bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Characterization of DNA Fragments Bearing an Adenine Radiation Product: 7,8‐Dihydroadenin‐8‐one
Authors: Guy André , Duplaa Anne‐Marie , Harel Philippe , Téoule Robert 
Published: December 2004

AbstractThe 7,8‐dihydroadenin‐8‐one is one of the base derivatives formed by the action of ionizing radiation upon DNA. In order in investigate the mutagenic effects and the repair of DNA lesions induced by gamma rays, the synthesis of oligonucleotides bearing this damage has been performed by the phosphoramidite methodology. The preparation of the corresponding protected mononucleotide 6 (see Scheme) and its insertion into a DNA fragment are described. The modified oligonucleotide was purified by HPLC, characterized by DNA sequencing, enzymatic hydrolysis, and FAB mass spectrometry. In the experimental conditions used herein, no basic or acidic degradation was observed. In the DNA chain, the lesion is stable on piperidine heating under the usual DNA sequencing conditions.
Mammalian Alkaloids: O‐methylation of (S)‐ and (R)‐dideoxynorlaudanosoline‐1‐carboxylic acid by catechol O‐methyltransferase and identification of a yellow pigment obtained at physiological pH
Authors: Rozwadowska Maria Danuta , Chrzanowska Maria , Brossi Arnold , Creveling Cyrus R. , Bembenek Michael E. , Abell Creed W. 
Published: December 2004

AbstractO‐Methylation of optically active 3′,4′‐dideoxynorlaudanosoline‐l‐carboxylic acids 1 with O‐methyltransferase in vitro afforded almost exclusively the 7‐O‐methylated acids 3. A similar result was obtained with the yellow quinonemethide 4A obtained from 1 at neutral or slightly alkaline pH by oxidative decarboxylation and affording the 3,4‐dihydroisoquinoline 15 on methylation with catechol O‐methyltransferase (COMT). The structure of quinonemethide 4A was determined on the basis of spectral data, by its conversion into isoquinolines of established structure, and by synthesis. Quinonemethide 4A was found to be a weak inhibitor of monoamine oxidase A (MAO A) but not a substrate. Nonenzymatic oxidative decarboxylation of dopamine‐derived tetrahydroisoquinoline‐l‐carboxylic acids to quinonemethides may be a major factor in biochemical experimentation and should be considered in the interpretation of data.
Synthesis, Structure Elucidation, and Pharmacological Evaluation of 5‐Methyl‐oxymorphone (= 4,5α‐epoxy‐3,14‐dihydroxy‐5,17‐dimethylmorphinan‐6‐one)
Authors: Schmidhammer Helmut , Deeter Jack B. , Jones Noel D. , Leander J. David , Schoepp Darryle D. , Swartzendruber John K. 
Published: December 2004

AbstractSynthesis of 5‐methyl‐oxymorphone (3) was accomplished by oxidation of 5‐methylthebaine (4) with performic acid, followed by catalytic hydrogenation and cleavage of the 3‐MeO group. X‐Ray analysis confirmed that the 14‐OH group has, like the one in oxymorphone (1), β‐orientation. Pharmacological studies in vivo and in vitro showed 3 to possess slightly less opioid agonistic properties than 1.
Energy‐Minimized Structures and Calculated and Experimental Isomer Distributions in the Hexaaminecobalt(III) system [Co(trap)2]3+ (trap = 1,2,3‐propanetriamine)
Authors: Comba Peter , Hambley Trevor W. , Zipper Luc 
Published: December 2004

AbstractThe two isomers of [Co(trap)2]3+ (meso‐[Co(trap)2]3+ and rac‐[Co(trap)2]3+; trap = 1,2,3‐propanetriamine) have been studied by strain‐energy minimization. The two isomers have been separated preparatively by fractional crystallization, and fully characterized by 13C‐NMR and electronic spectroscopy, and microanalyses. The calculated isomer distribution (rac/meso = 60%: 40%) is in good agreement with HPLC analysis of thermodynamic equilibrium mixtures at 298 K and 353 K (rac/meso = 55% : 45%). These results are discussed in relation to the approach of calculating isomer distributions of hexaaminecobalt(III) systems by strain‐energy minimization neglecting the differences in environmental effects.
Sphinxolide, a 26‐Membered Antitumoral Macrolide Isolated from an Unidentified Pacific Nudibranch
Authors: Guella Graziano , Mancini Ines , Chiasera Giuseppe , Pietra Francesco 
Published: December 2004

AbstractIt is shown that an unidentified nudibranch of Hawaiian waters contains a 26‐membered macrolide, sphinxolide ((−)‐1) with potent activity against the KB cell line. The structure of sphinxolide, a 2:1 mixture of (E/Z)‐isomers at the formamide moiety, is established to be (–)‐1 on the basis of extensive NMR and FAB‐MS analysis, in combination with data for the products of mono‐ (→(−)‐2) and diacetylation (→(+)‐3).
Total Synthesis of L‐Allose, L‐Talose, and derivatives.
Authors: Auberson Yves , Vogel Pierre 
Published: December 2004

Abstract(1S, 4R, 5S, 6S)‐5‐exo, 6‐exo‐(Isopropylidenedioxy)‐7‐oxabicyclo[2.2.1]heptan‐2‐one ((−)‐1) was transformed with high stereoselectivity to L‐allose. Similarly, enantiomer (+)‐1 was transformed into L‐talose. The ketones (+)‐1 and (−)‐1 were derived from furan and 1‐cyanovinyl (1S)‐camphanate and 1‐cyanovinyl (1R)‐camphanate, respectively.
Eine neue Azepinring‐Synthese
Authors: Kvita Vratislav , Sauter Hanspeter , Rihs Grety 
Published: December 2004

A New Azepine‐Ring SynthesisA new one‐step synthesis of an azepine ring is described. The 2H‐pyran‐2‐one ring of methyl cumalate (8) or cumalaldehyde (2) upon reaction with an 1‐aminoacryl derivative, e.g. 1 or 6, is opened with subsequent decarboxylation to give a 1‐aminobutadiene derivative that undergoes an electrocyclic ring closure to the azepine ring (Schemes 1 and 2).
Direct Formation of a Substituted [5.5.5.5]Fenestrane by Intramolecular Arene‐Olefin Photocycloaddition
Authors: Mani Jürg , Schüttel Stefan , Zhang Cong , Bigler Peter , Müller Christian , Keese Reinhart 
Published: December 2004

AbstractIn a search for further synthetic routes to substituted [5.5.5.5] fenestranes, compound 1a, a derivative of 7‐methoxyindane, was photolyzed. Two of the three photoproducts, viz. the [3.5.5.5]fenestrane 3a and the isomer 4a, are formed according to the expected intramolecular meta‐cycloaddition. A different mechanism is suggested for the formation of the major component 2a.
Syntheses of Bile Pigments. Part 16. Synthesis of a vinyl‐substituted 2,3‐Dihydrobilinedione: Possible role of this new class of bile pigments in phycobilin biosynthesis
Authors: Gossauer Albert , Nydegger Fredy , Benedikt Eva , Köst Hans‐Peter 
Published: December 2004

AbstractThe total synthesis of racemic cis‐2,3,181, 182, ‐tetrahydroprotobiliverdin IXα dimethyl ester (19b), which is identical with the dimethyl ester of rac‐4, is described (Scheme 2). Under virtually neutral conditions, in solution, this bile pigment isomerized within a few min to racemic Z‐phycocyanobilin dimethyl ester (rac‐5b). Likewise, acid‐catalyzed allyl rearrangement of 3‐vinyl‐substituted cis‐ and trans‐2,3‐dihydrodipyrrin‐1(10H)‐ones 11c and 13c, respectively, yielded the corresponding ethylidene derivatives. In this case, however, the E‐isomer was formed stereo selectively from both substrates. The above results prove that, if protobiliverdin IXα (2) is transformed enzymatically to its 2,3,181, 182‐tetrahydro derivative, the latter would isomerize spontaneously to phycocyanobi‐lin. The biosynthesis of bacteriochlorophyll a and b from a common precursor bearing a vinyl group at C(8)may be straightforwardly explained in the same way.
Ferroelectric Liquid Crystals. Part 9. Laterally substituted phenyl benzoates incorporating a trans‐1,4‐disubstituted cyclohexane ring
Authors: Kelly Stephen M. 
Published: December 2004

AbstractAbout 65 diverse phenyl benzoates incorporating a trans‐1,4‐disubstituted cyclohexane ring and at least one lateral substituent have been synthesised. The dependence of the liquid‐crystal transition temperatures of these materials on various lateral substituents (F, Cl, CN, and Br) in different positions of the esters has been investigated systematically. The influence of up to four F‐atoms in various positions of a standard ester has been thoroughly studied and the optimum combination for a broad smectic C mesomorphic range established. In consequence, three homologous series incorporating the 4‐alkoxy‐2,3‐difluorobenzoic‐acid moiety were prepared. An additional CC bond was introduced into the alkyl chain attached to the cyclohexane ring of some of these esters and the resulting modifications of the transition temperatures determined. Three ester series incorporating a lateral substituent and the optically active (+)‐(S)‐(1‐methylheptyl)oxy substituent have also been synthesised, and similar effects have been observed. These materials can be used as important components of commercial chiral smectic C mixtures for electro‐optic display device applications.
A Novel Access to Ionone‐Type Compounds: (E)‐4‐oxo‐β‐ionone and (E)Oxo‐β‐irone via metal‐catalyzed intramolecular reactions of α‐diazo ketones with furans
Authors: Wenkert Ernest , Decorzant René , Näf Ferdinand 
Published: December 2004

Abstract(E)‐5‐Demethyl‐4‐oxo‐β‐ionone (2), (E)‐4‐oxo‐β‐ionone (3), (E)‐4‐oxo‐β‐irone (4), and the five‐membered ring analogs 36–41 were synthesized by a novel, convergent route starting from 2‐methylfuran (1). A recently discovered, intramolecular reaction of 2‐(diazoacyl)furans, catalyzed by dirhodium tetraacetate, leading to dienediones served as key step, thereby testing its utility in natural‐product synthesis for the first time.
Halochrome Molekeln 8. Mitteilung. Synthese und acidobasisches Verhalten von 3′‐substituierten 6,11‐Dihydrospiro[[1]benzopyrano[4,3‐b]indol‐6,9′−9′H‐xanthenen]
Authors: Gunzenhauser Sigmund , Balli Heinz 
Published: December 2004

Halochromic Molecules. Synthesis and Acidobasic Properties of 3′‐substituted 6,11‐dihydrospiro[[1]benzopyrano[4,3‐b]indol‐6,9′−9′9′H‐xanthenes]We have synthesized a series of 3′‐substituted 6,11‐ihydrospiro[6H‐chromeno[4,3‐b]indol–6,9′−9′H‐xanthenes] and one of their respective aza analogues. 1H‐MR data as well as the fragmentation in the mass spectra of starting and final products supported the postulated structures. With acid, the spiro compounds form ring‐opened intensely coloured xanthylium salts. UV/VIS spectra of these salts are listed and discussed. The ϵpH* curves in buffered MeOH/H2O solutions and the pK* values are determined. The title compounds could possibly be used in ‘pressure sensitive papers’.
Synthese von {2‐[3‐(2‐Ammonioethoxy)benzoyl]ethyl}‐trimethylammonium‐Bromid‐hydrobromid für die Affinitätschromatographie von Cholin‐Acetyltransferase (ChAT; EC 2.3.1.6)
Authors: Riggio Gaetano , Josef Raeber Alexander , Herbert Hopff Wolfgang 
Published: December 2004

Synthesis of {2‐[3‐(2‐Amonioethoxy)benzoyl]ethyl}trimethylammonium Bromide Hydrobromide for the Affinity Chromatography of Choline Acetyltransferase (ChAT; EC 2.3.1.6)ChAT is an essential enzyme that catalyzes the synthesis of acetylcholine from choline and activated acetic acid. For the affinity chromatography or biospecific adsorption, only those ligands are suited, which resemble the natural substrate. The ligands, however, cannot be bound directly to the matrix, but must be separated by a covalently bound spacer. Contrary to the often cited desorption by ionic gradients, we used the most specific desorption by the same ligand. The synthesis comprises seven steps starting from 3‐hydroxyacetophenon (7).
New fluorinating reagents. Part II. Preparation and Synthetic Application of a Saccharin Derived N‐Fluorosultam
Authors: Differding Edmond , Lang Robert W. 
Published: December 2004

AbstractThe synthesis of the new saccharin derived N‐fluorosultam 1 is described. A comparative study with commercially available N‐fluorosulfonamides shows 1 to be a superior fluorinating reagent for the synthesis of α‐fluorocarbonyl compounds.
Herstellung substituierter 1,6‐Methano[10]annulene durch Cycloadditionsreaktionen des 1H‐Cyclopropabenzols
Authors: Neidlein Richard , Kohl Matthias , Kramer Walter 
Published: December 2004

Synthesis of Substituted 1,6‐Methano[10]annulenes by Cycloadditions of 1H‐CyclopropabenzeneDiels‐Alder reactions of 1H‐cyclopropabenzene (1) with electron‐poor dienes, leading to substituted 1,6‐methano[10]annulenes, are described.
Structure and Thermal Behaviour of Methylcyclopentadiene Dimers
Authors: Thommen Walter , Pamingle Hervé , Schulte‐Elte Karl H. 
Published: December 2004

AbstractThe mixture of isomeric dimethyl‐endo‐tricyclo[5.2.1.02,6]deca‐3,8‐dienes (A) resulting from Diels‐Alder reactions of 1‐, 2‐, and 5‐methylcyclopenta‐1,3‐dienes (i–iii, respectively) at 20° was shown by GLC analysis to consist of at least 10 components (Table 1). The structures of the six major isomers 1–6, representing 96% of the total mixture, were established by 1H‐ and 13C‐NMR spectroscopy. Whereas on heating up to 110° the proportions of 1, 2, 4, and 6 remain nearly unaffected (±2 %), the dimers 3 and 5, formed in 22 % and 24 % yield, respectively, at 20°, isomerise above 70° reversibly via [3,3]‐sigmatropic rearrangement and equilibrate at 110° to a ca. 10:1 ratio.
An Electrochemical Variant in the Syntheses of Exaltone® and muscone: Anodic fragmentation of α, β‐unsaturated tosylhydrazones
Authors: Limacher Liviana L. , D. Delay François , Bédert Nicole , Tissot Paul 
Published: December 2004

AbstractRing enlargement of bicyclo[10.3.0]pentadec‐1(12)‐en‐13‐one p‐toluenesulfonylhydrazone into cyclopentadec‐4‐yn‐l‐one was accomplished under mild and controlled anodic oxidation conditions. The mechanism of this fragmentation is reconsidered.
Tilcotil® Studies [3+2] additions with isothiazol‐3(2H)‐one 1,1‐dioxide
Authors: Burri Kaspar F. 
Published: December 2004

AbstractDerivatives of isothiazol‐3(2H)‐one 1,1‐dioxide react regiospecifically with 1,3‐dipolar agents. The main regiocontrolling factor is ascertained to be the CO group of the dipolarophile. The topology of the adducts is also in general agreement with predictions based on perturbation theory. Several adducts can be aromatized to heterocyclic equivalents of saccharin, and may then be elaborated into structural analogs of tenoxicam (Tilcotil® and piroxicam (Feldene®)).
Synthesis of 8‐Aza‐2′‐deoxyadenosine and related 7‐Amino‐3H‐1,2,3‐triazolo[4,5‐d]pyrimidine 2′‐Deoxyribofuranosides: Stereoselective glycosylation via the nucleobase anion
Authors: Kazimierczuk Zygmunt , Binding Uwe , Seela Frank 
Published: December 2004

AbstractThe synthesis of 8‐aza‐2′‐deoxyadenosine ( = 7‐amino‐3H‐1,2,3 triazolo[4,5‐d]pyrimidine N3‐(2′‐deoxy‐β‐D‐ribofuranoside); 1) as well as the N2‐ and N1‐(2′‐deoxy‐β‐D‐ribofuranosides) 2 and 3 is described. Glycosylation of the anion of 7‐amino‐3H‐1,2,3‐triazolo[4,5‐d]pyrimidine (6) in DMF yielded three regioisomeric protected 2′‐deoxy‐β‐D‐ribofuranosides, i.e. the N3‐, N2‐, and N4‐glycosylated isomers 7 (14%), 9 (11%), and 11 (3%), respectively, together with nearly equal amounts of their α‐D‐anomers 8 (13%), 10 (12%), and 12 (4%; Scheme 1). The reaction became Stereoselective for the β‐D‐nucleosides if the anion of 7‐methoxy‐3H‐1,2,3‐triazolo[4,5‐d]pyrimidine (13) was glycosylated in MeCN: only the N3‐, N2, and N1‐(2′‐deoxy‐β‐D‐nucleosides) 14 (29%), 15 (32%), and 16 (23%), respectively, were formed (Scheme 2). NH3 Treatment of the methoxynucleosides 14–16 afforded the aminonucleosides 1–3. The anomeric configuration as well as the position of glycosylation were determined by combination of 13C‐NMR, 1H‐NMR, and 1D‐NOE difference spectroscopy. Compound 1 proved to be a substrate for adenosine deaminase, whereas the regioisomers 2 and 3 were not deaminated.
Novel cembranolides (Coralloidolide D and E) and a 3,7‐Cyclized cembranolide (Coralloidolide C) from the mediterranean coral Alcyonium coralloides
Authors: D'Ambrosio Michele , Guerriero Antonio , Pietra Francesco 
Published: December 2004

AbstractThe Mediterranean alcyonacean Alcyonium (= Parerytkropodium) coralhides (PALLAS, 1766) is shown to contain three novel diterpenes which are of biogenetic significance: the 3,7‐cyclized cembranoid Coralloidolide C ( = (+)‐(6R*, 7R*, 11S*, 12aS* 3aE)‐7,8‐epoxy‐3,5,6,7,8,9,10,11,12,12a‐decahydro‐12a‐hydroxy‐11‐isopropenyl‐1,4‐dimethyl‐3‐oxocyciopentacydoundecene‐8,6‐carbolactone; (−)‐3), the O‐bridged diketonic cembranolide Coralloidolide D (= (+)‐(1R*, 2S*, 3R*, 5R*, 12S*, 8Z)‐2,5‐epoxy‐1‐hydroxy‐12‐isopropenyl‐5,9‐dimethyl‐7,10‐dioxocyclotetradeca‐8‐ene‐1,3‐carbolactone; (+)‐4), and the diketonic epoxycembranolide coralloidolide E (=(+)‐(1R*, 2R*, 3R*, 12S*, 5Z, 8Z)‐1,2‐epoxy‐12‐isopropenyl‐5,9‐dimethyl‐7,10‐dioxocyclotetra‐deca‐5,8‐diene‐1,3‐carbolactone; (+)‐5), The latter in pyridine at r. t. undergoes a double bond shift from C(4) = C(5) to C(4) = C(18) to give the isomer (−)‐7. Structural assignments are mainly based on ID and 2D NMR and MS spectral data. Either corailoidolide A ((−)‐1) or the hypothetic unsaturated 1,4‐diketone 9 can be envisaged as the precursors of all coralloidolides.
Nucleotides. Part XXXI. Modified Oligomeric 2′–5′ A Analogues: Synthesis of 2′–5′ oligonucleotides with 9‐(3′‐azido‐3′‐deoxy‐β‐D‐xylofuranosyl)adenine and 9‐(3′‐amino‐3′‐deoxy‐β‐D‐xylofuranosyl)adenine as modified nucleosides
Authors: Herdewijn Piet , Charubala Ramamurthy , Pfleiderer Wolfgang 
Published: December 2004

AbstractA series of new 2′–5′ oligonucleotides carrying the 9‐(3′‐azido‐3′deoxy‐β‐D‐xylofuranosyl)adenine moiety as a building block has been synthesized via the phosphotriester method. The use of the 2‐(4‐nitrophenyl)ethyl (npe) and 2‐(4‐nitrophenyl)ethoxycarbonyl (npeoc) blocking groups for phosphate, amino, and hydroxy protection guaranteed straightforward syntheses in high yields and easy deblocking lo form the 2′–5′ trimers 21, 22, and 25 and the tetramer 23. Catalytic reduction of the azido groups in [9‐(3′‐azido‐3′‐deoxy‐β‐D‐xylofuranosyl)adenine]2′‐yl‐[2′‐(Op‐ammonio)→ 5′]‐[9‐(3′‐azido‐3′‐deoxy‐β‐D‐xylofuranosyl)adenin]‐2′‐yl‐[2′‐(Op‐ammonio)→ 5′]‐9‐(3′‐azido‐3′‐deoxy‐β‐D‐xylofuranosyl)adenine (21) led to the corresponding 9‐(3′‐amino‐3′‐deoxy‐β‐D‐xylofuranosyl)‐adenine 2′–5′ trimer 26 in which the two internucleotidic linkages are formally neutralized by intramolecular betaine formation.
Tordanone, un stéroïde replié avec une jonction de cycle A/B β‐cis (5β) et B/C α‐cis(8α)
Authors: Haag Thierry , Hetru Charles , Luu Bang 
Published: December 2004

Tordanone, a Twice Bent Steroid Structure with Ring A/B β‐cis(5β)‐ and Ring B/C α‐cis(8α)‐FusedThe 3β, 14α, 25‐trihydroxy‐5β, 8α‐cholestan‐6‐one ( = tordanone; 4) has been prepared by stereospecific hydrogenation of 3β, 14α, 25‐trihydroxy‐5β‐cholesta‐7,22ξ‐dien‐6‐one (5). This is the first stereospecific synthesis of a B/C cis‐fused steroid belonging to the 5β, 8α ‐cholestane group with a H‐atom at positions 5β (A/B cis‐fused) and 8α. The resulting twice bent structure shows a particularly strong steric hindrance of the β‐face where CH3(18) at the C/D ring junction and HβC(7) of the B ring are very close to each other. Structural features and mechanistic aspects of the hydrogenation are discussed.
Total synthesis of 2‐(β‐D‐ribofuranosyl)thiazole‐4‐carboxamide (Tiazofurin) and of precursors of ribo‐C‐nucleosides
Authors: Bimwala R. Mampuya , Vogel Pierre 
Published: December 2004

Abstract(1R,2S,4R)‐2‐Cyano‐7‐oxabicyclo[2.2.1]hept‐5‐en‐2‐yl (1S′)‐camphanate (5) was transformed into (−)‐methyl 2,5‐anhydro‐3,4,6‐O‐tris[(tert‐butyl)dimethylsilyl]‐D‐allonate (2), (+)‐1,3‐diphenyl‐2‐{2′,3′,5′‐O‐tris[(tert‐butyl)dimethylsilyl]‐β‐D‐ribofuranosyl}imidazolidine (3), and the benzamide 20 of 1‐amino‐2,5‐anhydro‐1‐deoxy‐3,4,6‐O‐tris‐[((tert‐butyl)dimethylsily)]‐D‐allitol. Compound 2 was converted efficiently into optically active tiazofurin (1).
The stereoselectivity of the alkylation of the dianion of ethyl 2‐hydroxy‐6‐methylcyclohexanecarboxylates: Control of stereochemistry at three adjacent stereogenic centers
Authors: Fráter Georg , Günther Wulf , Müller Urs 
Published: December 2004

AbstractYeast reduction of rac‐ethyl 2‐methyl‐6‐oxocylohexanecarboxylate (rac‐1) yielded selectively (+)‐ethyl 2‐hydroxy‐6‐methylcyclohexane carboxylate (+)‐2 (Scheme 1) which has been alkylated with 5‐iodo‐2‐methylbut‐2‐ene by (the dianion method to furnish the 4‐methylbut‐3‐enyl derivat 3 (Scheme 3)). NaBH4 reduction of (+)‐1 led to three hydroxy‐carboxylates (−)‐2, (+)‐5, and (−)‐6 (Scheme 4). Allylation of the dianion of (+)‐5 afforded (+)‐7.
Mammalian Alkaloids: O‐Methylation of (±)‐Norcoclaurine‐1‐carboxylic Acid and Related Isoquinolines Including (S)‐ and (R)‐Norcoclaurine with 14C‐Labeled S‐Adenosyl‐L‐Methionine in Presence of Mammalian Catechol O‐Methyltransferase
Authors: Sekine Yasuo , Crevelling Cyrns , Bell Maureen , Brossi Arnold 
Published: December 2004

Abstract(±)‐Norcoclaurine‐1‐carboxylic acid (5) and the derived dihydroisoquinolinone 6 (present as quinonemethide 6a at pH 7) afforded, on methylation with 14C‐labeled S‐adenosyl‐L‐methionine in the presence of mammalian catechol O‐methyltransferase, exclusively the 7‐O‐methylated congeners 7 and 9, respectively. High stereoselectivity of the O‐methylation was observed with (−)‐(S)‐ and (+)‐(R)‐norcoclaurine (2a and 2b, resp.), affording 80% of 6‐O‐methylated isoquinoline 12 and 20% of the 7‐O‐methylated isomer 11 from 2a, and the reversed proportion of 12 and 11 from 2b. Synthesis of the reference amino acid 8 was achieved by Pictet‐Spengler condensation of O‐benzyl‐protected dopamine 17 with benzyl‐protected keto acid 20 (→ 21) followed by methylation with diazomethane (→22 + 23) and removal of the protecting groups by acid hydrolysis. It is considered unlikely that amino acids such as 5 constitute important precursors in the biosynthesis of isoquinolines related to reticuline.
A Theoretical Investigation of Enantioselectivity: Michael Reaction of Secondary Enamines with Enones
Authors: Sevin Alain , Masure Daniel , Giessner‐Prettre Claude , Pfau Michel 
Published: December 2004

AbstractA theoretical study of the enantioselective Michael‐type addition of chiral secondary enamines to enones has been achieved. In a first step, the structures of various free enamines have been investigated at the ab initio and MNDO levels. The results clearly show that upon substitution of the prototype vinylamine, the N‐center is pyramidalized. The study of enamines with chiral N‐substituents such as (S)‐Ph(Me)CH or (S)‐cyclohexyl(Me)CH reveals a very complex pattern, where up to 8 local energy minimums are characterized whose examination shows that no prediction can be. done regarding the final enantioselectivity of their reaction with enones. These sets of conformers can be regarded as nearly energetically degenerate, at least for the three or four ones of lowest energy. The study of the compact complexes formed between the latter optimal conformers and acrylaldehyde shows that: (i)syn complexation with respect to the N lone pair is the only one which remains possible for steric reason, (ii) small geometrical rearrangements take place as the complexation proceeds, (iii) no clear‐cut correspondence exists between the relative sequence of the low‐energy conformers of the free enamines and the sequence of the low‐energy complexes, (iv) the examination of the relative gradients of the complexation energies provides an index for predicting the relative facilities of the enantiometric pathways, in good agreement with the experimental facts. Our study emphasizes the great complexity of systems of realistic size and brings about critical conclusions regarding classical ad hoc models.