The 1,3-dipolar cycloaddition of the C-t-butyloxycarbonyl-N-mannosyl-nitrone 5, formed in situ fr... more The 1,3-dipolar cycloaddition of the C-t-butyloxycarbonyl-N-mannosyl-nitrone 5, formed in situ from the partially protected D-mannose-oxime 3 and the glyoxylate 4, to ethylene gave preferentially the (3S)-N-glycosyl-isoxazolidine 6 which was transformed into the 3-isoxazolidine-carboxylate (L-5-oxaproline ester) 12 and into some derivatives thereof. The (S)-configuration of 12 was proved by chemical correlation with a derivative of L-asparagine. The D-5-oxaproline ester was obtained from the corresponding N-ribosyl-nitrone 24. Two protected dipeptides containing either C-terminal- (28) or N-terminal-5-oxaproline (= Opro) (30) were synthesized. Starting from 12, the analogue 1 of captopril® (2) was prepared and its activity as an inhibitor of the angiotensin-converting-enzyme (ACE) was examined.
The anthraquinone derivatives T‐x‐x (x = 2, 4, and 8), possessing two cellobiosyl, cellotetraosyl... more 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 Iβ. 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.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
The pairing propensity of new DNA analogues with a phosphinato group between O−C(3′) and a newly ... more The pairing propensity of new DNA analogues with a phosphinato group between O−C(3′) and a newly introduced OCH2 group at C(8) and C(6) of 2′-deoxyadenosine and 2′-deoxyuridine, respectively, was evaluated by force-field calculations and Maruzen model studies. These studies suggest that these analogues may form autonomous pairing systems, and that the incorporation of single modified units into DNA 14mers is compatible with duplex formation. To evaluate the incorporation, we prepared the required phosphoramidites 3 and 4 from 2′-deoxyadenosine and 2′-deoxyuridine, respectively. The phosphoramidite 5 was similarly prepared to estimate the influence of a CH2OH group at C(8) on the duplex stability. The modified 14-mers 6 – 9 were prepared by solid-phase synthesis. Pairing studies show a decrease of the melting temperature by 2.5° for the duplex 13⋅9, and of 6 – 8° for the duplexes 10⋅6, 11⋅6, 13⋅7, and 14⋅8, as compared to the unmodified duplexes.
Abstract The one-step synthesis of various O -benzyl-protected glyconotetrazoles from the corresp... more Abstract The one-step synthesis of various O -benzyl-protected glyconotetrazoles from the corresponding glyconolactams is reported. The method is superior to the previously employed cycloaddition of azidonitriles as it uses readily available starting materials and leads to higher yields.
A new synthesis of pteridines possessing a (substituted) (Z)‐3‐hydroxyprop‐1‐enyl group at C(6) i... more A new synthesis of pteridines possessing a (substituted) (Z)‐3‐hydroxyprop‐1‐enyl group at C(6) is based on the acylation of 4‐amino‐5‐nitrosopyrimidines with dienoic acid chlorides, followed by a high‐yielding intramolecular hetero‐Diels–Alder cycloaddition and cleavage of the NO bond leading to 4. Thermolysis of the resulting pteridines 4 possessing a benzyloxy group at C(4) led to the products 5, resulting from isomerisation of the 3‐hydroxyprop‐1‐enyl to an 3‐oxopropyl side chain, while the analogous pteridine 8 possessing an NH2 group at C(4) remained unaffected.
The structure of the α‐chloronitroso ether 1, obtained from the hydroximolactone 2 and tert‐butyl... more The structure of the α‐chloronitroso ether 1, obtained from the hydroximolactone 2 and tert‐butyl hypochlorite (89%), was established by X‐ray crystallographic analysis. The [4 + 2] cycloadditions of 1 with the dienes 3 and 8–11 led to the N‐unsubstituted 3,6‐dihydro‐2H‐1,2‐oxazines 6 and 12–16 in high enantiomeric excess (Table 1). Due to the additional α‐alkoxy group, the reactivity of 2 is much superior to the one of known α‐chloronitrosoalkanes. The reactive conformation of 1 was deduced from the X‐ray analysis as well as the high diastereoselectivity of the cycloadditions. The importance of the α‐alkoxy group was evidenced from the similar reactivity of the racemic α‐chloronitroso ethers 25–27 which were prepared from the hydroximo ethers 28–30 and tert‐butyl hypochlorite.
The 1,3-dipolar cycloaddition of the C-t-butyloxycarbonyl-N-mannosyl-nitrone 5, formed in situ fr... more The 1,3-dipolar cycloaddition of the C-t-butyloxycarbonyl-N-mannosyl-nitrone 5, formed in situ from the partially protected D-mannose-oxime 3 and the glyoxylate 4, to ethylene gave preferentially the (3S)-N-glycosyl-isoxazolidine 6 which was transformed into the 3-isoxazolidine-carboxylate (L-5-oxaproline ester) 12 and into some derivatives thereof. The (S)-configuration of 12 was proved by chemical correlation with a derivative of L-asparagine. The D-5-oxaproline ester was obtained from the corresponding N-ribosyl-nitrone 24. Two protected dipeptides containing either C-terminal- (28) or N-terminal-5-oxaproline (= Opro) (30) were synthesized. Starting from 12, the analogue 1 of captopril® (2) was prepared and its activity as an inhibitor of the angiotensin-converting-enzyme (ACE) was examined.
The anthraquinone derivatives T‐x‐x (x = 2, 4, and 8), possessing two cellobiosyl, cellotetraosyl... more 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 Iβ. 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.
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
The pairing propensity of new DNA analogues with a phosphinato group between O−C(3′) and a newly ... more The pairing propensity of new DNA analogues with a phosphinato group between O−C(3′) and a newly introduced OCH2 group at C(8) and C(6) of 2′-deoxyadenosine and 2′-deoxyuridine, respectively, was evaluated by force-field calculations and Maruzen model studies. These studies suggest that these analogues may form autonomous pairing systems, and that the incorporation of single modified units into DNA 14mers is compatible with duplex formation. To evaluate the incorporation, we prepared the required phosphoramidites 3 and 4 from 2′-deoxyadenosine and 2′-deoxyuridine, respectively. The phosphoramidite 5 was similarly prepared to estimate the influence of a CH2OH group at C(8) on the duplex stability. The modified 14-mers 6 – 9 were prepared by solid-phase synthesis. Pairing studies show a decrease of the melting temperature by 2.5° for the duplex 13⋅9, and of 6 – 8° for the duplexes 10⋅6, 11⋅6, 13⋅7, and 14⋅8, as compared to the unmodified duplexes.
Abstract The one-step synthesis of various O -benzyl-protected glyconotetrazoles from the corresp... more Abstract The one-step synthesis of various O -benzyl-protected glyconotetrazoles from the corresponding glyconolactams is reported. The method is superior to the previously employed cycloaddition of azidonitriles as it uses readily available starting materials and leads to higher yields.
A new synthesis of pteridines possessing a (substituted) (Z)‐3‐hydroxyprop‐1‐enyl group at C(6) i... more A new synthesis of pteridines possessing a (substituted) (Z)‐3‐hydroxyprop‐1‐enyl group at C(6) is based on the acylation of 4‐amino‐5‐nitrosopyrimidines with dienoic acid chlorides, followed by a high‐yielding intramolecular hetero‐Diels–Alder cycloaddition and cleavage of the NO bond leading to 4. Thermolysis of the resulting pteridines 4 possessing a benzyloxy group at C(4) led to the products 5, resulting from isomerisation of the 3‐hydroxyprop‐1‐enyl to an 3‐oxopropyl side chain, while the analogous pteridine 8 possessing an NH2 group at C(4) remained unaffected.
The structure of the α‐chloronitroso ether 1, obtained from the hydroximolactone 2 and tert‐butyl... more The structure of the α‐chloronitroso ether 1, obtained from the hydroximolactone 2 and tert‐butyl hypochlorite (89%), was established by X‐ray crystallographic analysis. The [4 + 2] cycloadditions of 1 with the dienes 3 and 8–11 led to the N‐unsubstituted 3,6‐dihydro‐2H‐1,2‐oxazines 6 and 12–16 in high enantiomeric excess (Table 1). Due to the additional α‐alkoxy group, the reactivity of 2 is much superior to the one of known α‐chloronitrosoalkanes. The reactive conformation of 1 was deduced from the X‐ray analysis as well as the high diastereoselectivity of the cycloadditions. The importance of the α‐alkoxy group was evidenced from the similar reactivity of the racemic α‐chloronitroso ethers 25–27 which were prepared from the hydroximo ethers 28–30 and tert‐butyl hypochlorite.
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