica (Cactaceae); a new approach to bis‐angularly substituted trans‐decalins
Authors: Huber Udo , Boland Wilhelm , König Wilfried A. , Gehrcke Bärbel 
Published: December 2004

AbstractOptically pure(+)‐(4S, 4aS, 8aS)‐1,2,3,4,4a,5,8,8a‐octahydro‐4,8a‐dimethylnaphthalen‐4a‐ol((+)‐1; dehydrogeosmin) is released from flower heads of the two cactaceae Rebutia marsoneri and Dolichothele spharica. The absolute configuration of (+)‐1 is identical with that of the known microbial metabolial geosmin (−)‐2. The key reactions of the synthesis of 1 are the kinetically controlled transesterification of the primary alcohol 4 using a lipase from Candida cyclindracea and the stereo‐and regiospecific angular alkylation of a cis‐decalin skeleton by a Lewis‐acid‐assisted ring opening of the quaternary epoxy‐alcohol 3 with MeMgBr/Cul. The sequence provides a new entry into the class of bis‐angularly substituted trans‐decalins.
Synthesis and Monoamine Oxidase Inhibitory Activity of 3‐Substituted 5H‐Indeno[1,2‐c]pyridazines
Authors: Kneubühler Silvia , Testa Bernard , Carta Vincenzo , Altomare Cosimo , Carotti Angelo 
Published: December 2004

AbstractThe one‐pot synthesis of nine 5H‐indeno[1,2‐c]pyridazines is described. These compounds are shown to be potent, reversible inhibitors of monoamine oxidase B (MAO‐B) with little or no effect on monoamine oxidase A (MAO‐A). Qualitative structure‐activity relations indicate that the MAO‐B inhibitory activity is strongly influenced by electronic and bulk properties of substitutents.
8‐Azaguanine 2′,3′‐Dideoxyribonucleosides: Glycosylation of the 5‐amino‐7‐methoxy‐3H‐1,2,3‐triazolo[4,5‐d]pyrimidinyl anion with 2,3‐dideoxy‐D‐glycero‐pentofuranosyl chloride
Authors: Seela Frank , Mersmann Karin 
Published: December 2004

AbstractThe synthesis of the regioisomeric 8‐azaguanine N7‐, N8‐, and N9‐(β‐D‐2′,3′‐dideoxyribonucleosides) (1, 2, and 3, respectively) and of the diamino derivative 13 is described. The anion of 5‐amino‐7‐methoxy‐3H‐1,2,3‐triazolo[4,5‐d]pyrimidine (5) was glycosylated with 5‐O‐[(tert‐butyl)dimethylsilyl]‐2,3‐dideoxy‐D‐glycero‐pentofuranosyl chloride (6; anomeric mixture), yielding the regioisomeric 2′,3′‐dideoxyribofuranosides as anomeric mixtures 7a/10a, 8a/11a, and 9a/12a. They were desilylated with Bu4NF in THF affording the 5‐amino‐7‐methoxy‐nucleosides 7b–12b. Treatment with aqueous NaOH gave the 8‐azaguanine β‐D‐2′,3′‐dideoxynucleosides 1–3 and their α‐D‐anomers 14–16. The reaction of 7b with NH3/MeOH yielded the diamino compound 13. The N‐glycosylic bond of 8‐aza‐2′,3′‐dideoxyguanosine (1) is four‐times more stable against acid than that of 2′,3′‐dideoxyguanosine. Compounds 1, 2, and 13 were converted to their 5′‐triphosphates 17–19 which showed only modest inhibitory activity against HIV‐reverse transcriptase.
Synthesis of a Fullerene Derivative of Benzo[18]crown‐6 by Diels‐Alder Reaction: Complexation Ability, Amphiphilic Properties, and X‐Ray Crystal Structure of a Dimethoxy‐1,9‐(methano[1,2]benzenomethano)fullerene[60] Benzene Clathrate
Authors: Diederich François , Jonas Ulrich , Gramlich Volker , Herrmann Andreas , Ringsdorf Helmut , Thilgen Carlo 
Published: December 2004

AbstractA fullerene derivative 1 of benzo[18]crown‐6 was obtained by Diels‐Alder addition of fullerene[60](C60) to the ortho‐quinodimethane prepared in situ from 4,5‐bis(bromomethyl)benzo[18]crown‐6 (3) with Bu4NI in toluene. Extraction experiments show that the complexation of K+ ions strongly increases the solubility of 1 in protic solvents like MeOH. Using Langmuir‐Blodgett techniques, monolayers of the highly amphiphilic fullerene‐derived crown ether 1 and its K+ ion complex were prepared. An X‐ray crystal structure was obtained from a benzene clathrate of comparison compound 2, synthesized by Diels‐Alder reaction of C60 with the ortho‐quinodimethane derived from 1,2‐bis(bromomethyl)‐4,5‐dimethoxybenzene (4). Both the fullerene molecule 2 and the benzene molecule are fully ordered in a crystal packing which is stabilized by intermolecular van‐der‐Waals contacts between the benzene ring and the C‐spheres, intermolecular C…︁C contacts between the C60 moieties, and intermolecular O…︁C contacts between the O‐atoms of the veratrole moieties and fullerene C‐atoms.
Enantioselective Synthesis of (2S)‐2‐Amino‐3‐(4‐hydroxy‐3‐phosphonophenyl)propionic Acid (= 3′‐Phosphono‐L‐tyrosine) and Its Incorporation into Peptides
Authors: Paladino Joseph , Guyard Christel , Thurieau Christophe , Fauchère Jean‐Luc 
Published: December 2004

AbstractThe asymmetric synthesis of derivatives of the new amino acid (2S)‐2‐amino‐3‐(4‐hydroxy‐3‐phosphono‐phenyl)propionic acid (3′‐phosphono‐L‐tyrosine; Tyr [3′‐PO(OH)2]) is described. The protected amino acid 13 is obtained via a Schöllkopf synthesis by coupling of the rearranged ortho‐phosphonophenolic side chain (see Scheme 1, 6a) with the lithiated bis‐lactim ether 8 of cyclo(‐D‐valyl‐glycyl‐) (see Scheme 2). The incorporation of the protected amino acid 14 in a biologically active dodecapeptide is successfully achieved by the [(9H‐fluoren‐9‐yl)‐methoxy]carbonyl (Fmoc) strategy of solid‐phase peptide synthesis. Differential protection of Tyr[3′‐PO(OH)2] provides four levels of selective deprotection of, in the order, the N2‐amino, the carboxyl (cleavage from the resin), the phenol, and the phosphono function (→ peptide 16).
Regioselective Radical Additions to 7‐Oxabicyclo[2.2.1]hept‐5‐en‐2‐one
Authors: Vionnet Jean‐Paul , Schenk Kurt , Renaud Philippe 
Published: December 2004

AbstractRadical addition to 7‐oxabicylco[2.2.1]hept‐5‐en‐2‐one (1) was examined from a regiochemical point of view, and despite the small electronic anisotropy of the double bond, electrophilic radicals were found to add preferentially at C(5) with selectivities of up to 5:1. We also report the first case of an inversion of the regioselectivity of a radical reaction using Lewis acids.
D‐Gluconhydroximo‐1,5‐lactam and Related N‐Arylcarbamates Theoretical Calculations, Structure, Synthesis, and Inhibitory Effect on β‐Glucosidases
Authors: Hoos Roland , Naughton Andrew B. , Thiel Walter , Vasella Andrea , Weber Wolfgang , Rupitz Karen , Withers Stephen G. 
Published: December 2004

AbstractThe known D‐gluconhydroximo‐1,5‐lactam (= D‐glucono‐1,5‐lactam oxime) 7a, its nitrogen isotopomers 7b and 7c, and the N‐arylcarbamates 26–29 were synthesized from 2,3,4,6‐tetra‐O‐benzyl‐D‐glucono‐1,5‐lactam (11a) and its nitrogen isotopomer 11b to establish the controversial structure of 7a and to study the inhibition of β‐glucosidases by the N‐arylcarbamates 26–29. Conversion of 11a with Lawesson's reagent yielded a mixture of the thionolactam 15a and its manno‐configurated isomer 16a, which was transformed into a mixture of the benzylated hydroximo‐lactam 13a and the manno‐isomer 17a. Debenzylation (Na/NH3) and acetylation of this mixture led to the gluco‐configurated pentaacetate 14a and the manno‐isomer 18a. Treatment of 11a with Et3O·BF4 and then with H2NOH gave exclusively the benzylated D‐gluconhydroximo‐1,5‐lactam (benzylated D‐nojirilactam oxime) 13a, which was transformed into 14a. Deacetylation of 14a yielded the hydroximo‐lactam 7a. The isotopomers 7b and 7c were obtained by analogous reaction sequences, using either 15NH3 or 15NH2OHHCl. To prepare the acetylated N‐arylcarbamates 20–25, 13a was debenzylated and acetylated (→ 14a), followed by selective deacetylation to the tetraacetate 19a and treatment with the appropriate isocyanates. The structure of the 2‐chlorophenyl carbamate 21 was established by X‐ray analysis. Deacetylation of 20–23 led to the N‐arylcarbamates 26–29.The 15N‐NMR spectra of 7b, 7c, and of their precursors 13b, 13c, 14b, and 14c, show that the CN bond in all these lactam oximes is exocyclic as predicted from semiempirical and ab initio SCF‐MO calculations on the structure of acetamide oxime and 5‐pentanelactam oxime. According to these calculations, 5‐pentanelactam oxime is a (Z)‐configurated, flattened chair. X‐ray analysis established the structure of D‐glucono‐1,5‐lactam oxime (7a) in the solid state, where it adopts a conformation between 4C1 and 4H3. In H2O, 7a is a flattened 4C1. The calculations also predict that protonation at the exocyclic N‐atom strengthens the conjugation between the endocyclic N‐atom and the hydroxyimino group, and leads to a half‐chair conformation. This is evidenced by the chemical shift differences in the 15N‐NMR spectra observed upon protonation of 7b and 7c. The hydroximolactam 7a and the N‐arylcarbamates 26–29 are competitive inhibitors of the β‐glucosidases from sweet almond (emulsin) and from Agrobacterium faecalis (= Abg), with KI values between 8 and 21·10−6M against emulsin (at pH 6.8) and between 0.15 and 1.2·10−6M against Abg (at pH 7.0).
A New Approach to 5‐Thiosugars: 5‐Thio‐D‐Gluconhydroximo‐1,5‐lactone, Synthesis and Evaluation as β‐Glucosidase Inhibitor
Authors: Ermert Philipp , Vasella Andrea 
Published: December 2004

AbstractThe thiolactone oxime 10 was synthesized in ten steps from the known tri‐O‐benzylglucose 13, which was transformed into the oxime 14, silylated (→ 15), and mesylated (→ 16). Treatment of 16 with Bu4NF yielded the L‐ido‐epoxide 17 and the hydroxylamine 18; the isomeric D‐gluco‐configurated hydroxylamine 20 was prepared from 17. Reaction of 17 with thiourea yielded the thiirane 19. Ring opening was best effected with HBr (→ 22·HBr). The N‐glycosylhydroxylamine 22 was immediately oxidized to 24, as it reverted to 19. Similarly, 19 was transformed into the chlorides 21 and 23. The iodide 25 reacted with TEMPO to afford 29 besides 26 and 30; nucleophilic substitution of 23, 24, or 25 gave unsatisfactory yields of 26 or 27, and 28. Birch reduction transformed 29 into 10 which was isolated via the pentaacetate 32, which was also transformed into the tetraacetate 33. The weak activity of 10 as an inhibitor of sweet‐almond and Agrobacter β‐glucosidase is in keeping with categorization of the lactone and lactam oximes 1–5 and the 5‐thiosugars 6–9 as transition‐state and substrate analogs, respectively.
Chemo‐enzymatic Synthesis of 6″‐O‐(3‐Arylprop‐2‐enoyl) Derivatives of the Flavonol Glucoside Isoquercitrin
Authors: Danieli Bruno , Bertario Andrea , Carrea Giacomo , Redigolo Barbara , Secundo Francesco , Riva Sergio 
Published: December 2004

AbstractA chemo‐enzymatic approach to some 6″‐O‐(3‐arylprop‐2‐enoyl) derivatives of the flavonol glucoside isoquercitrin (2a) was explored to overcome the inability to directly introduce these acyl moieties by an enzyme‐catalyzed reaction of 2a with the corresponding activated esters. This new approach was based on the regioselective introduction of a methyl malonate residue at the CH2OH of the sugar moiety by catalysis with the protease subtilisin (→ 22a). The mixed diester 22a was then subjected to chemoselective hydrolysis of the methoxycarbonyl function by another enzyme, biophine esterase (→ 23). Finally, the malonic monoester 23 was reacted in a Knoevenagel‐type condensation with benzaldehyde, 4‐hydroxybenzaldehyde, or 4‐hydroxy‐3‐methoxybenzaldehyde to afford the target 6″‐O‐(3‐arylprop‐2‐enoyl) isoquercitrins 2b–d.
Nucleotides. Part XLII. The 2‐dansylethoxycarbonyl (= 2‐{[5‐(dimethylamino)naphthalen‐1‐yl]sulfonyl}ethoxycarbonyl; dnseoc) group for protection of the 5′‐hydroxy function in oligoribonucleotide synthesis
Authors: Bergmann Frank , Pfleiderer Wolfgang 
Published: December 2004

AbstractThe 2‐dansylethoxycarbonyl (Dnseoc) group was employed for protection of the 5′‐hydroxy function in oligoribonucleotide synthesis by the phosphoramidite approach using the acid‐labile tetrahydro‐4‐methoxy‐2H‐pyran‐4‐yl (Thmp) group for 2′‐protection. The syntheses of monomeric building blocks, both phosphoramidites and nucleoside‐functionalized supports, are described for the four common nucleosides adenosine, guanosine, cytidine, and uridine, and for the two modified minor nucleosides ribothymidine (= ribosylthymine) and pseudouridine.
Oligosaccharides Related to Tumor‐Associated Antigens. Part I. Synthesis of the propyl glycoside of the trisaccharide α‐L‐Fucp‐(1 → 2)‐β‐D‐Galp‐(1 → 3)‐β‐D‐GalpNAc, component of a tumor antigen recognized by the antibody MBr1
Authors: Lay Luigi , Nicotra Francesco , Panza Luigi , Russo Giovanni , Adobati Elena 
Published: December 2004

AbstractThe synthesis of the trisaccharide α‐L‐Fucp‐(1 → 2)‐β‐D‐Galp‐(1 → 3)‐β‐D‐GalpNAc‐1‐OPr (2) is described. The N‐acetylgalactosamine 6 was obtained from 4 by an intramolecular displacement of a (trifluoromethyl)sulfonyloxy by a pivaloyloxy group with its concomitant migration from position 3 to position 4 (Scheme 1). The galactosyl donor 9 was obtained from 7 via 8 by regioselective opening of the orthoester function with AcOH/pyridine followed by treatment with CCl3CN and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) (Scheme 2). Glycosylation of 6 with 9 in the presence of BF3 · OEt2 gave the disaccharide 10. Selective deprotection of 10 at OC(2′) followed by glycosylation with 12 and by standard deprotection afforded the title trisaccharide 2 (Scheme 3). Preliminary biological testing showed that 2 is able to inhibit the binding of the monoclonal antibody MBrl to the target tumor cells MCF7 in a dose‐dependent manner.
Diastereo‐ and Enantiocontrolled Synthesis of (–)‐Allosedamine via Cycloaddition of a Chiral Nitrone
Authors: Oppolzer Wolfgang , Deerberg Jörg , Tamura Osamu 
Published: December 2004

AbstractThe piperidine alkaloid (–)‐allosedamine (1) has been synthesized, in 21% overall yield, in nine steps starting from the formyl‐ester 4. The synthesis features the reaction cascade 7 → 3 → 2, involving asymmetric electrophilic enolate hydroxyamination, hydroxylamine/aldehyde condensation, and nitrone/styrene cycloaddition, as well as the reductive N/O cleavage‐decyanation 12 → 1.
Glycosylidene Carbenes. Part 16. Glycosidation of methyl 6‐O‐trityl‐α‐D‐altropyranoside
Authors: Bozó Eva , Vasella Andrea 
Published: December 2004

AbstractHydrogen bonding of the triol 4 in chlorinated solvents was studied by IR (CH2Cl2 and CCl4) and 1H‐NMR spectroscopy (CDCl3), and the regioselectivity of the glycosidation of the triol 4 by the diazirine 1 is predicted on the basis of two assumptions: preferred protonation of the intermediate glycosylidene carbene by the OH group involved in the weakest intramolecular H‐bond, and attack in the π‐plane of the thereby generated oxycarbenium cation either by the reoriented oxy anion, or by a properly oriented vicinal OH group. Glycosidation led to the disaccharides 5–10 (Scheme) which were separated and characterized as their acetates 11–16, to the lactone azines 17 and to the 2‐(benzyloxy)glucal 18. In agreement with the predictions, glycosidation in non‐coordinating solvents gave the 1,2‐, 1,3‐, and 1,4‐linked disaccharides in decreasing relative amounts. Glycosidation in THF proceeded with a lower degree of regioselectivity and led preferentially to the β ‐D‐anomers, except for the minor, 1,4‐linked disaccharides, where THF had only a weak influence on stereoselectivity at room temperature and led to a slight increase of the α ‐D‐anomer at −80°.
A Novel Rearrangement Product of Podophyllotoxone – Ester Derivatives and in vitro cytotoxicity studies
Authors: Höfert Peter H. , Matusch Rudolf 
Published: December 2004

AbstractA new rearrangement product of podophyllotoxone was obtained by reaction with strong bases. In vitro cytotoxities of this substance and some derivatives were determined using L‐1210 and KB cell lines.
Asymmetric Synthesis of 3‐Hydroxyprolines by Photocyclization of N‐(2‐Benzoylethyl)glycinamides
Authors: Wessig Pablo , Wettstein Philipp , Giese Bernd , Neuburger Markus , Zehnder Margaretha 
Published: December 2004

AbstractThe chiral N‐(2‐benzoylethyl)‐N‐tosylglycinamides 1a‐c were prepared from the C2‐symmetric pyrrolidines 5a‐c. Irradiation of these ketones 1a‐c gave cis‐3‐hydroxyprolinamides 10‐12 in moderate to good yields (Scheme 3). The de of the photocyclizations depended on the size of the substituents in positions C(2) and C(5) of the chiral pyrrolidine auxiliaries. In addition, the de varied with the reaction temperature, allowing the determination of activation‐parameter differences. The structure of products 10‐12 were established by NMR and X‐ray analyses.
Oxidative Coupling of αω,‐Di(cyclopentadienyl)alkane‐diides
Authors: You Shaochun , Gubler Matthias , Neuenschwander Markus 
Published: December 2004

AbstractThe CuII‐induced oxidative coupling of αω,‐di(cyclopentadienyl)alkane‐diides 6 (n = 2–5) has been shown to proceed mainly by an intermolecular pathway to give polymers 8, while the yield of intramolecular coupling 6 → 7 strongly decreases with increasing number n of C‐atoms of the alkyl chain (Scheme 3). For n = 2, intramolecular coupling may be considerably enhanced by replacing the H‐atoms of the CH2CH2 bridge of 6a (n = 2) by Me groups. In this case, intramolecular couplings 11 → 20 (Scheme 7) and 22 → 23 + 24 (Scheme 8) are accomplished with a total yield of 59% and 54%, respectively. All the intramolecular couplings investigated so far proceed stereoselectively to give the C2‐symmetrical cyclohexanes 7a, 20 and 23 with a fixed chair conformation. These results are easily explained, if a conformational equilibrium E ⇄ F is operative in which large substituents R are assumed to enhance the gauche‐conformation F which is the favored conformation for intramolecular couplings. Bridged dihydropentafulvalenes 20 and 23 are quantitatively rearranged to the thermodynamically favored bridged pentafulvenes 27 and 28 under base or acid catalysis, respectively (Scheme 9).
Solution Structure of One‐Electron Reduced and Oxidized Molecules with Twisted Donor and Acceptor Moieties
Authors: Hopf Henning , Kreutzer Martin , Mlynek Cornelia , Scholz Markus , Gescheidt Georg 
Published: December 2004

AbstractThe solution structures of the radical anion and the radical cation of the donor‐acceptor molecules 3,4‐di(1,3‐dithiol‐2‐ylidene)‐4‐phenylbut‐1‐ene‐1,1‐dicarbonitrile (1) and 3,4‐di(1,3‐dithiol‐2‐ylidene)‐4‐phenylbut‐1‐ene‐1,1,2‐tricarbonitrile (2) are discussed based on cyclovoltammetric and ESR/ENDOR measurements. It is shown that the spin population of the radical anions is limited to the di‐ and tricyanoethene moiety and the coplanar 1,3‐dithiole at C(3), whereas that of the radical cations resides mainly inside the two 1,3‐dithiole rings. The energies of the long‐wave bands in the electronic‐absorption spectra of 1 and 2 correspond to the differences between the oxidation and reduction potentials and thus point to a charge‐transfer character of these transitions.
Hoogsteen‐Duplex DNA: Synthesis and base pairing of oligonucleotides containing 1‐deaza‐2′‐deoxyadenosine
Authors: Seela Frank , Wenzel Thomas 
Published: December 2004

AbstractOligodeoxyribonucleotides containing 1‐deaza‐2′‐deoxyadenosine ( = 7‐amino‐3‐(2‐deoxy‐β‐D‐erythro‐pentofuranosyl)‐3H‐imidazo[4, 5‐b]pyridine; 1b) form Hoogsteen duplexes. Watson‐Crick base pairs cannot be built up due to the absence of N(1). For these studies, oligonucleotide building blocks – the phosphonate 3a and the phosphoramidite 3b – were prepared from 1b via 4a and 5, as well as the Fractosil‐linked 6b, and used in solid‐phase synthesis. The applicability of various N‐protecting groups (see 4a–c) was also studied. The Hoogsteen duplex d[(c1A)20] · d(T20) (11 · 13; Tm 15°) is less stable than d(A20) · d(T20) (12 · 13; Tm 60°). The block oligomers d([c1A)10–;T10] (14) and d[T10–(c1A)10] (15) containing purine and pyrimidine bases in the same strand are also able to form duplexes with each other. The chain polarity was found to be parallel.
Synthesis and Biological Evaluation of 14‐Alkoxymorphinans. Part 10. 14‐O‐Methyl derivatives of 5‐methylnaltrexone and 5‐methylnaloxone
Authors: Schmidhammer Helmut , Nussbaumer Christine , Patel Dinesh , Traynor John R. 
Published: December 2004

AbstractIn several steps, 5, 14‐O‐dimethylnaltrexone (3) and 5, 14‐O‐dimethylnaloxone (4) were prepared starting from 5, 14‐O‐dimethyloxycodone (5). Compound 3 exhibited opioid agonism in vitro (guinea‐pig ileum and mouse vas deferens preparations) and antagonism in vivo (AcOH‐writhing test in mice), while compound 4 was found to be an agonist in vitro and in vivo.