bluuebunny/crossref_metadata_2025 huggingface dataset:
Steric Effects on Reaction Rates. Part XII. Force‐Field Calculations for the Solvolysis of Cyclobutyl and Tricyclyl Derivatives
Authors: Müller Paul , Milin Didier
Published: December 2004

Force‐field parameters have been developed for the molecular‐mechanics calculation of tertiary carbenium ions with tricyclane structure, for tertiary cyclobutyl and cubyl cations. The cyclobutyl parameters are also applicable to tertiary 7‐norbornyl cations. Satisfactory plots are obtained for correlation of the rates of solvolysis with the differences in steric energies between carbenium ions and the corresponding bromides.
Helicity Induction in Helicate Self‐Organisation from Chiral Tris(bipyridine) Ligand Strands
Authors: Zarges Wolfgang , Hall Jonathan , Lehn Jean‐Marie , Bolm Carsten
Published: December 2004

The chiral tris, and pentakis(bipyridine) ligand strands 3a and 4 were synthesised, each in optically pure form with (S,S)‐configuration. Ligand 3a yielded substituted double‐helical metal complexes, derived from the parent trihelicate structure 2, with CuI and AgI ions. The spectral data, in particular the 1H‐NMR spectra and the large positive Cotton effect, indicate that helicate formation occurs with very high induction of helicity. Together with consideration of the steric effects in the two possible helical diastereoisomers (P)‐1 and (M)‐1 that may be formed, the data favour the preferential generation of the right‐handed double helicate (P)‐1 from the tris(bipyridine) strand 3a of(S,S)‐configuration.
Stereoselective Hydrolysis of Substituted Cyclopropanedicarboxylates with Pig Liver Esterase
Authors: Walser Paula , Renold Peter , N'Goka Victor , Hosseinzadeh Fatemeh , Tamm Christoph
Published: December 2004

The hydrolysis of the meso‐cyclopropane‐1,2‐dicarboxylates 1a‐3a, 4, 5a, 6a, and 9, containing various substituents at C(3), and of the rac‐3‐phenylcyclopropane‐1,2‐dicarboxylates7a, 8a, and 10 with pig liver esterase (PLE) is described. The stereoselectivtty and absolute configurations of the products were determined. An interpretation of results was attempted on the basis of a recent active‐site model for PLE.
Energy Transfer within Oligonucleotides from a Lumazine (= Pteridine‐2,4(1H,3H)‐dione) Chromophore to Bathophenanthroline‐ruthenium(II) Complexes
Authors: Bannwarth Willi , Pfleiderer Wolfgang , Müller Francis
Published: December 2004

The chemical insertion of 1‐(2′‐deoxy‐β‐D‐ribofuranosyl)‐6,7‐dimethyllumazine (1) and of a bathophenan‐throline‐ruthenium(II) complex into synthetic oligodeoxynucleotides is described. This combination represents a new energy‐transfer system with the lumazine chromophore as donor and the Ru complex as acceptor within the nucleotide. The system can be measured by time‐resolved fluorometry or by lifetime measurements of the lumazine fluorescence and bears the potential of a spectroscopic ruler.
Synthesis of N,N‐Disubstituted Lactone Hydrazones via (Sulfonylimino)‐ethers
Authors: Fritschi Stephan , Vasella Andrea
Published: December 2004

The dihydropyran 3 reacts with sulfonyl azides to give the known (sulfonylimino)‐ethers ( = lactone sul‐fonylimines) 4 and 18. Reaction of 4 with NH2NH2 · H2O leads to the aminoiriazole‐dibulanol 5, characterized as its tetraacetate 8, and not, as previously claimed, to 6 or 7. Similarly, the dihydrofuran‐derived (tosylimino)‐ether 10 yields 11 The structure of 5 was established by X‐ray analysis, and a mechanism for its formation is proposed. Reaction of 4 with NH2NMe2 afforded the lactone hydrazone 16 and the hydrazidine 17. Catalysis by imidazole suppressed the formation of 17similarly, the [(trifluoromethyl)sulfonyl]imine 18 yielded 16, and, by reaction with NH2N(Me)Ph or 4‐amino‐4H‐1,2,4‐triazole, the lactone hydrazone 19 and the adduct 20, respectively. The 1,4‐lactone hydrazone 21 was obtained from 10 or from 22. The structure of 20 was established by X‐ray analysis. Treatment of 16 with BuLi followed by BnBr yielded the α‐alkylated lactone hydrazone 23.
Radical Cations and Radical Anions of Three Bridgehead Azopolycycloalkanes: A Fluid‐Solution ESR Study
Authors: Gescheidt Georg , Lamprecht Axel , Rüchardt Christoph , Schmittel Michael
Published: December 2004

The radical mono‐ions of three azoalkanes in which the azo group is connected to the polycyclic alkane moieties at the bridgehead C‐atoms, i. e. 1,1′‐azonorbornane (1), 1,1′‐azotwistane (2), and 1,1′‐azobi‐cyclo[3.2.1]octane (3), were studied in fluid solution by ESR spectroscopy. According to the ESR parameters and MO models, the radical cations of 1–3 should be considered as σ radicals, whereas the corresponding radical anions are π radicals. INDO calculations point to a remarkable dependence of the l4N‐coupling constants on the geometry at the N‐atoms in the radical cations of aliphatic azo compounds.
A Highly Convergent Total Synthesis of (+)‐Myxovirescine M2. Preliminary Communication
Authors: Seebach Dieter , Maestro Miguel A. , Sefkow Michael , Neidlein Axel , Sternleld Francine , Adam Geo , Sommerfeld Thimo
Published: December 2004

The antibiotic myxovirescine M2was synthesized from seven building blocks (1–7,Scheme 1), with the following chiral starting materials being employed: (S)‐malic acid, (+)‐D‐ribonolactone, (S)‐2‐(hydroxymethyl)butanoate, and (2R,4S)‐5‐hydroxy‐2,4‐dimethylpenLanoate. Three new nucleophilic reagents,8–10, for C‐C bond formation have been used. The key steps of the synthesis are: aSuzukicoupling between an alkyl borane and a vinyl bromide (4+12e→13), aJuliaolefinalion (14+17→18), and aYamaguchimacrolactonizalion to form the 28‐membered lactone (18→19), This extremely convergenl synthetic approach will allow the preparation of a number of the 31 known myxovirescine molecules.
Chiral Tetraamines Based on (S)‐2‐(Aminomethyl)pyrrolidine: Template synthesis and properties of copper(II) complexes
Authors: Bernhardt Paul V. , Comba Peter , Hambley Trevor W. , Martin Lisandra L. , Várnagy Katalin , Zipper Luc
Published: December 2004

The template reaction of {bis[(S)‐2‐(aminomethyl)pyrrolidine]}copper(II) with formaldehyde, nitroethane, and base in MeOH yields optically pure {1,7‐bis[(S)‐pyrrolidin‐2‐yl]‐4‐methyl‐4‐nitro‐2,6‐diazaheptane}‐ copper(II) ([Cu((S,S)‐mnppm)]2+) in high yield. The same reaction with rac‐2‐(aminomethyl)pyrrolidine is also described. Preparative details and spectroscopic and electrochemical properties of the CuII complexes and of the free ligands are reported and compared with structural, spectroscopic and electrochemical data of the CuII complex of the unsubstituted parent ligand 1,7‐bis[(S)‐pyrrolidin‐2‐yl]‐2,6‐diazaheptane (ppm). The crystal structure of [Cu(ppm)]Cl ClO4 has been determined by X‐ray diffraction methods.
X‐Ray Crystal Structure of 25‐O‐Deacetyl‐27, 28‐didehydro‐27‐demthoxy‐11‐deoxo‐11, 29‐epoxy‐28,29‐dihydro‐21,23‐O‐isopropylidenerifamycin S
Authors: Bartolucci Cecillia , Cellai Luciano , Cerrini Silvio , Di Filippo Patrizia , Lamba Doriano
Published: December 2004

In search of new types of semisynthetic derivatives of the natural antibiotic rifamycin S (1), we synthesized 25‐O‐deacetyl‐27,28‐didehydro‐27‐demethoxy‐11‐deoxo‐11,29‐epoxy‐28, 29‐dihydro‐21,23‐O‐isopropyli‐denerifamycin S (3). Its X‐ray crystal structure shows a new type of ansa‐chain with an 11,29‐epoxy moiety, the loss of the MeO group on C(27), and the shift of the CC bond from C(28),C(29) to C(27),C(28). These modifications result in a conformational rearrangement of the whole ansa‐chain, nonetheless the overall spatial shape of the molecule is still close to that of most rifamycins. As found in other 11‐deoxo‐11‐hydroxyrifamycin‐S derivatives, the chromophore rings of 3 give rise to π‐π association in the crystal.
Diastereoselective Spirocyclization of Imines of 2‐Substituted 1H‐Indole‐3‐ethylamines ( = Trypatamines): Variation of the electrophile and the substituent at C(2) and its influence on the steric outcome. 6th Communication on indoles, indolenines, and indolines
Authors: Freund Ralf , Martinović Suzanna , Bernauer Karl
Published: December 2004

Tryptimines of type 7 form with various acyl halogenides EX preferentially tricycles of type 8 (cf: Scheme 2). The homochiral imines 9 and 17 are transformed into (2′R,3S)‐configurated products. The synthetic and mechanistic importance of these results is discussed.
Fluctuating Double‐Bond Localization and Charge Migration in π Systems
Authors: Heilbronner Edgar , Shaik Sason
Published: December 2004

In π systems with localized double bonds, the switch from one localization pattern to another symmetry‐equivalent one, and the corresponding changes in electron distribution are often considered to proceed via a delocalized transition state of higher symmetry. We present a different mechanism, according to which the double‐bond localization and the concomitant charge distributions can fluctuate without change in energy and without passing through a delocalized, higher‐symmetry transition state. This result is obtained within a simple, independent‐electron (HMO‐type) treatment.
Unusual and Novel C11H16 Hydrocarbons from the Southern Australian Brown Alga Dictyopteris acrostichoides (Phaeophyceae)
Authors: Wirth Dieter , Fischer‐Lui Iris , Boland Wilhelm , Icheln Detlef , Runge Thorsten , König Wilfried A. , Phillips Julie , Clayton Margaret
Published: December 2004

Unusual and novel C11H16 olefins with (E)‐ or (E,E)‐configuration instead of the previously known (Z)‐ or (E,Z)‐configuration at the double bond(s) within the longer side chain are the main products of the Australian phaeophyte Dictyopteris acrostichoides. This configuration anomaly refers to all four series of alicyclic C11H16 hydrocarbons, namely the disubstituted cyclopentenes and cyclopropanes, as well as the monosubstituted cycloheptadienes and cyclopentenes. Chiral compounds within the above series have the same absolute configuration. The two (cyclopent‐3‐enyl)hexa‐1, 3‐dienes 11 and 13 are found for the first time. The absolute configuration and optical purity of the hydrocarbons are determined by gas chromatography on modified cyclodextrins as chiral stationary phases. The synthesis of chiral references via lipase‐catalyzed resolutions is described.
Homolytic Substitution Reaction at a Silicon Atom
Authors: Kulicke Klaus. , Chatgilialoglu Chryss Stomos , Kopping Birgit , Iese Bernd
Published: December 2004

Tris(trimethylsilyl)silane (2) is an efficient hydrosilylating agent of 1,6‐dienes 1 operating via a free‐radical chain mechanism. The intermediate alkyl radical 3 attacks the second olefinic bond of the diene 1 and forms cyclopentylalkyl radical 4. Using a low concentration of the hydrogen donor 2, a radical substitution reaction at the Si‐center of cis‐4 occurs and yields the bicyclic silane 6. The rate of this homolytic substitution at the Si‐atom is 2.4 · 105 s‐1 (80°).
Synthesis of N‐Acetylallosamine‐Derived Disaccharides
Authors: Maloisel Jean‐Luc , Vasella Andrea
Published: December 2004

The protected disaccharide 44, a precursor for the synthesis of allosamidin, was prepared from the glycosyl acceptor 8 and the donors 26–28, best yields being obtained with the trichloroacetimidate 28 (Scheme 6). Glycosidation of 8 or of 32 by the triacetylated, less reactive donors 38–40 gave the disaccharides 46 and 45, respectively, in lower yields (Scheme 7). Regioselective glycosidation of the diol 35 by the donors 38–40 gave 42, the axial, intramolecularly H‐bonded OHC(3) group reacting exclusively (Scheme 5). The glycosyl acceptor 8 was prepared from 9 by reductive opening of the dioxolane ring (Scheme 3). The donors 26–28 were prepared from the same precursor 9 via the hemiacetal 25. To obtain 9, the known 10 was de‐N‐acetylated (→ 18), treated with phthalic anhydride (→ 19), and benzylated, leading to 9 and 23 (Schemes 2 and 3). Saponification of 23, followed by acetylation also gave 9. Depending upon the conditions, acetylation of 19 yielded a mixture of 20 and 21 or exclusively 20. Deacetylation of 20 led to the hydroxyphthalamide 22. De‐N‐acetylation of the 3‐O‐benzylated β‐D‐glycosides 11 and 15, which were both obtained from 10, was very sluggish and accompanied by partial reduction of the O‐allyl to an O‐propyl group (Scheme 2). The β‐D‐glycoside 30 behaved very similarly to 11 and 15. Reductive ring opening of 31, derived from 29, yielded the 3‐O‐acetylated acceptor 32, while the analogous reaction of the β‐D‐anomer 20 was accompanied by a rapid 3‐O→4‐O acyl migration (→34; Scheme 4). Reductive ring opening of 21 gave the diol 35. The triacetylated donors 38–40 were obtained from 20 by debenzylidenation, acetylation (→36), and deallylation (→37), followed by either acetylation (→38), treatment with Me3SiSEt (→39), or Cl3CCN (→ 40).
Synthesis of Allosamidin
Authors: Maloisel Jean‐Luc , Vasella Andrea , Trost Barry M. , Van Vranken David L.
Published: December 2004

The previously prepared disaccharide 2 was deprotected (→3) and transformed into the trichloroacetimidate 4. In the presence of Me3SiOTf, 4 reacted regioselectively with the racemic allosamizoline benzyl ether 5, to yield (61%) the pseudotrisaccharides 7–10 (44:40:9:7) and the elimination product 6 (Scheme 1). Selective dephthaloylation (MeNH2, MeOH) of 7 and 8, followed by acetylation, gave 12 (73%) and 13 (74%), respectively (Scheme 2); harsher conditions (NH2NH2.H2O, EtOH, reflux), followed by acetylation, transformed 7 into 11. Deacetylation of 11–13 yielded 14–16, respectively. Allosamidin (1) was obtained in high yield by hydrogenation of 15 under acidic conditions (Scheme 3). Similarly, 16 and 14 were transformed into 17 and 18, respectively. Preliminary data on the inhibition of endochitinases by 1 and 17 are reported.
Tetrahydrolipstatin: Degradation products produced by human carboxyl‐ester lipase
Authors: Stalder Henri , Oesterhelt Gottfried , Borgström Bengt
Published: December 2004

The fate of tetrahydrolipstatin (1) incubated with human carboxyl‐ester lipase (HCEL) was investigated. The primary metabolite was identified as δ‐(N‐formyl‐L‐leucyloxy)‐β‐hydroxy acid 2a with conserved configuration. It is formed by attack of the active‐site serine of HCEL at the carbonyl C‐atom of the β‐lactone ring of 1 followed by hydrolysis of the intermediate serine ester. Further products isolated were identified and a complete degradation scheme is proposed.
Setting the Bridgehead Oxidation Level in trans‐Tricyclo[9.3.1.03,8]pentadecanes as a Prelude to the Dual Synthesis of Taxol and Taxusin
Authors: Paquette Leo A. , Combrink Keith D. , Elmore Steven W. , Zhao Mangzhu
Published: December 2004

The key elements associated with the synthetic elaboration of functionalized trans‐tricyclo‐[9.3.1.03,8]pentadecanes carrying either a bridgehead H or OH substituent are detailed. Starting with 12, a ketone available in two steps from (R)‐2‐oxo‐7,7‐dimethyl‐l‐vinylbicyclo[2.2.1]heptane, it proved possible to introduce trans‐B/C ring juncture configuration as in 16 in five steps. This advanced intermediate constitutes the point of bifurcation. The pathway to taxusin precursor 23 was attained by stereospecific osmylation, reduction, and pinacol‐like 1,2‐Wagner‐Meerwein rearrangement within acetoxy mesylate 22c. Still more abbreviated is the route to 32, which again takes advantage of the osmylation step but proceeds, forward without reduction of the rear carbonyl group. Once hydroxy diketone 31 is produced, equilibration in the presence of (t‐BuO)3Al results in complete conversion to 32. The many stereoselective transformations developed in the course of this study, in combination with the several thermodynamic questions that have been clarified, are expected to be highly serviceable as more advanced thrusts toward taxusin and taxol are mounted.
Reaction of Diphenyl Phosphorochloridate with Amide Enolates: A new and convenient synthesis of 2‐monosubstituted 3‐(n‐methyl‐n ‐phenylamino)‐2H‐azirines
Authors: Villalgordo José M. , Heimgartner Heinz
Published: December 2004

Reaction of diphenyl phosphorochloridate with amide enolates and subsequent treatment with NaN3 leads to 2‐monosubstituted 3‐amino‐2H ‐azirines 5 in moderate yields. The reactivity of these azirines is briefly explored.
Carbonyliron Complexation and Carbonyl Insertion of Allenic Ketones
Authors: Trifonov Latchezar S. , Orahovats Alexander S. , Linden Anthony , Heimgartner Heinz
Published: December 2004

The allenic α‐ketones 5a–f give, on irradiation in the presence of [Fe(CO)5], the bis(tricarbonyliron) complexes 6a–f. In the case of ketone 5e, a minor bis(tricarbonyliron) complex with the proposed unique structure 8 is also obtained. Ketones 5a–d, which are disubstituted at C(4), under the same conditions, afford also the lactones 7a–d in moderate yields. The latter reaction is a new carbonyliron‐mediated carbonyl insertion. The structure of the binuclear complexes 1a and 6e were established by X‐ray crystallography.
Säurekatalysierte Umsetzungen von 2‐ Vinylanilin‐Derivaten mit 1‐Benzyl‐ und 1‐Methylpiperidin‐4‐on: Eine Elegante Synthese Neuer Polycyclischer Indol‐Derivate
Authors: Walter Harald , Sauter Hanspeter , Schneider Josef
Published: December 2004

Acid‐Catalyzed Reactions of 2‐Vinylaniline Derivatives with 1‐Benzyl‐ and 1‐Methylpiperidin‐4‐one: An Elegant Synthesis of New Polycyclic Indole Derivatives

The reaction of 2‐vinylaniline derivatives with 1‐benzylpiperidin‐4‐one or 1‐methylpiperidin‐4‐one in toluene at temperatures between 115 and 120° with toluene‐4‐sulfonic acid as catalyst leads in good yields to a new class of polycyclic indole derivatives (Scheme 1, Table 1). The structure of the new diastereoisomerically pure racemic compounds 1–5 is determined by NMR‐spectroscopic methods. A reaction mechanism proceeding via cyclization of enamine 9, leading to a racemic, tricyclic reactive intermediate 10, and subsequent intramolecular 1,5‐dipolar cyclization as key steps in proposed for the formation of octahydropyrido[4′,3′:4]cyclobut[1,2‐b]indoles 1–5. The scope and limitations of the new method are discussed (see Table 2).
Radical Rearrangements of 2‐O‐(Diphenoxyphosphoryl)glycosyl Bromides
Authors: Koch Andreass , Giese Bernd
Published: December 2004

A variety of 2‐deoxy‐1‐O‐diphenoxylphosphoryl‐hexopyranoses were generated in situ by a radical 2→1 migration of the phosphate group. The structures of the reactive rearrangement products were fully elucidated by NMR spectroscopy. Rate constants for this new rearrangement were determined fro a variety of substrates.
Synthesis and Antiviral Activity of Novel Adamantylpeptides
Authors: Vranešić Branka , Tomašić Jelka , Smerdel Stainslav , Kantoci Darko , Benedetti Fabio
Published: December 2004

A novel type of compound that contains a peptide specific for bacterial peptidoglycans (immunomodulatory activity) and an adamantyl residue (antiviral activity) was synthesized. Thus, L‐Ala‐D‐γGln was linked to DL‐Gly(Ada) yielding two diasteroisomers 3a and 3b, i.e. ambo‐Gly(Ada)‐L‐Ala‐D‐γGln (γGln = isoglutamine‐4‐amino‐4‐carbamoylbutanoic acid; Ada = adamantyl). The diastereoisomers were easily separated by column chromatography (silica gel) and characterized, but only the use of a stereospecific enzyme led to the assignment of the configuration of the Gly(Ada) moiety in the two diastereoisomers. The cytotoxic effect and antiviral activity of the novel adamantyltripeptides 3a and 3b, observed as the cell survival and the infectivity reduction of the influenza A virus H1N1 and H3N2 strains, respectively, were studied on MDCK cells in vitro. Both 3a and 3b exhibited low cytotoxicity for MDCK cells and reduced the infectivity of the influenza A virus strains, but to a different extent on different Strain.
Synthesis of Aristotelia‐Type Alkaloids. Part XII. Total synthesis of (−)‐tasmanine. Stereoelectronic factors that control the rearrangement of 3H‐indol‐3‐ol derivatives to oxindoles ( = 1,3‐dihydro‐2H‐indol‐2‐ones) or to pseudoindoxyls ( =1,2‐dihydro‐3H‐indol‐3‐ones)
Authors: Güller Rolf , Borschberg Hans‐Jürg
Published: December 2004

The oxidative transformation of (+)‐aristoteline ((+)‐5) into its metabolites, the recently synthesized indole alkaloids (−)‐serratoline ((−)‐6), (+)‐aristotelone ((+)‐2), and (−)‐alloaristoteline ((−)‐22), was investigated in more detail. It was demonstrated that the diastereoface selectivity of the reaction of (+)‐5 with 3‐chloroperbenzoic acid can be altered by variation of the solvent as well as by addition of CF3COOH. The chemoselectivity of the 1,2‐rearrangement of the intermediate 3H‐indol‐3‐ol derivatives could be controlled as follows: treatment of 3H‐indol‐3‐ols with aqueous polyphosphoric acid led to the pseudoindoxyl ( = 1,2‐dihydro‐3H‐indol‐3‐one) derivatives, whereas an analogous treatment of the corresponding O‐benzoates furnished exclusively the corresponding, constitutionally isomeric 2‐oxindole ( = 1,3‐dihydro‐2H‐indol‐2‐one) products. Exploitation of these and related findings led to efficient total syntheses of the Aristotelia alkaloid (−)‐tasmanine ((−)‐1) and of the corresponding unnatural epimer (+)‐12, as well as of the two pseudoindoxyls (+)‐aristotelone ((+)‐2) and (−)‐2‐epiaristotelone ((−)‐11). All these transformations were carried out with synthetic (+)‐aristoteline ((+)‐5) as the single indole alkaloid precursor.
The Donor‐Acceptor‐Acceptor Purine Analog: Transformation of 5‐aza‐7‐deaza‐1H‐isoguanine (=4‐aminoimidazo‐[1,2‐a]‐1,3,5‐triazin‐2(1H)‐one) to 2′‐deoxy‐5‐aza‐7‐deaza‐isoguanosine using purine nucleoside phosphorylase
Authors: Voegel Johannes J. , Altorfer Michael M. , Benner Steven A.
Published: December 2004

A new synthesis is reported for 4‐aminoimidazo[1,2‐a]‐1,3,5‐triazin‐2(1H)‐one ( =5‐aza‐7‐deaza‐isoguanosine; 8), a purine analog that, when incorporated into an oligonucleotide chain, presents a H‐bond donor‐acceptor‐acceptor pattern to a complementary pyrimidine analog. A protected ribose derivative was coupled to 8 to yield 4‐amino‐8‐(β‐D‐ribofuranosyl)imidazo[1,2‐a]‐1,3,5‐triazin‐2(8H)‐one ( =5‐aza‐7‐deaza‐isoguanosine; 11) after deprotection, Alternatively, direct synthesis of both the ribo derivative 11 and the corresponding deoxyribo derivative 17 as the β‐D‐anomers was achieved using the enzyme purine nucleoside phosphorylase in a one‐pot reaction. This adapts a known synthetic approach to yield a new strategy for obtaining diastereoisomerically pure deoxyribonucleoside analogs on 1‐gram scales.
Muricatetrocins A and B and Gigantetrocin B: Three New Cytotoxic Monotetrahydrofuran‐Ring Acetogenins from Annona muricata
Authors: Rieser Matthew J. , Fang Xing‐Ping , Anderson Jon E. , Miesbauer Laura R. , Smith David L. , McLaughlin Jerry L.
Published: December 2004

Extracts from the seeds of Annona muricata yielded three new Annonaceous acetogenins: muricatetrocin A (= (5S)‐3‐{(2R)‐2‐hydroxy‐9‐{(2R,5S)‐tetrahydro‐5‐[(1S,4S,5S)‐1,4,5‐trihydroxyheptadecyl]furan‐2‐yl}nonyl}‐5‐methylfuran‐2(5H)‐one; 1), muricatetrocin B (= (5S)‐{(2R)‐2‐hydroxy‐9‐{(2S,5S)‐tetrahydro‐5‐[(1S,4S,5S)‐1,4,5‐trihydroxyheptadecyl]furan‐2‐yl}nonyl}‐5‐methylfuran‐2(5H)‐one; 2), and gigantetrocin B (= (5S)‐3‐{(2R)‐2‐hydroxy‐7‐{(2S,5S)‐tetrahydro‐5‐[(1S,4R,5R)‐1,4,5‐trihydroxynonadecyl]furan‐2‐yl}heptyl}‐5‐methyl‐furan‐2(5H)‐one; 3). Their C‐skeletons were deduced by mass spectrometry. Configurations were determined by 1H‐NMR of ketal derivatives and 2D‐NMR experiments utilizing Mosher esters. A previously described compound, gigantetrocin A (= (5S)‐3‐{(2R)‐2‐hydroxy‐7‐{(2S,5S)‐tetrahydro‐5‐[(1S,4S,5S)‐1,4,5‐trihydroxynonadecyl]furan‐2‐yl}heptyl}‐5‐methylfuran‐2‐(5H)one; 4), was also isolated and is new to this species. Compounds 1–4 were all selectively cytotoxic for the HT‐29 human colon‐tumor cell line with potencies at least 10 times that of adriamycin.
Cation Transport across Bulk Liquid Organic Membranes with Oligomers of (R)‐3‐Hydroxybutanoic Acid
Authors: Bürger H. Michael , Seebach Dieter
Published: December 2004

Several oligomeric derivatives 1–5 of (R)‐3‐hydroxybutanoic acid and a cyclic trimer of (R)‐3‐hydroxypentanoic acid (6) were used as ionophores to transport potassium picrate across a bulk liquid CH2Cl2 membrane. Using the cyclic trimer 1 and an oligomer mixture of (R)‐3‐hydroxybutanoic acid, 5 (ca. 28‐mer), for the transport experiments, the alkali‐metal ions from Li+ to Cs+ and the alkaline‐earth‐metal ions from Mg2+ to Ba2+ were also shown to be transported through the organic phase. Although a pronounced enhancement of the transport rates was observed in the presence of 3‐hydroxyalkanoate oligomers, no special selectivity for one ion was detected. The ionophore properties of the investigated oligomers and oligolides derived from 3‐hydroxybutanoic acid are compatible with the alleged role of oligo(3‐hydroxybutanoate) (c‐PHB; ca. 120‐mer) as component of ion channels through cell membranes.
Asymmetric Catalysis by Vitamin B12: The Isomerization of Achiral Aziridines to Optically Active Allylic Amines
Authors: Zhang Zhong Da , Scheffold Rolf
Published: December 2004

Achiral N‐acylaziridines are isomerized to optically active N‐acyl‐allylamines in ee's of up to 95% by catalytic amounts of cob(I)alamin in MeOH.
An Unusual Rearrangement of a Lithiated N‐Acyl‐tetrahydroisoquinoline to an Amino‐indan Skeleton and Structural Comparison of 3‐Amino‐2‐methylindan‐ and ‐tetrahydronaphthalene‐2‐carboxylic Acids as Possible Building Blocks for Peptide‐Turn Mimics
Authors: Gees Thomas , Schweizer W. Bernd , Seebach Dieter
Published: December 2004

Lithium 1‐lithio‐6,7‐dimethoxy‐3‐methyl‐2‐pivaloyl‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylate rearranges to the dilithio derivative of 5,6‐dimethoxy‐2‐methyl‐1‐(pivaloylamino)indan‐2‐carboxylic acid (2, [1,2]‐sigmatropic shift with retention of configuration) by 1,2‐migration resembling the Wittig rearrangement of deprotonated ethers (Scheme 2). The structure, including absolute configuration of the rearrangement product, was determined by X‐ray diffraction. Structural conditions for the rearrangement to occur are tested by subjecting various other tetrahydroisoquinoline derivatives (6, 7, 10, 15) to the metalating conditions. Only one other compound was found to undergo the same rearrangement (15 → 16). Possible mechanisms of the rearrangement are discussed (B–G). Due to the presence of a tetrasubstituted C‐atom, the indan‐type β‐amino‐acid derivative 2 has a conformationally locked structure (NCCCO2R dihedral angle 44°). For comparison, the corresponding tetralin‐type β‐aminoacid derivatives 19–22 were prepared, and it was shown by X‐ray analysis (of the ester 21) that these have larger dihedral angles (ca. 60°). It is proposed that β‐amino acids of the type described here could be incorporated into peptides, providing bents of known angles along the peptide backbone.
HPLC and 1H‐NMR Studies of Alkaline Hydrolysis of Some 7‐(Oxyiminoacyl)cephalosporins
Authors: Vilanova Bartolomé , Muñoz Francisco , Donoso Josefa , Blanco Francisco García
Published: December 2004

Alkaline hydrolysis (pH 10.5) of the three 7‐(oxyiminoacyl)cephalosporins 1a–c (cefuroxime, ceftazidime, and ceftriaxone) was studied at 37° using HPLC and 1H‐NMR techniques. The 7‐epicephalosporin 2, the 3‐methylidene compound 3, and the 6‐epimer 4 of the 3‐methylidene compound 3 were identified for each cephalosporin as the major degradation products under the conditions used; ceftazidime (1b) yielded also the Δ2‐isomer 5b (Scheme 1). A kinetic scheme was developed to account for the production of these compounds, and the different kinetic constants involved in the process were calculated. The experimental results show that the presence of a pyridinio group at position C–C(3) favours the appearance of the Δ2‐isomer, which was detected mainly in cephalosporins bearing an ester function at C(4). The presence of an oxyimino group at CCONHC(7) facilitates epimerization at C(7) (→ 2), whereas that of an electron‐withdrawing group at CC(3) results in a increased formation constant for the 3‐methylidene compound 3. The 3‐methylidene compounds 3a–c produced by the three cephalosporins on cleavage of the β‐lactam ring all underwent epimerization at C(6) to yield the corresponding 6‐epimer 4.
Lanthanide‐Ion Complexation by D‐Glucuronic and D‐Galacturonic Acids
Authors: Fuks Leon , Bünzli Jean‐Claude G.
Published: December 2004

To assess the potential of naturally occurring substances in the treatment of heavy‐metal intoxication, the interaction between D‐galacturonic and D‐glucuronic acids with several trivalent lanthanide ions has been studied in aqueous solutions by means of a spectrophotometric method (27°; 0.1M NaClO4; pH 4.0). Values for the overall stability constants for [LnL] and [LnL2] (Ln = La, Ce, Pr, Nd, Gd, or Lu) complexes are presented and discussed. The interpretation of the data shows that, similarly to acetates, the COOH group coordinates metal ions in both [LnL] and [LnL2] complexes. The 1:1 complexation is supplemented by the ring C(5)O‐atom. Moreover, the C(4)O‐atom seems to play an important role in the steric hindrance of the chelating ligand molecules.
Enantioselective synthesis of (−)‐conduramine C1 and aminobromocyclitol derivatives
Authors: Allemann Susy , Vogel Pierre
Published: December 2004

(1S,2R,6R,7R)‐4‐Phenyl‐3,10‐dioxa‐5‐azatricyclo[5.2.1.02,6]dec‐4‐en‐9‐one ((+)‐5) obtained in 6 steps from the Diels‐Alder adduct of furan to 1‐cyanovinyl (1S)‐camphanate ((+)‐3) was reduced to the corresponding endo‐alcohol (−)‐6 the treatment of which with HBr/AcOH provided (−)‐(3aS,4S,6R,7S,7aR)‐4β‐bromo‐3aβ,4,5,6,7,7aβ‐hexahydro‐2‐phenyl‐1,3‐benzoxazole‐6β,7α‐diyl diacetate ((−)‐17). Elimination of HBr with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) and acidic hydrolysis furnished (−)‐(1R,2S,3R,4R)‐4‐aminocyclohex‐5‐ene‐1,2,3‐triol (  (−)‐conduramine C1;(−)‐1).
Electrochemical Study of Phase‐Transfer Catalysis Reactions: The Williamson ether synthesis
Authors: Tan S. N. , Dryfe R. A. , Girault Hubert H.
Published: December 2004

The transfer properties of the ionic species involved in the Williamson ether synthesis by phase‐transfer catalysis were investigated using electrochemical techniques developed for the study of polarised liquid/liquid interfaces. This approach allows the measurement of the apparent partition coefficients of the transferring species. From these data, it is proposed that the role of the phase‐transfer catalyst salt in the reaction mechanism is to establish a Galvani distribution potential difference between the two phases which in turn acts as the driving force for transferring the reactive aqueous ions to the organic phase.
Bovine α‐Lactalbumin: Identification of two metal‐ion‐binding sites using the europium (III) luminescent probe
Authors: Bünzli Jean‐Claude G. , Pfefferlé Jean‐Marc
Published: December 2004

The luminescent EuIII ion has been used to probe the metal‐binding sites of bovine α‐lactalbumin (BLA) in D2O. Upon addition of apo‐BLA to an EuIII‐containing solution, the intrinsic luminescence of the protein is quenched, and the EuIII luminescence is enhanced. Luminescent titrations point to there being at least two different metal‐binding sites in the apo‐protein. Curve analysis of the high resolution 5D0←7F0 excitation spectra reveals the existence of three different environments for the bonded EuIII ions. Two environments, labelled Ia and Ib, give 5D0←7F0 bands very close in energy; they contain four negatively charged groups and are assigned to one site we identify as the calcium‐binding site. Site I is protected from solvent influences and is somewhat rigid, since it displays selectivity towards lanthanide ions. The origin of the two similar environments Ia and Ib could not be determined unambiguously. The third environment is ascribed to a nonspecific metal‐binding site in which the EuIII ion is more exposed to the solvent (site II). It is sequentially populated after saturation of site I, and its population is pH‐dependent. The affinity constant of EuIII for this site was estimated from the excitation spectra: log K2app  3.5(1). Assignment of the metal binding sites has been facilitated by comparison with model compounds, [Eu(dota)]− (dota  1,4,7,10‐tetraazacyclododecane N,N′,N″, N‴‐tetraacetate), [Eu(dtpa)]2− (dtpa  diethylenetriamine tetraacetate), and [Eu(bsa)] (bsa  bovine serum albumin). The usefulness and limits of the use of curve‐analysis procedures to unravel the various components of 5D0←7F0 excitation spectra in biological materials are also discussed.
N7‐DNA: Synthesis and Base Pairing of Oligonucleotides containing 7‐(2‐Deoxy‐β ‐D‐erythro‐pentofuranosyl)adenine (N7Ad)
Authors: Seela Frank , Winter Holger
Published: December 2004

The synthesis of oligonucleotides containing 7‐(2‐deoxy‐β ‐D‐erythro‐pentofuranosyl)adenine (N7Ad; 1) is described. Compound 1 was obtained from the precursor 4‐amino‐1H ‐imidazole‐5‐carbonitrile 2‐deoxyribonucleoside 6 and was found to be much more labile than Ad. The N6‐benzoyl protecting group (see 8) destabilized the N‐glycosylic bond further and was difficult to remove by NH3‐catalyzed hydrolysis. Therefore, a (dimethyl‐amino)methylidene residue was introduced (→9). Amidine 9 was blocked at OHC(5′) with the dimethoxytrityl residue ((MeO)2Tr), and phosphonate 4 as well as phosphoramidite 5 were prepared under standard conditions. Phosphonate 4 was employed in solid‐phase oligonucleotide synthesis. Homooligonucleotides as well as self‐complementary oligonucleotides were prepared. The oligomer d[(N7A)11‐A] (11) formed a duplex with d(T12) (13). Antiparallel chain polarity and reverse Watson‐Crick base pairing was deduced from duplex formation of the self‐complementary d[(N7A)8‐T8] (14).
[M(bpy)3] (M = Fe, Ru, Os): New Crystalline Materials from the reductive electrocrystallization of [M(bpy)3](PF6)2
Authors: Pérez‐Cordero Eduardo , Buigas Rosanna , Brady Nancy , Echegoyen Luis , Arana Claudia , Lehn Jean‐Marie
Published: December 2004

Reductive electrocrystallization at a constant current density (11.0–11.5 μA/cm2) of millimolar solutions of [M(bpy)3](PF6)2, where M = Fe, Ru, or Os, and bpy = 2,2′‐bipyridine in acetonitrile containing 0.1M Bu4NPF6 results in the formation of dark crystals on the Pt cathode. The crystals grow as long, thin, and shiny needles having a hexagonal cross section of 0.1–0.5 mm in diameter. Combustion microanalyses results are consistent with the composition for [Fe(bpy)3], [Ru(bpy)3], and [Os(bpy)3]. In addition, the chromophores are conserved, as confirmed by recording both the electronic and the 1H‐NMR spectra after reoxidation of the electrocrystals in humid air. The spectra are identical to those for authentic samples of [Fe(bpy)3]2+, [Ru(bpy)3]2+, and [Os(bpy)3]2+. A ratio of 2.0 ± 0.1 e−/molecule is observed upon completion of the controlled potential electrolysis of a solution of [M(bpy)3]2+, which results in the precipitation of a dark solid and the almost complete fading of the color of the original solution. Unexpectedly, the crystals do not exhibit an ESR signal. These data indicate the formation of novel materials, crystalline [Fe(bpy)3], [Ru(bpy)3], and [Os(bpy)3].
Asymmetric Total Synthesis of (11R, 12S, 13S, 9Z, 15Z)‐9, 12, 13‐Trihydroxyoctadeca‐9, 15‐dienoic Acid, a self‐defensive agent against rice‐blast disease
Authors: Baudat Alain , Vogel Pierre
Published: December 2004

The Diels‐Alder adduct of furan and 1‐cyanovinyl (1′R)‐camphanate was converted into methyl [(tert‐butyl)‐dimethylsilyl 5‐deoxy‐2, 3‐O‐isopropylidene‐β‐L‐ribo‐hexofuranosid] uronate ((+)‐4). Reduction with diisobutyl‐aluminium hydride gave the corresponding aldehyde which was condensed with the ylide derived from triphenyl‐(propyl)phosphonium bromide to give (1R, 2S, 3S, 4S)‐1‐[(tert‐butyl)dimethylsilyloxy]tetrahedro‐2, 3‐(isopropyl‐idenedioxy)‐4‐[(Z)‐pent‐2′ ‐enyl]furan ((+)‐7). Removal of the silyl protective group gave a mixture of the corresponding furanose that underwent Wittig reaction with the ylide derived from [8‐(methoxycarbonyl)‐octyl]triphenylphosphonium bromide to yield methyl (11R, 12S, 13S, 9Z, 15Z)‐13‐hydroxy‐11, 12‐(isopropylidene‐dioxy)octadeca‐9, 15‐dienoate ((−)‐9). Acidic hydrolysis, then saponification afforded (11R, 12S, 13S, 9Z, 15Z)‐11, 12, 13‐trihydroxyoctadeca‐9, 15‐dienoic acid (1).
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
Authors: Pitsch Stefan , Pombo‐Villar Esteban , Eschenmoser Albert
Published: December 2004

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.
Asymmetric Alkylations of a Sultam‐Derived Glycine Equivalent: Practical preparation of enantiomerically pure α‐amino acids
Authors: Oppolzer Wolfgang , Moretti Robert , Zhou Changyou
Published: December 2004

Alkylation of the chiral glycine derivative 2 with “activated” organohalides under ultrasound‐assisted phasetransfer catalysis or with activated and nonactivated organohalides in anhydrous medium provides (mostly crystalline) alkylation products 3. Acidic hydrolysis of the pure products 3 gives (aminoacyl)sultams 4 which by mild saponification furnish pure α‐amino acids 5 in good overall yields from 2, along with recovered auxiliary 1 (Scheme 1). Pure ω‐protected α,ω‐diamino acids and α‐amino‐ω‐(hydroxyamino)acids 12–16 are readily accessible from (ω‐haloacyl)sultams 3 via reaction with N‐nucleophiles followed by acidic and basic hydrolyses (Scheme 2). A reliable determination of the enantiomeric purity of α‐amino acids using HPLC analysis of their N‐(3,5‐dinitrobenzoyl)prolyl derivatives 17 is presented.
The Enantioselective Synthesis of the ‘Southern Part’ of Soraphen A
Authors: Loubinoux Bernard , Sinnes Jean‐Luc , O'Sullivan Anthony C. , Winkler Tammo
Published: December 2004

Using a series of enantioselective aldol condensations followed by an ester enolate addition, the cyclic hemiacetal 2 was prepared stereospecifically. Hemiacetal 2 represents the synthetically most challenging ‘southern part’ of the antifungal macrolide soraphen A (1). Spontaneous enolisation of 26, the C(2) epimer of 2, revealed that 2 is the most stable diastereoisomer at room temperature.
Oligosaccharide Analogues of Polysaccharides. Part 2. Regioselective deprotection of monosaccharide‐derived monomers and dimers
Authors: Alzeer Jawad , Vasella Andrea
Published: December 2004

The Me3SiC(1) bond of the bis‐(trimethylsilyl)ethynylated anhydroalditol 2 is selectively cleaved with BuLi to yield 3/4, while AgNO2/KCN in MeOH cleaves the Me3SiC(2′) bond, leading to 5 (Scheme 1). Both Me3Si groups are removed with NaOH in MeOH (→ 7), the (i‐Pr)3Si group is selectively cleaved with HCl in aq. MeOH ( →6); all silyl substituents are removed with Bu4NF ( →8). Acetolysis transformed 9 into 13, which was desilylated to 14, while thiolysis of 9 led to a mixture 11/12. The tetraacetate 14 has also been obtained from 9 via 10. Oxidative dimerisation of either 3 or 5, or of a mixture 3/5 yields only the homodimers 15 and 16 (Scheme 2); treatment of 16 with AgNO2/KCN yielded 17, deprotection proceeding much more slowly than the cleavage of the Me3SiC(2′) group of 2. The iodoalkyne 20, required for the cross‐coupling with 5 according to Cadiot‐Chodkiewicz, was prepared by deprotection of 3/4 to 18, methoxymethylation (→19), and iodination. Cross‐coupling yielded mostly 21, besides the homodimer 22. Similarly, cross‐coupling of 20 and 23 (obtained from 5) led to 24 and 22. The structure of 24 was established by X‐ray analysis (Fig.), showing a C(6)–C(5′) distance of 5.2 Å. The conditions for deprotecting 2 were applied to 21, and led to 25 (AgNO2/KCN), 26 (aq. NaOH), 27 (Bu4NF), and 29 (HCl/MeOH; Scheme 3). Attempted deprotection of the propargylic‐ether moiety with BuLi, however, failed. The dimer 27 was further deprotected to 28. Acetolytic (Ac2O/Me3SiOTf) debenzylation of the dimer 30, obtained from 10, gave 31 (83%) which was deacetylated to 32 (Scheme 4). Cross‐coupling of 5 and the bromoalkyne 33, obtained from 10, yielded 34; again, acetolysis proceeded well, leading to 35. The cellobiose derivative 38 was prepared from the lactone 36 via 37. The glycosidic linkage of 38 proved resistant to the conditions of acetolysis, leading to 39. Acetolysis of the benzylated thiophene 40 (from 30 with Na2S) yielded the octaacetate 41, but proceeded in substantially lower yields (50%).
Oligosaccharide Analogues of Polysaccharides. Part 1. Concept and synthesis of monosaccharide‐derived monomers
Authors: Alzeer Jawad , Cai Chengzhi , Vasella Andrea
Published: December 2004

It is proposed to study the influence of interresidue H‐bonds on the structure and properties of polysaccharides by comparing them to a series of systematically modified oligosaccharide analogues where some or all of the glycosidic O‐atoms are replaced by buta‐1,3‐diyne‐1,4‐diyl groups. This group is long enough to interrupt the interresidue H‐bonds, is chemically versatile, and allows a binomial synthesis. Several approaches to the simplest monomeric unit required to make analogues of cellulose are described. In the first approach, allyl α‐D‐galactopyranoside (1) was transformed via 2 and the tribenzyl ether 3 into the triflate 4 (Scheme 2). Substitution by cyanide (→ 5–7) followed by reduction with DIBAH led in high yield to the aldehyde 9, which was transformed into the dibromoalkene 10 and the alkyne 11 following the Corey‐Fuchs procedure (Scheme 3). The alkyne was deprotected via 12 or directly to the hemiacetal 13. Oxidation to the lactone 14, followed by addition of lithium (trimethylsilyl)acetylide Me3SiCCLi/CeCl3 (→ 15) and reductive dehydroxylation afforded the disilylated dialkyne 16. The large excess of Pd catalyst required for the transformation 11 → 13 was avoided by deallylating the dibromoalkene 10 (→ 17 → 18), followed by oxidation to the lactone 19, addition of Me3SiCCLi to the anomeric hemiketals 20 (α‐D/β‐D 7:2), dehydroxylation to 21, and elimination to the monosilylated dialkyne 22 (Scheme 3). In an alternative approach, treatment of the epoxide 24 (from 23) with Me3SiCCLi/Et2AlCl according to a known procedure gave not only the alkyne 27 but also 25, resulting from participation of the MeOCH2O group (Scheme 4). Using Me3Al instead of Et2AlCl increased the yield and selectivity. Deprotection of 27 (→ 28), dibenzylation (→ 29), and acetolysis led to the diacetate 30 which was partially deacetylated (→ 31) and oxidized to the lactone 32. Addition of Me3SiCCLi/TiCl4 afforded the anomeric hemiketals 33 (α‐D/β‐D 3:2) which were deoxygenated to the dialkyne 34. This synthesis of target monomers was shortened by treating the hydroxy acetal 36 (from 27) with (Me3SiCC)3Al (Scheme 5): formation of the alkyne 37 (70%) by fully retentive alkynylating acetal cleavage is rationalised by postulating a participation of HOC(3). The sequence was further improved by substituting the MeOCH2O by the (i‐Pr)3SiO group (Scheme 6); the epoxide 38 (from 23); yielded 85% of the alkyne 39 which was transformed, on the one hand, via 40 into the dibenzyl ether 29, and, on the other hand, after C‐desilylation (→ 41) into the dialkyne 42. Finally, combined alkynylating opening of the oxirane and the 1,3‐dioxolane rings of 38 with excess Et2Al CCSiMe3 led directly to the monomer 43 which is thus available in two steps and 77% yield from 23 (Scheme 6).
Oligosaccharide Analogues of Polysaccharides. Part 3. A new protecting group for alkynes: Orthogonally protected dialkynes
Authors: Cai Chengzhi , Vasella Andrea
Published: December 2004

Dialkynes of the type 3 (Scheme 1) are regioselectively deprotected by treating them either with base in a protic solvent (→4), or– after exposing the OH group– by catalytic amounts of base in an aprotic solvent (→5 and 8). The Me3Si‐protected 12 (Scheme 2) is inert to catalytic BuLi/THF which transformed 11 into 9, while K2CO3/MeOH transformed both 10 into 9, and 12 into 13, evidencing the requirement for a more hindered (hydroxypropyl)silyl substituent. C‐Silylation of the carbanions derived from 17–19 (Scheme 3) with 15 led to 20–22, but only 22 was obtained in reasonable yields. The key intermediate 27 was, therefore, prepared by a retro‐Brook rearrangement of 23, made by silylating the hydroxysulfide 16 with 15. The OH group of 27 was protected to yield the {[dimethyl(oxy)propyl]dimethylsilyl}acetylenes (DOPSA's) 21, 28, and 29. The orthogonally protected acetylenes 20–22, 28, and 29 were de‐trimethylsilylated to the new monoprotected acetylene synthons 30–34. The scope of the orthogonal protection was checked by regioselective deprotection of the dialkynes 39–42 (Scheme 4), prepared by alkylation of 35 (→39), or by Pd0/CuI‐catalyzed cross‐coupling with 36–38 (→40–42). The cross‐coupling depended upon the solvent and proceeded best in N,N,N′,N′ ‐teramethylethylenediamine (TMEDA). Main by‐product was the dimer 43. On the one hand, K2CO3/MeOH removed the Me3Si group and transformed 39–42 into the monoprotected 44–47; catalytic BuLi/THF, on the other hand, transformed the alcohols 48–51, obtained by hydrolysis of 39–42, into the monoprotected dialkynes 52–55, all steps proceeding in high yields. Addition of the protected DOPSA groups to the lactones 56 (→57–59) and 62 (→63) (Schemes 5 and 6) gave the corresponding hemiketals. Reductive dehydroxylation of 57 and 58 failed; but similar treatment of 59 yielded the alcohol 61. Similarly, 63 was transformed into 64 which was protected as the tetrahydropyranyl (Thp) ether 65. In an optimized procedure, 62 was treated sequentially with lithiated 31, BuLi, and Me3SiCl (→66), followed by desilyloxylation to yield 60% of 67, which was protected as the Thp ether 68. Under basic, protic conditions, 68 yielded the monoprotected bisacetylene 69; under basic, aprotic conditions, 67 led to the monoprotected bisacetylene 70. These procedures are compatible with the butadiynediyl function. The butadiyne 73 was prepared by cross‐coupling the alkyne 69 and the iodoalkyne 71 (obtained from 70, together with the triiodide 72) and either transformed to the monosilylated 76 or, via 77, to the monosilylated 78. Formation of the homodimers 74 and 75 was greatly reduced by optimizing the conditions of cross–coupling of alkynes.