摘要:

AbstractNucleophilicBingelcyclopropanation ofD2‐C76with bis[(S)‐1‐phenylbutyl] 2‐bromomalonate in toluene in the presence of base yielded three constitutionally isomeric pairs of diastereoisomeric mono‐adducts together with one other constitutional isomer. All seven mono‐adducts were isolated in optically pure form by prep. HPLC on a (S,S)‐Whelk‐O1chiral stationary phase. They represent the first optically pure adducts of an inherently chiral fullerene. Characterization by UV/VIS, CD,13C‐ and1H‐NMR spectroscopy allowed identification of pairs of stereoisomers and symmetry assignments: the two pairs of diastereoisomers which were isolated as the major product possessC1symmetry, whereas the third pair of diastereoisomers, which is a minor product, isC2‐symmetrical. The circular dichroism spectra of the optically active C76‐adducts showed very pronouncedCottoneffects resulting from strong chiroptical contributions of the chiral fullerene chromophore with the maximum observed Δε values being twice as high than those previously measured for optically active adducts of achiral fullerenes with a chiral addition pattern. Whereas the regioselectivity of mono‐additions to C70correlates with the degree of local bond curvature and the regioselectivity of multipleBingelcyclopropanations of C60with electronic parameters such as coefficients of thelowestunoccupiedmolecularorbital (LUMO), no such simple predictive correlations exist for the nucleophilic addition to C76. Despite full spectral characterization, an unambiguous structural assignment of the isolated compounds was not possible, except for the twoC2‐symmetrical isomers. Based on considerations of local bond curvature and the previous experiences with the chemistry of C70, the structures of theC2‐symmetrical stereoisomers were assigned as (S,S,fC)‐3and (S,S,fA)‐3, resulting from addition

ISSN:0018-019X    

DOI:10.1002/hlca.19960790702

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractThe phosphono and the tetrazolyl analogues4and5of 4‐methylumbelliferyl β‐D‐glucuronide (=(4‐methyl‐2‐oxo‐2H‐1‐benzopyran‐7‐yl β‐D‐glucopyranosid)uronic acid;6) were synthesized and evaluated as substrates of β‐glucuronidases. Similarly, the phenylcarbamate7and its phosphono analogue8were prepared and evaluated as inhibitors. To examine the diastereoselectivity of the phosphorylation, we also synthesized the protectedL‐ido‐D‐gluco‐, andD‐galacto‐configurated phospha‐glycopyranuronates12, 13, 21, 22, 34and35. Two strategies were followed. In the first one, the glucuronic acid19was decarboxylated to11and further transformed,via20, into the trichloroacetimidate10(Scheme 2). Phosphorylation of10with (MeO)3P yielded the diastereoisomers12and13, the diastereoselectivity depending on the solvent. In MeCN,12and13were obtained in a ratio of 1:1, while in non‐participating solvents theL‐ido12was by far the major diastereoisomer. The acetate11was inert to (MeO)3P, but reacted with (PhO)3P to the anomeric mixture21/22, in keeping with a stabilizing 1,3‐interaction in the intermediate phosphonium salt. Similarly, the phospha‐galacturonates34and35were prepared from the galactoside23viathe enol ether26, the lactone27, and the acetates28/29that were also transformed into the trichloroacetimidate33(Scheme 3). In the second, higher‐yielding strategy, phosphorylation of the pentodialdehyde39to40/41was followed by hydrolysis and acetylation to the phospha‐glucuronates43/44(Scheme 4). Transesterification to45/46, selective deacetylation to48/49, and formation of the trichloroacetimidates50/51were followed by glycosidation and deprotection to4. The tetrazole5was prepared from the lactones54/55viatheN‐benzylamides57/58that were treated with TfN3to give theN‐benzyltetrazoles59/60(Scheme 4). These were transformed into the trichloroacetimidates63/64, glycosylated to65, and deprotected. TheO‐carbamoylhydroximo‐lactone7derived from the glucuronate67/68, and the phosphonate analogue8were prepared by established methods. The phosphonate4is slowly hydrolyzed by theE. coliβ‐glucuronidase, but neither4nor the tetrazole5are affected by the bovine liver β‐glucuronidase (Table 4). The phenylcarbamate7ofD‐glucarhydroximo‐1,5‐lactone, but not its phosphonate analogue8, is an inhibitor (KI= 8 m̈M) of theE. coliβ‐glucuronidase. The bovine liver β

ISSN:0018-019X    

DOI:10.1002/hlca.19960790703

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractDimethyl diazomalonate (4) and thiobenzophenone (2a) do not react in toluene even after warming to 50°. After addition of catalytic amounts of Rh2(OAc)4, a smooth reaction under N2evolution afforded a mixture of thiiranedicarboxylate5and (diphenylmethylidene)malonate6(Scheme 2). A reaction mechanismviaan intermediate ‘thiocarbonyl ylide’7, formed by the addition of the carbenoid species8to the S‐atom of2a, is plausible. Similar reactions were carried out with 9H‐xanthene‐9‐thione (2b), 9H‐thioxanthene‐9‐thione (2c,Scheme 4), and 1,3‐thiazole‐5(4H)‐thione18(Scheme 6). In the cases of2band2c, spirocyclic 1,3‐dithiolanetetracarboxylates14aand14b, respectively, were obtained as the third product. Reaction mechanisms for their formation are proposed inScheme 5: S‐transfer from intermediate thiirane12to the carbenoid species yielded thioxomalonate15which underwent a 1,3‐dipolar cycloaddition with ‘thiocarbonyl ylide’16. An alternative is the formation of ‘thiocarbonyl ylide’17viacarbene addition to15, followed by 1,3‐dipolar

ISSN:0018-019X    

DOI:10.1002/hlca.19960790704

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractThe degradation of cefaclor (1), an oral cephalosporin antibiotic, was studied at 37° in a neutral aqueous medium by HPLC and1H‐NMR. Under these conditions,1underwent intramolecular aminolysis by the 7‐side‐chain NH2group on the β‐lactam moiety to give a piperazine‐2,5‐dione. The most prominent peak in the HPLC profile of a degradation solution from1was isolated by prep. HPLC. Mechanistically, the formation of this degradation productcis‐11from1involves the contraction from a six‐membered cephem ring to a five‐membered ring, which presumably takes placeviaa common episulfonium ion intermediate9(seeScheme). Loss of the Cl‐atom from 3‐chloro‐3‐cephem is a general reaction subseque

ISSN:0018-019X    

DOI:10.1002/hlca.19960790705

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractThe synthesis, structural characterization, and NO donor properties of a series of terfuroxan (= terfurazan trioxide) derivatives1a–hand2a–jare reported (Schemes 1and2). Structural assignments were confirmed principally by mass and13C‐ and1H‐NMR spectroscopy. The extent and the initial rate of NO release in the presence of thiol cofactor was evaluated for each derivative. Vasodilator effects of all the terfuroxan derivatives were evaluated on endothelium‐denuded strips of rat aorta precontracted with noradrenaline. Concentration‐response curves were also evaluated in the presence of 10 m̈Moxyhemoglobin (HbO2), a well known NO scavenger. The whole series displays high vasodilating potency; the most active terfuroxans (1a, b, gand2i) are 5–10 times as potent as glyceryl trinitrate taken as reference (seeTable 3). The potency decrease observed in the presence of HbO2agrees with the involvement of NO in the vasorelaxing action. The 4,3′:4′,4″ connection (series1; furoxan numbering) gives rise to the most potent compounds. The conformational factors seem to play important roles in the activity. No clear relationship between physico‐chemical properties of the substituents and potencies

ISSN:0018-019X    

DOI:10.1002/hlca.19960790706

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractFormation constants of ternary complexes of CuIIwith (S)‐amino‐acid amides ((S)‐phenylalaninamide, (S)‐prolinamide, and (S)‐tryptophanamide) and (R)‐ or (S)‐histidine and (R)‐ or (S)‐tyrosine were determined potentiometrically in aqueous solution. Significant stereoselectivity was presented by all three amides towards histidine, the diastereoisomeric complexes with ‘heterochiral’ ligands being more stable than those with ‘homochiral’ ligands (seeTable 3). The stereoselectivity observed with (S)‐phenylalaninamide and (S)‐tryptophanamide may be explained on the basis of hydrophobic stacking interactions between 1H‐imidazole and the aromatic side chain, favoured by the terdentate behaviour of histidine (seeFig.2), whereas repulsive effects seem to be prevalent with (S)‐prolinamide. Only (S)‐prolinamide and (S)‐phenylalaninamide show appreciable stereoselectivity with tyrosine, which is bidentate, probably on account of repulsive interactions. The present results on the stability of ternary complexes in solution allow to draw some conclusions on the mechanism of chiral discrimination performed by CuIIcomplexes of (S)‐amino‐acid amides added to

ISSN:0018-019X    

DOI:10.1002/hlca.19960790707

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractWe explore here an approach to mimic the structures and biological functions of protein loops in small synthetic molecules, by grafting the loop of interest onto an organic template comprising a bicyclic diketopiperazine, prepared by the formal coupling of (2S,4S)‐4‐aminoproline (Pro(NH2)) and aspartic acid (Asp). The Fmoc‐protected template4is used to prepare cyclo(‐Ala1‐Asn2‐Pro3‐Asn4‐Ala5‐ Ala6‐Temp‐) (5) and cyclo(‐Ala1‐Arg2‐Gly3‐Asp4‐Temp‐) (6) (where Temp = template derived from4), containing the Asn‐Pro‐Asn‐Ala (NPNA) and Arg‐Gly‐Asp (RGD) motifs. The conformational properties of these molecules are studied in aqueous solution by NMR and simulated‐annealing methods. The NPNA motif, an immunodominant epitope on the circumsporozoite surface protein of the malaria parasitePlasmodium falciparum, is shown to adopt a stable type‐I β‐turn in5. The template in5adopts a preferred conformation with Pro(NH2)χ1≈︁ −35° and the Asp moiety χ1≈︁ 70°. A different template conformation is inferred for6, with Pro(NH2)χ1≈︁ 0°, but the ARGD loop appears by NMR to undergo rapid conformational averaging. Solid‐phase binding assays reveal that6displays mode

ISSN:0018-019X    

DOI:10.1002/hlca.19960790708

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractThe chiralN‐(2‐benzoylethyl)‐N‐tosylglycine esters5a–hand the α‐amino‐γ‐keto ester6were prepared from γ‐(tosylamino) alcohols7a–h. Irradiation of compounds5a–c, egavecis‐3‐hydroxyproline esters20–23(Scheme 6), partly with complete asymmetric induction by the C(1′)‐substituent, whereas6gave enantiomerically pure 4‐hydroxy‐4‐phenyl‐L‐proline esters24in good yield but low de (Scheme 6). The de of the photocyclization depended on the nature and/or size of the C(1′)‐substituents. Irradiation of ketones5dand5f, bearing H‐atoms at C(γ) with respect to the keto function, gave cyclobutanols (Scheme 9) in low yields besides the preferredNorrish‐type‐II cleavage product. Cyclopentanol25was a by‐product of the photocyclization of5cas a result of HC(δ) abstraction from thet‐Bu group. The structure of pro

ISSN:0018-019X    

DOI:10.1002/hlca.19960790709

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

Abstract6‐Aminopyrazin‐2(1H)‐one, when incorporated as a pyrimidine‐base analog into an oligonucleotide chain, presents a H‐bond acceptor‐donor‐donor pattern to a complementary purine analog. When paired with the corresponding donor‐acceptor‐acceptor purine in oligonucleotides, the heterocycle selectively contributes to the stability of the duplex, presumably by forming a base pair ofWatson‐Crickgeometry joined by a non‐standard H‐bonding pattern. Aspects of the nucleoside chemistry, including syntheses of the β‐furanosyl ribonucleoside1, the ribonucleoside triphosphate2and the ribonucleoside bisphosphate3of 6‐aminopyrazin‐2(1H)‐one are reported here. In aqueous solution, the ribonucleoside1was found to undergo acid‐ and base‐catalyzed rearrangement with an apparent half‐life ofca.63 h at neutral pH and 30°. The rearrangement appears to be specific acid‐ and base‐catalyzed. The thermodynamically most stable compound formed during this rearrangement reaction was isolated by HPLC and shown to be the β‐pyranosyl form4of the 6‐aminopyrazin‐2(1H)‐one nucleoside in its4C1chair conformation. This reactivity of1under physiological conditions may explain why Nature does not use this particular heterocyclic system to implement an acceptor

ISSN:0018-019X    

DOI:10.1002/hlca.19960790710

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractA 6‐aminopyrazin‐2(1H)‐one (pyADD), when incorporated as a pyrimidine‐base analog into an oligonucleotide chain, presents a H‐bond acceptor‐donor‐donor pattern to 5‐aza‐7‐deazaisoguanine (puDAA), the complementrary donor‐acceptor‐acceptor purine analog. Reported here are the syntheses of the phosphoramidite of the 2′‐deoxyribonucleoside bearing the puDAA base, oligonucleotides containing this nucleoside unit, the enzyme‐assisted synthesis of oligoribonucleotides containing the pyADD ribonucleoside, and the molecular‐recognition properties of this non‐standard base pair in an oligonucleotide context. A series of melting experiments suggests that the pyADD · puDAA base pair contributes to the relative stability of a duplex structure approximately the same as an A · T base pair, and significantly more than mismatches between these non‐standard bases and certain standard nucleobases. The pyADD nucleoside bisphosphate is accepted by T4 RNA ligase, but the triphosphate of the pyADD nucleoside was not incorported by T7 RNA polymerase opposite the puDAA nucleobase in a template. Oligonucleotides containing the pyADD base slowly undergo a reversible first‐order reaction, presumably an epimerization process to give the α‐D‐anomer. These experiments provide the tools for laboratory‐based use of the pyADD · puDAA base pair as a component of an oligonucleotide‐like molecular‐recog

ISSN:0018-019X    

DOI:10.1002/hlca.19960790711

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY