摘要:

AbstractReaction of the triolide1from (R)‐3‐hydroxybutanoic acid withLawesson's reagent5leads to the mono‐, di‐, and trithio derivatives6–8which can be isolated in pure form (20–40% yields), and which have crystal structures very similar to the parent triolide1(Fig. 1). Similarly, pentolide3is converted to mixtures of various thio derivatives, three of which are separated (10–12) by HPLC and fully characterized. The X‐ray structures of the mono‐ and of one of the dithiopentolides (10, 12) differ remarkably from each other (Fig. 3). Reduction of the thiotriolides6–8(NaBH4, R3SnH, Cl3SiH,Raney‐Ni) gives 12‐membered rings containing up to three ether groups (chiral crown ethers,15, 17–19) in poor yields. The thiotriolides react spontaneously and in yields of up to 96% with ammonia, certain primary amines, and hydroxylamine to give imine and oxime derivatives with intact 12‐membered‐ring backbones (20, 22–24, 30, see crystal structures inFigs. 4–7). The rigid structure of all the derivatives of triolide1puts the CO, CS, and CNR O‐, S‐, and N‐atoms in juxtaposition (a feature reminiscent of the side chains in the iron‐binder enterobactin,Fig. 6). Imines containing PPh2groups are prepared (30, 33, 35) from the thiotriolides and tested as chiral ligands for PdII‐catalyzed 1,3‐diphenyallylations (→37, enantiomer ratio up to 77:23). The reactions described demonstrate that multiple reactions of the triolide1from (R)‐3‐hydroxybutanoic acid which proceed through tetrahedral intermediates are possible without ring opening – the skeleton is remarkably stable, and this might be exploited as a template for bringing up to three pendent substituents into close proximity to allow a study of their interactions and cooperative properties. Also, the di‐ and trithio derivatives7and8could be use

ISSN:0018-019X    

DOI:10.1002/hlca.19960790202

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractThe mycalamides (3) and related natural products contain an α‐hydroxy acid1boundviaan amide bond to an α‐alkoxy amine. The high density of functional groups in the ‘coupling region’ renders the coupling reactions delicate. Model studies showed that an alternate assembly of the molecular halves is possible using an ‘Umpolung’ of an α‐alkoxy isocyanate,e.g.13. Thus, combination of the ester12with13led to the α‐keto amide16. The further elaboration of16to the α‐hydroxy‐amide structure found in the

ISSN:0018-019X    

DOI:10.1002/hlca.19960790203

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractWe used semi‐empirical andab initiocalculations to investigate the nucleophilic attack of the OH−ion on the β‐lactam carbonyl group. Both allowed us to detect reaction intermediates pertaining to proton‐transfer reactions rather than the studied reaction. We also used the PM3 semi‐empirical method to investigate the influence of the solvent on the process. The AMSOL method predicts the occurrence of a potential barrier of 20.7 kcal/mol due to the desolvation of the OH−ion in approaching the β‐lactam carbonyl group. Using the supermolecular approach and a H2O solvation sphere of 20 molecules around the solute, the potential barrier is lowered to 17.5 kcal/mol, which is very close to the experimental value

ISSN:0018-019X    

DOI:10.1002/hlca.19960790204

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractChemical screening of the secondary metabolites fromHalenia corniculataL. (CORNAZ), by LC/UV,LC/TSP‐MS (thermospray), and LC/ES‐MS (electrospray) was used for the targeted isolation of corniculoside (1), a new biosidic ester secoiridoid. The structure was established as 7‐β‐[(E)‐4′‐O‐(β‐D‐glucopyranosyl)caffeoyloxy]‐sweroside by 1D‐ and 2D‐NMR, LC/UV, LC/MS, and FAB‐MS data, in combin

ISSN:0018-019X    

DOI:10.1002/hlca.19960790205

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractAddition reactions of organometallic reagents with 4,4‐disubstituted 1,3‐thiazole‐5(4H)‐thiones were studied. Whereas the reactions with alkyllithium and alkylGrignardreagents occurred in the thiophilic manner, the carbophilic addition was observed with allyllithium and allylGrignardreagents. A radical reaction mechanism is proposed for rationalizing these observations (Scheme 5). A radical cyclization of the prepared 5‐allyl‐4,5‐dihydro‐1,3‐thiazole‐5‐thiol derivatives yielded 1,6‐dithia‐3‐azaspi

ISSN:0018-019X    

DOI:10.1002/hlca.19960790206

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractThree new saponins1–3were isolated fromHerniaria glabraby means of prep. HPLC and TLC. The structures were established mainly by a combination of 2D‐NMR techniques (COSY, TOCSY, ROESY, HMQC, and HMBC) asO‐α‐L‐rhamnopyranosyl‐(1→4)‐O‐β‐D‐glucopyranosyl‐(1‐→6)‐O‐[β‐D‐glucopyranosyl‐(1→2)]‐β‐D‐glucopyranosyl medicagen‐28‐ate (herniaria saponin 4;1),O‐β‐D‐glucopyranosyl‐(1→3)‐O‐α‐L‐rhamnopyranosyl‐(1→2)‐O‐[β‐(3R)‐D‐apiofuranosyl‐(1→3)]‐β‐D‐4‐O‐acetylfucopyranosyl 3‐O‐(β‐D‐glucuronopyranosyl)‐16α‐hydroxymedicagen‐28‐ate (herniaria saponin 5;2), andO‐α‐L‐rhamnopyranosyl‐(1

ISSN:0018-019X    

DOI:10.1002/hlca.19960790207

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractStereocontrolled addition of alk‐1‐enylmetal reagents to the chiral (alkoxymethyl)‐substituted acylsilanes (±)‐6gave rise to α‐silylated allyl alcohols, which were converted to the corresponding acetates or propionates11–16(Scheme 2). Deprotonation and silylation with Me3SiCl afforded – in anIrelandester‐enolate‐acceleratedClaisenrearrangement – stereoselectively αδ‐silylated γδ‐unsaturated carboxylic acids18–24(Scheme 4). The Me3Si groups in α‐position to the COOH group of these compounds were removed chemoselectively in presence of the chiral silyl group in δ‐position by treatment with Bu4NF · 3 H2O or Et3N · 3 HF (→27–32;Scheme 5). The reaction sequence allows a novel stereocontrolled access to chiral C‐frameworks possessing a vinyls

ISSN:0018-019X    

DOI:10.1002/hlca.19960790208

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractThe syntheses of various fluorocarbon/fluorocarbon and fluorocarbon/hydrocarbonrac‐1,2‐ and 1,3‐di‐O‐alk(en)ylglycerophosphocholines andrac‐1,2‐di‐O‐alkylglycerophosphoethanolamines (seeFig.2), which may be used as components for drug‐carrier and delivery systems, are described together with some results concerning their biological tolerance. They were obtained by phosphorylation of perfluoroalkylatedrac‐di‐O‐alk(en)ylgly‐cerols using POCl3, then condensation with choline tosylate orN‐Boc‐ethanolamine (2‐[(tert‐butoxy)carbonyl‐amino]ethanol) followed by Boc‐deportection (Schemes 6–8). The fluorcarbon/fluorocarbon 1,2‐di‐O‐alkylgly‐cerols were prepared byO‐alkylation ofrac‐1‐O‐benzylglycerol using perfluoroalkylated mesylates, then hydrogenolysis for benzyl deprotection (Scheme 1). The two different hydrophobic chains in the mixed fluorocarbon/fluorocarbon and fluorocarbon/hydrocarbon 1,2‐di‐O‐alk(en)ylglycerols were introduced starting from 1,2‐O‐iso‐propylidene‐ thenO‐trityl‐protected glycerols or from 1,3‐O‐benzylidene‐glycerol (Schemes 3and4). The perfluoroalkylatedO‐alkenylglycerols were obtained byO‐alkylation of a glycerol derivative using an ω‐unsaturated alkenyl reagent, the perfluoroalkyl segment being connected onto the double bond in a subsequent step (Schemes1) and3. The perfluoroalkylated symmetrical and mixed 1,3‐di‐O‐alkylglycerols were synthesized by displacement of the Cl‐atom in epichlorohydrin by perfluoroalkylated alcohols, then catalytic (SnCl4) opening of the oxirane ring of the resulting alkyl glycidyl ethers in neat alcohols (Scheme 5). When injected intravenously into mice, acute maximum tolerated doses higher than 1500 and 2000 mg/kg body weight were

ISSN:0018-019X    

DOI:10.1002/hlca.19960790209

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractThe application of the improved phosphoramidite strategy for the synthese of oligonucleotides using β‐eliminating protecting groups to phospholipid chemistry offers the possibility to synthesize phospholipid conjugates of AZT (6) and cordycepin. The synthesis of 3′‐azido‐3′‐deoxythymidine (6) was achieved by a new isolation procedure without chromatographic purification steps in an overall yield of 50%. Protected cordycepin ( = 3′‐de‐oxyadenosine) derivatives, theN6,2′‐bis[2‐(4‐nitrophenyl)ethoxycarbonyl]cordycepin (12) and theN6,5′‐bis[2‐(4‐nitrophenyl)ethoxycarbonyl]cordycepin (13) wre prepared by known methods and direct acylation ofN6‐[2‐(4‐nitrophenyl)ethoxycarbonyl]cordycepin (9), respectively. These protected nucleosides and the 3′‐azido‐3′‐de‐oxythymidine (6) reacted with newly synthesized and properly characterized lipid‐phosphoramidites21–25, catalyzed by 1H‐tetrazole, to the corresponding nucleoside‐phospholipid conjugates26–38in high yield. The deprotection was accomplishedviaβ‐elimination with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) in aprotic solvents to give analytically pure nucleoside‐phospholipid diesters39–51as triethylammonium or sodium salts. The newly synthesized

ISSN:0018-019X    

DOI:10.1002/hlca.19960790210

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY

摘要:

AbstractFrom the ciliateEuplotes focardii, collected from Ross Sea coastal waters, Antarctica, a new‐skeleton diterpenoid, epoxyfocardin, was isolated as a 85:15 mixture of hemiacetals8aand8b. The absolute configuration of8a/8bwas determined fromMosher's esters11a/11band12a/12b. Focardin9a/9b, most likely a biogenetic precursor of8a/8b, was also isolated as a minor component. Focardin, and particularly epoxyfocardin, proved to be toxic towards representatives of ciliate communities from Antarctic, temperate, tropical, and equatorial environments, constituting the first example of ecologically relevant metabolites from ciliate species that inhabit polar ecosystem

ISSN:0018-019X    

DOI:10.1002/hlca.19960790211

出版商:WILEY‐VCH Verlag GmbH    

年代:1996

数据来源: WILEY