Oligosaccharide Analogues of Polysaccharides. Part 12. Synthesis of ‘acetyleno-saccharide’-derived cyclodextrin analogues

‘Acetyleno-oligosaccharides’ in which two terminal ethynyl substituents enclose an angle (significantly) below 180° are building blocks for the preparation of cyclodextrin analogues. This is illustrated by the preparation of a cyclotrimer and a cyclotetramer; the C₃-symmetrical cyclotrimer 18 (Scheme 1) was synthesized in 13 steps (7.7%) and the C₄-symmetrical cyclotetramer 51 (Scheme 3) in 14 steps (4.3%) from the known dialkyne 21. The solubilities of 18 and 51 in H₂O were determined by gravimetry; a saturated solution is 130 mM in the trimer 18 and 12.8 mM in the tetramer 51 . The dependence of the optical rotation of 18 and 51 in H₂O on the concentration, and the concentration dependence of the ¹H-NMR chemical shift of the signals of the ¹CH groups of 51 (D₂O) suggest that there is no significant self-association of 18 and 51 .     

Oligosaccharide Analogues of Polysaccharides. Part 26

The anthraquinone derivatives T‐x‐x ( x = 2, 4, and 8), possessing two cellobiosyl, cellotetraosyl, and cellooctaosyl chains, respectively, C‐glycosidically bonded at C(1) and C(8) were synthesised as potential mimics of cellulose I. The anthraquinone template enforces a parallel orientation of the cellodextrin chains at a distance corresponding to the one between the crystallographically independent chains of cellulose I, and the ethynyl and buta‐1,3‐diynyl linker units ensure an appropriate phase shift between them. The H‐bonding of the T‐x‐x mimics was analysed and compared to the one of the mono‐chained analogues T‐x and of the known cellulose II mimics N‐x‐x and N‐x where one or two cellodextrin chains are O‐glycosidically bonded to naphthalene‐1,8‐diethanol, or to naphthalene‐1‐ethanol. The OH signals of T‐x and T‐x‐x in solution in (D₆)DMSO were assigned on the basis of DQFCOSY, HSQC, and TOCSY (only of T‐4, T‐4‐4 , and T‐8‐8 ) spectra and on a comparison with the spectra of N‐x and N‐x‐x. Hydrogen bonding was analysed on the basis of the chemical shift of OH groups and its temperature dependence, coupling constants, SIMPLE ¹H‐NMR experiments, and ROESY spectra. T‐4‐4 and T‐8‐8 in (D₆)DMSO appear to adopt a V‐shape arrangement of the cellosyl chains, avoiding inter‐chain H‐bond interactions. The well‐resolved solid‐state CP/MAS ¹³C‐NMR spectra of the mono‐chained T‐x ( x = 1, 2, 4, and 8) show that only T‐8 is a close mimic of cellulose II. While the solid‐state CP/MAS ¹³C‐NMR spectrum of the C₁‐symmetric diglucoside T‐1‐1 is well‐resolved, the spectra of T‐2‐2 and T‐4‐4 show broad signals, and that of T‐8‐8 is rather well resolved. The spectrum of T‐8‐8 resembles that of cellulose I_β. A comparison of the X‐ray powder‐diffraction spectra of T‐8‐8 and T‐8 with those of celluloses confirms that T‐8‐8 is a H‐bond mimic of cellulose I and T‐8 one of cellulose II. Surprisingly, there is little difference between the CP/MAS ¹³C‐NMR spectra of the acetyl protected mono‐chained C‐glycosylated anthraquinone derivatives A‐x and the double‐chained A‐x‐x ( x = 2, 4, and 8). The spectra of A‐4 and A‐4‐4 resemble strongly the one of cellulose triacetate I ( CTA I ). The (less well‐resolved) spectra of the cellooctaosides A‐8 and A‐8‐8 , however, resemble the one of CTA II . The similarity between the solid‐state CP/MAS ¹³C‐NMR spectra of A‐4 and A‐4‐4 to the one of CTA I , and of A‐8 and A‐8‐8 to the one of CTA II is opposite to the observations in the acetylated cellodextrin series. The mono‐chained A‐x cellulose triacetate mimics 21 ( A‐2 ), 32 ( A‐4 ), and 55 ( A‐8 ) were synthesised by Sonogashira coupling of the cellooligosyl‐ethynes 15, 28 , and 50 , followed by selective deacetylation. Complete deacetylation provided the corresponding T‐x mimics. The double‐chained A‐x‐x mimics 24 ( A‐2‐2 ), 35 ( A‐4‐4 ), and 58 ( A‐8‐8 ) were prepared from A‐x by triflation and Sonogashira coupling with the cellosyl‐buta‐1,3‐diynes 19, 31 , and 53 . Their deacetylation provided the corresponding T‐x‐x mimics 25, 36 , and 59 . The cellooligosyl‐ethynes and cellooligosyl‐buta‐1,3‐diynes required for the Sonogashira coupling were prepared by stepwise glycosylation of the partially O‐benzylated β‐cellobiosyl‐ethyne and β‐cellobiosyl‐buta‐1,3‐diyne 13 and 17 , respectively, with the cellobiosyl donor 2 and the cellohexaosyl donor 47 .     

Oligosaccharide Analogues of Polysaccharides. Part 1. Concept and synthesis of monosaccharide-derived monomers

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

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.     

Oligosaccharide Analogues of Polysaccharides. Part 4. Synthesis of a monosaccharide-derived octamer

NaSMe in toluene leads to regioselective de-C-silylation of the bis[(trimethylsilyl)ethynyl]saccharide 2 , but to decomposition of butadiynes such as 1 or 12 . We have, therefore, combined the known reagent-controlled, regioselective desilylation of 2 and of 12 (AgNO₂/KCN) with a substrate-controlled regioselective de-C-silylation, based on C-silyl groups of different size. This combination was studied with the fully protected 3 which was mono-desilylated to 4 or to 5 (Scheme 1). Triethylsilylation of 5 (→ 6 ) was followed by removal of the Me₃Si group (→ 7 ), introduction of a (t-Bu)Me₂Si group (→ 8 ) and removal of the Et₃Si group yielded 9 ; these high-yielding transformations proceed with a high degree of selectivity. Iodination of 4 gave 10 . The latter was coupled with 5 to the homodimer 11 and the heterodimer 12 , which was desilylated to 13 . The second building block for the tetramer was obtained by coupling 14 (from 7 ) with 5 , leading to 15 and 16 . Removal of the Me₃Si group (→ 17 ) and iodination led to 18 which was coupled with 13 to the homotetramer 20 and the heterotetramer 19 (Scheme 2). Deprotection of 19 gave 21 , which was, on the one hand, iodinated to 22 , and, on the other hand, protected by the (t-Bu)Me₂Si group (→ 23 ). Removal of the Et₃Si group (→ 24 ) and coupling afforded the homooctamer 26 and the heterooctamer 25 . Yields of iodination, silylation, and desilylation were consistently high, while heterocoupling proceeded in only 50–55%. Cleavage of the (i-Pr)₃SiC and MeOCH₂O groups of 11 (→ 27 ), 15 (→ 28 ), 20 (→ 29 ) and 26 (→ 30 ) proceeded in high yields (Scheme 3). Complete deprotection in two steps of the heterocoupling products 16 (→ 31 → 32 ), 19 (→ 33 → 34 ), and 25 (→ 35 → 36 ) gave the unprotected dimer 32 , tetramer 34 , and octamer 36 in high yields (Scheme 4). Only the dimer 32 is soluble in H₂O; the ¹H-NMR spectra of 32 , 34 , and 36 in (D₆)DMSO (relatively low concentration) show no signs of association.     

Oligonucleotide Analogues with a ‘Nucleobase‐Including Backbone’. Part 10

The dinucleoside analogues 24, 25, 28 – 30 , and 33 associate in CDCl₃ solution. Association constants, as determined from the concentration‐dependent chemical shift for H? N(3) of the uridine moiety and from thermodynamic parameters, range from 265 M ^?1 ( 33 ) to 3220 M ^?1 ( 30 ). The association of 31 in CDCl₃ is too strong to be determined (concentration independent δ(H? N(3)) of ca. 12.8 ppm) and the fully deprotected dimer 32 proved insufficiently soluble in CDCl₃. This observation strongly evidences that structural differentiation of oligonucleotides and their analogues into backbone and nucleobases is not required for pairing. The dinucleotide analogues were prepared by O‐alkylation of C(8)‐unsubstituted or of C(8)‐oxymethylated, partially protected adenosines by the C(6)‐mesyloxy‐ or C(6)‐halomethylated uridines 20 – 22 , followed by partial or total deprotection.     

Oligosaccharide Analogues of Polysaccharides. Part 9. Synthesis and Thermolysis of Acetylenosaccharide-Derived 1,2-Dialkynylbenzenes

Thermolysis of the 1,2-bis(glucosylalkynyl)benzenes 6 and 16 was studied to evaluate the effects of intramolecular H-bonding on the activation energy of the Bergman-Masamune-Sondheimer cycloaromatization, and to evaluate the use of the cycloaromatization for the synthesis of di-glycosylated naphthalenes. The dialkynes were prepared by cross-coupling of the O-benzylated or O-silylated glucosylalkynes 1 and 4 (Scheme 1). Thiolysis of the known 1 , or acetolysis of 1 , followed by deacetylation ( →2→3 ) and silylation gave 4 . Cross-coupling of 1 or 4 with iodo- or 1,2-diiodobezene depended upon the nature of the added amine and on the protecting group, and led to the mono- and dialkynylbenzenes 5 and 6 , or 12, 13 , and 15 , respectively. The benzyl ethers 5 and 6 gave poor yields upon acetolysis catalyzed by BF₃ · OEt₂, while Ac₂O/CoCl₂ · 6 H₂O transformed 6 in good yields into the regioselectively debenzylated 10 . Desilylation of 7 and 13 gave the alcohols 8 and 14 , respectively. Thermolysis of 6 in PhCl gave 22 and 23 , independently of the presence or absence of 1,4-cyclohexadiene; 23 was formed from 22 (Scheme 2). Acetolysis of 22 gave the hexaacetate 24 that was completely debenzylated by thiolysis, yielding the diol 26 and trans-stilbene, evidencing the nature and position of the bridge between the glucosyl moieties (Scheme 3). Thiolysis of 22 yielded the unprotected 2,3-diglucosylnaphthalene 28 , a new type of C-glycosides. Depending upon conditions, hydrogenation of 22 led to 29 (after acetylation), 30 , or 32 . NMR and particularly NOE data evidence the threo-configuration of the bridge. The structure of 23 was confirmed by hydrolysis to the diol 34 and diphenylacetaldehyde, and by correlation of 23 with 22 via the common product 31 . Formation of 22 is rationalized by a Bergman cyclization to a diradical, followed by regioselective abstraction of a H-atom from the BnO? C(2) group, and diastereoselective combination of the doubly benzylic diradical (Scheme 4). While thermolysis of 3 in EtOH sets in around 140°, 16 did not react at 160° and decomposed at 180–220°. No evidence for intramolecular H-bonds of 16 , as compared to 14 , were found.     

Oligosaccharide Analogues of Polysaccharides. Part 2. Regioselective deprotection of monosaccharide-derived monomers and dimers

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 18 , Synthesis of Cyclic Hybrids of 2,2′-Bipyridine and Acetylenosaccharides

We report the efficient construction of cyclic hybrids of 2,2′-bipyridine and acetylenosaccharides from readily available building blocks involving a double Castro-Stephens coupling of an O-protected and an O-unprotected, mono-C-silylated 1,4-cis-diethynylated 1,5-anhydroglucitol (see 2 and 6 , resp.) to 6,6′-dibromo-2,2′-bipyridine ( 1 ) followed by oxidative cyclization of the resulting dialkynes (see Scheme). UV Spectra of the C-alkynylated linear and cyclized bipyridines 8 and 10 show that these ligands complex a range of metal ions (Figs. 4 and 5).     

Heterogeneous ‘Organoclick’ Derivatization of Polysaccharides

Summary: A simple method for the direct catalytic heterogeneous modification of polysaccharides is presented. The novel method is exemplified by the combination of organic acid‐catalyzed esterification and copper‐catalyzed Huisgen reaction (click chemistry) to attach a fluorescent probe to solid cellulose. The heterogeneous ‘organoclick’ derivatization of cellulose allows for a mild, highly modular surface modification of cellulose under environmentally benign reaction conditions.

Schematic of the combined organic acid‐catalyzed esterification and copper‐catalyzed Huisgen reaction (click chemistry) to modify a polysaccharide with a fluorescent probe.     

Oligosaccharide Analogues of Polysaccharides. Part 5. Studies on the cross-coupling of alkynes and haloalkynes

The cross-coupling of the homopropargylic ether 1 and the halopropargylic ethers 2a and 2b was optimized, and aspects of the coupling mechanism were studied. Coupling promoted by Pd° and Cu¹ in the presence of an amine yielded a mixture of the heterodimer 3 and the homodimers 4 and 5 (Scheme 1). Optimizations were first directed at suppressing homo-coupling. Homo-coupling is partially due to a H/I exchange ( 1 + 2a ? 6 + 7 ) promoted by CuI and an amine. The exchange, but not the formation of homodimers, was largely suppressed in DMSO. The influence of phosphine ligands was also evaluated. Weaker σ-donors (with the exception of PPh₃) lead to a faster coupling and to a higher ratio of hetero- to homodimers, with P(fur)₃ leading to the cleanest reaction. Homodimers are also formed (together with I₂ · (i-Pr)₂NH) by reductive dimerization of the iodoalkyne 2a in the presence of [Pd₂(dba)₃], CuI, and (i-Pr)₂NH. Bulky and acceptor-substituted amines reduced the extent of the dimerization of 2a , but the bulkiest amines did not promote coupling. Better results were obtained by using the bromoalkyne 2b . Neither dimerization of 2b , nor H/Br exchange between 1 and 2b were observed. Coupling of 1 and 2b was slower than the one of 1 and 2a , but gave higher yields of the heterodimer 3 . The yield of 3 and the ratio of hetero-to homodimers was greatly improved by addition of LiI; no phosphine ligand is then required. While the oxidative addition of the iodoalkyne 2a to [Pd(PPh₃)₄] ( 2a → 8a ) was rapid, the one of the bromoalkyne 2b was much slower and proceeded via the η²-complex 9 as evidenced by ¹H-NMR spectroscopy. The rearrangement of 9 to the bromopalladium σ-complex 8b follows first-order kinetics (k = 0.014 min^?1). CuBr greatly increased the rate of this rearrangement. LiI caused rapid substitution of Br by I in the Pd σ-complex ( 8b → 8a ), but not in 9 , nor in 2b . The σ-complex 8a did not react with the alkyne 1 in the presence of (i-Pr)₂NH, unless Cu^I was added. The alkynes 10 or 1 did not react with CuI and either TMEDA or (i-Pr)₂NH to yield detectable amounts of the Cu-acetylides 11 or 12 . These observations are rationalized by the mechanism shown in Scheme 3, postulating the intermediacy of the binuclear alkyne-Pd-Cu complexes C and J , and some or all of E–H , and highlighting the role of Cu^I in this coupling.     

Oligosaccharide Analogues of Polysaccharides. Part 7. Synthesis of a monosaccharide-derived monomer for amylose and cyclodextrin analogues

The synthesis of monomers of type C (Scheme 1) is described. In a first approach, chloro-acetyl-addition to the dioxolane 2 (Scheme 2), followed by treatment of the resulting chlorides 3 (α-D /β-D 1:3) with excess AgOTf and Bu₃SnC?CSiMe₃ gave the axial C-alkynyl-glycoside 4 (31%) and the C-arylglycoside 5 (29%). The structure of the dialkyne 6 , obtained by deacetylation of 4 , was established by X-ray analysis. The yield of the C-alkynyl-glycoside was slightly improved by protecting the C(4)-ethynyl group as the triethysilyl derivative, but not by substituting the benzyl by allyl or 2,6-difluorobenzyl groups. Silylation of the diol 1 with (chloro)diethyl[2-(trimethylsilyl)ethynyl]silane ( 19 ) resulted in 90% of the monosilyl ether 20 . HO? C(3) of 20 should favor coordination of a Lewis acid to O? C(6), and intramolecular, inverting acetal opening should lead to the product of axial alkynylation. Indeed, treatment of 20 with in situ generated BuAlCl₂, followed by treatment of the crude product with 0.1M HCl in MeOH, gave the dialkynylated triol 22 in yields of 85 to 90%. Under similar conditions, the disilyl ether 21 reacted more slowly to 22 (75%). The slower reaction correlates with the assumed intramolecular interaction of the precoordinated Lewis acid with O? C(6) in 20 .     

Oligosaccharide Analogues of Polysaccharides,Part 22 , Synthesis of Cyclodextrin Analogues Containing a Buta‐1,3‐diyne‐1,4‐diyl or a Butane‐1,4‐diyl Unit

The peracetylated hexaamylose (maltohexaose) 18 was obtained by an improved acetolysis of cyclomaltohexaose (α‐cyclodextrin, α‐CD, 16 ), and transformed into the benzyl‐ and 4‐chlorobenzyl‐protected thioglycosides 22 and 23 , respectively (Scheme 2). Sequential chain elongation of 22 and 23 by glycosidation of the C‐ethynylated glucosides 9 and 11 gave the α‐anomeric heptaglycosides 24 and 26 , respectively, and their anomers 25 and 27 (Scheme 3). These were transformed into the glycosyl acceptors 28 , 30 , and 31 . Glycosidation of 28 and 30 by 13 and 15 , respectively, led to the benzyl‐protected octasaccharides 32 (αα₅α) and 33 (βα₅α), and to the chlorobenzylated analogues 34 (αα₅α) and 35 (βα₅α), while glycosidation of 31 led to the 4‐chlorobenzyl‐protected analogues 36 (αα₅β) and 37 (βα₅β) (Scheme 4). Hay coupling of O‐Bn‐ and O‐Ac‐protected linear octaoses 32 (αα₅α) and 33 (βα₅α) led to the cyclooctaamylose (γ‐cyclodextrin) analogues 38 and 43 , respectively (Scheme 5). Similarly, the 4‐chlorobenzyl‐protected analogues 34 and 35 gave 39 and 44 , and the anomeric linear precursors 36 and 37 provided the cyclootaamylose analogues 48 and 50 , respectively (Scheme 6). The influence of the constitution and configuration of the linear precursors on the rate and yield of the cyclisation was relatively weak. Deprotection and hydrogenation of 38 and 43 yielded the γ‐CD analogues 42 (αα₅α) and 47 (βα₅α), where one glycosidic O‐atom is replaced by a butanediyl group, while FeCl₃‐promoted dechlorobenzylation of 39 and 44 did not affect the butadiyne moiety and afforded the acetyleno γ‐CD's 40 (αα₅α) and 45 (βα₅α), respectively. Similarly, deprotection of 48 and 50 afforded the acetyleno γ‐CD analogues 49 (αα₅β) and 51 (βα₅β), respectively, which contain one butanediyl moiety instead of a glycosidic O‐atom. MM3* Force‐field calculations evidence the strong influence of the configuration and constitution of the new γ‐CD analogues on the shape of the cavity.     

Oligosaccharide Analogues of Polysaccharides,Part 23 , Synthesis of a Dimeric Acetyleno Cyclodextrin from a Mannopyranose‐Derived Dialkyne

The 1,4‐cis‐diethynylated α‐D ‐mannopyranose analogue 11 has been prepared from 1,6 : 2,3‐dianhydro‐β‐D ‐allopyranose ( 6 ) by alkynylating epoxide and acetal opening (Scheme 2). Eglinton coupling of 11 gave the cyclodimer 18 (Scheme 3). Crystal‐structure analysis of the corresponding bis(methanesulfonate) 19 revealed substantially bent butadiyne moieties; one mannopyranosyl ring adopts the ⁴C₁ and the other one a slightly distorted ^OS₂ conformation (Fig. 1). Hydrogenation of 18 , followed by deprotection, gave the stable butane‐1,4‐diyl‐bridged cyclodimer 21 (Scheme 3). Crystal‐structure analysis shows the ⁴C₁ conformation of the mannopyranosyl units (Fig. 2). The two butane fragments are characterised by a combination of gauche and antiperiplanar arrangements.     

Comparison of collisional activation by the ‘boundary effect’ vs. ‘tickle’ excitation in an ion trap mass spectrometer

It has been shown previously that collisional activation in an ion trap mass spectrometer can be achieved by storing parent ions within a narrow zone extending close to the theoretical boundaries β_r = 0 or β_z = 0 of the stability diagram. This procedure can be used for obtaining collision-induced dissociation of selected parent ions without the need to apply a precisely tuned resonant ‘tickle’ potential between the end-cap electrodes. In this investigation a comparison was made between the two methods (‘tickle’ and ‘boundary’) of activation based on the efficiency of parent-to-daughter conversion and on the relative abundance of daughter ions for a model system (the m/z 91/92 ratio for n-butylbenzene). The data show that, under conditions of maximum efficiency, a comparable amount of internal energy is present in the ions after activation with the two methods. However, with the ‘tickle’ technique it is possible to increase the internal energy of the parent ions even further, although at the expense of the efficiency, whereas in the case of the “boundary” activation, the conditions for optimum efficiency almost coincide with those for maximum activation and a drastic loss of ions follows any attempt to overcome these limits. It is also found that at any given q_z value used for storing and activating parent ions the permitted mass difference between parent and fragment ions is greater with ‘boundary’ than with ‘tickle’ excitation.     

Deoxy-nitrosugars. 6th communication. Stereoelectronic control in the reductive denitration of tertiary nitro ethers. A synthesis of ‘C-glycosides’

The separate, radical denitration with Bu₃SnH of the pyranose derivatives 3, 4, 9 , and 10 gave in good yields exclusively the ‘C-glycosides’ 5 and 11 , respectively (Scheme 1). Similar reduction of the cyclohexyl derivatives 15, 16, 19 and 20 gave 4:1 mixtures of 17, 18, 21 and 22 , respectively, always with predominant formation of an axial C,H-bond. In the furanose series a divergent behaviour was observed for the D -mannose-derived nitro ethers 25 and 27 and the D -ribose-derived nitro ethers 30 and 31 , respectively, in that the former two gave isomerically homogeneous reduction products ( 26 and 28 , respectively; Scheme 3) and the latter a 1:1 mixture of the diastereoisomers 32 and 33 (Scheme 4). The stereochemical results were explained on the basis of the stereoelectronic effect of the ring O-atom, the preferred conformation of the intermediate, pyramidal alkoxyalkyl radicals and steric effects in the trioxabicyclo [3.3.0]octane ring system.     

‘Face-to-Face’-Benzo-anellierte homologe Hypostrophene. Synthesen,Röntgenstrukturanalysen und PE-Spektren

‘Face-to-Face’ Benzo-anellated Homologous Hypostrophenes. Syntheses, X-Ray-Structure Analyses and PE Spectra ‘Face-to-face’ Benzo-anellated homologous hypostrophenes (series M ), of interest as substrates for [6 + 6]-photocycloaddition reactions, have been synthesized. From X-ray structural analyses of 13b and 13c shortest C? C distances of 2.80(2.76)/2.71 Å and interorbital angles (ω) of 129° (128°)/130° between the benzene rings have been determined. The PE spectra are discussed in the context of transannular π,π interactions.     

Oligosaccharide Analogues of Polysaccharides. Part 8. Orthogonally Protected Cellobiose-Derived Dialkynes. A Convenient Method for the Regioselective Bromo- and Protodegermylation of Trimethylgermyl- and Trimethylsilyl-protected Dialkynes

The cellobiose-derived dialkynes 14 and 15 were prepared by glycosidation of the acceptor 9 with the thioglycosides 12 (82%) and 13 (85%), respectively. The acceptor 9 was prepared from the known alcohol 2 via the lactone 7 in five steps (48% overall), and the donors 12 and 13 were prepared from the alkynylated anhydroglucose derivative 10 (60% overall). Acetolytic debenzylation of 14 and 15 (→ 16 and 17 , resp.) followed by deacylation of 16 yielded 60% of the cellobiose-derived dialkyne 18 . Deacylation of 14 (→ 19 ), methoxymethylation (→ 20 ) and trimethylgermylation led to the orthogonally protected dialkyne 21 (69% overall). Protodesilylation of 21 with K₂CO₃/MeOH gave 22 (90%), while the Me₃Ge group was selectively removed with CuBr (19 mol-%) in THF/MeOH to give 20 (95%). Treatment of 21 with aqueous HCl solution led to 19 (80%). Bromodegermylation of 21 (NBS/AgOOCCF₃) led to a mixture of 23 (85%) and 24 (11%). Similar conditions using CuBr instead of AgOOCCF₃ gave exclusively the bromoalkyne 23 (93%). The temperature dependence of the δ values of the OH resonances of 18 in (D₆)DMSO evidence a strong intramolecular H-bond between C(5′)? O…?HO? C(5).