ISSN:0018-019X    

DOI:10.1002/hlca.19960790502

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractThe natural genesis of life on Earth is a hypothesis of evolutionary science; it is the task of synthetic organic chemistry to test this hypothesis experimentally. The aim of an experimental aetiological chemistry is not primarily to delineate the pathways along which our (‘natural’) life on Earthcouldhave originated, but to provide decisive experimental evidence, through the realization of model systems (‘artificial chemical life’), that lifecanarise as a result of the organization of organic

ISSN:0018-019X    

DOI:10.1002/hlca.19960790503

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractNinety years ago, chemical methods were used in solving biological problems. In our days, methods of evolutionary biology are going to be used in solving problems of synthetic chemistry.

ISSN:0018-019X    

DOI:10.1002/hlca.19960790504

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractThe cellobiose‐derived dialkynes14and15were prepared by glycosidation of the acceptor9with the thioglycosides12(82%) and13(85%), respectively. The acceptor9was prepared from the known alcohol2viathe lactone7in five steps (48% overall), and the donors12and13were prepared from the alkynylated anhydroglucose derivative10(60% overall). Acetolytic debenzylation of14and15(→16and17, resp.) followed by deacylation of16yielded 60% of the cellobiose‐derived dialkyne18. Deacylation of14(→19), methoxymethylation (→20) and trimethylgermylation led to the orthogonally protected dialkyne21(69% overall). Protodesilylation of21with K2CO3/MeOH gave22(90%), while the Me3Ge group was selectively removed with CuBr (19 mol‐%) in THF/MeOH to give20(95%). Treatment of21with aqueous HCl solution led to19(80%). Bromodegermylation of21(NBS/AgOOCCF3) led to a mixture of23(85%) and24(11%). Similar conditions using CuBr instead of AgOOCCF3gave exclusively the bromoalkyne23(93%). The temperature dependence of the δ values of the OH resonances of18in (D6)DMSO evidence a strong intramolecular H‐bond between C(

ISSN:0018-019X    

DOI:10.1002/hlca.19960790505

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractAn asymmetric synthesis of the spermidine alkaloid (+)‐cyclocelabenzine (1a) and its (−)‐(13S)‐epimer1bis described using optically active (+)‐(3S)‐3‐amino‐3‐phenylpropionic acid as the chiral building block. The isoquinolin‐1‐one fragment15was synthesized by a modifiedBischler‐Napieralskireaction. The relative configuration of the (−)‐isomer was determined by an X‐ray crystal‐structure analysis, which enabled us to determine the absolute configurati

ISSN:0018-019X    

DOI:10.1002/hlca.19960790506

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractIn order to trap ‘thiocarbonyl‐aminides’A, formed as intermediates in the reaction of thiocarbonyl compounds with phenyl azide, a mixture of 2,2,4,4‐tetramethyl‐3‐thioxocyclobutanone (1), phenyl azide, and fumarodinitrile (8) was heated to 80° until evolution of N2ceased. Two interception products of the ‘thiocarbonylaminide’A(ArPh) were formed: the known 1,4,2‐dithiazolidine3(cf. Scheme 1) and the new 1,2‐thiazolidine12(Scheme 2). The structure of the latter was established by X‐ray crystallography (Fig.1). The analogous ‘three‐component reaction’ with dimethyl fumarate (9) yielded, instead of8, in addition to the known interception products3and6(Scheme 1), two unexpected products15and16(Scheme 3), of which the structures were elucidated by X‐ray crystallography (Fig.2). Their formation is rationalized by a primary [2 + 3] cycloaddition of diazo compound18with1to give19, followed by a cascade

ISSN:0018-019X    

DOI:10.1002/hlca.19960790507

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractA series of novel open‐chain and cyclic conformationally constrained α,α‐disubstituted (R)‐ and (S)‐glycine derivatives (‘α‐chimeras’) combining side chains of Asp, Glu, Leu, Phe, Ser, and Val have been efficiently synthesized by using α‐alkylation of racemic 4‐monosubstituted 2‐phenyl‐1,3‐oxazol‐5(4H)‐ones of type5, resolution after reaction with (S)‐phenylalanine cyclohexylamide (8) as chiral auxiliary, a novel azlactone/dihydrooxazole interconversion reaction to synthesize optically pure α‐substituted (R)‐ and (S)‐serine derivatives coupled with succinimide‐ring formation of aspartic‐acid derivatives. Based on X‐ray structures of (R,S)‐9b, (R,S)‐11c, (R,S)‐18, and (S,S)‐30, the absolute configuration of these novel amino‐acid building blocks could be unambiguously determined and their preferred conformations in the crystalline state be assessed. The high preference of the open‐chain derivatives (R,S)‐1, (S,S)‐3, and (R,S)‐11cfor β‐turn type‐I conformations, as well as of the succinimide derivatives (R,S)‐2, (S,S)‐19, (S,S)‐24, (S,S,S)‐26, and (R,S)‐29for β‐turn type‐II conformations and of (S,S)‐4, (R,S)‐18, (R,S)‐23, and (S,S)‐30for β‐turn type‐II′ conformations could be confirmed in solution by using CD and NMR spectroscopy. Finally, the spiro derivatives (R,S)‐29and (S,S)‐30incorporating the ‘α‐chimera’ of Asp/Glu constitute

ISSN:0018-019X    

DOI:10.1002/hlca.19960790508

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractTheCinchonaalkaloid analogs (+)‐ and (−)‐5with a quinuclidine‐2‐methanol residue attached to C(2) of a 9,9′‐spirobifluorene moiety were prepared as a racemic mixture by reacting lithiated 2‐bromo‐9,9′‐spirobifluorene7with (2‐ethoxycarbonyl)quinuclidine (±)‐6to give ketone (±)‐8, followed by diastereoselective reduction with diisobutylaluminum hydride (DIBAL‐H). The absolute configuration at C(9) and C(8),i.e., at the methanol bridge and the adjacent quinuclidine C‐atom, in the two enantiomers of5is identical to the configuration at the corresponding centers in (−)‐quinine (1) and (+)‐quinidine (2), respectively. For the optical resolution of (±)‐5, a chiral stationary phase for HPLC was prepared by covalently bonding quinineviaa thiol spacer to a silica‐gel surface. The enantiomer separation was accomplished at an α value of 1.61 with (±)‐5being eluted last, in agreement with1H‐NMR studies in CDCl3which showed that (+)‐5underwent a more stable host‐guest association with quinine than (−)‐5.1H{1H} NuclearOverhausereffect (NOE) difference spectroscopical analysis of the host‐guest associations with quinine in CDCl3, combined with computer‐model examinations, allowed the assignment of the absolute configurations as (+)‐(8R,9S)‐5and (−)‐(8S,9R)‐5. A detailed conformational analysis displayed excellent agreement between the results of computational methods (Monte Carlo multiple minimum simulations, analyses of the total energy as a function of the flexible dihedral angles in the molecule) and1H{1H}‐NOE difference spectroscopical data. It was found that (−)‐5and (+)‐5differ significantly in their conformational preference from their natural counterparts quinine (1) and quinidine (2). Whereas the natural alkaloids prefer the ‘open’ conformation, with the quinuclidine N‐atom pointing away from the quinoline ring, analog (±)‐5adopts preferentially (byca.4 kcal mol−1) a ‘closed’ conformation, in which the quinuclidine N‐atom points into the cleft of the 9,9′‐spirobifluorene moiety. Since the basic quinuclidine N‐atom in the ‘closed’ conformation is sterically shielded from forming strong H‐bonds, t

ISSN:0018-019X    

DOI:10.1002/hlca.19960790509

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractThe methanolysis of the epimeric 7‐chloro‐7H‐yohimbine derivatives2and3was reinvestigated. In case of the 7α‐epimer2, the reaction was uneventful and conformed with earlier observations,i.e., under sufficiently mild conditions, only the imino ether4(= imino ether A) was produced. Under the same conditions, the less reactive β‐isomer3furnished a mixture of both imino ethers4and5, accompanied by the elimination product11, and by equal amounts of yohimbine (1) and 3,4,5,6‐tetradehydroyohimbine (12), which are believed to arise through a disproportionation process of the putative intermediate 5,6‐didehydroyhimbine (23). The nature of this divergent reactivity and of the ready equilibration of4and5was investigated by means of extensive force‐field and semi‐empirical calculations (AM1 and PM3) of various conformers of the compounds2–5and of some possible r

ISSN:0018-019X    

DOI:10.1002/hlca.19960790510

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractThis paper presents a short synthesis of oncinotin‐11‐one (11), a minor alkaloid ofOncinotis tenuiloba(Apocynaceae). Based on a disconnection approach, the spermidine portion of the key intermediate6was constructed consecutively by simpleN‐alkylations starting from ethyl piperidine‐2‐carboxylate (1). Treatment of6within situlithiated 2‐[(10‐bromodecyl)oxy]tetrahydropyran resulted in the formation of the keto moiety under simultanous deprotection of the lactam N‐atom to give the amino ketone7in 71% yield. Cleavage of the tetrahydro‐2H‐pyran‐2‐yl(Thp) portion andJonesoxidation of the resulting alcohol8gave the amino acid9which was cyclized. FinalN‐debenzylation of10provided the natural alkaloid11. Only two protective groups were needed in this synthesis. The reaction ofN‐alkyl‐lactams with organom

ISSN:0018-019X    

DOI:10.1002/hlca.19960790511

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY