bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthese von 4‐Benzylthio‐ und 4‐(Arylthio)‐1,3‐oxazol‐5(2H)‐onen
Authors: Wipf Peter , Prewo Roland , Jost H. Bieri , Heimgartner Heinz , Nastopoulos Vassilios , Germain Gabriel 
Published: December 2004

Synthesis of 4‐(Benzylthio)‐and 4‐(Arylthio)‐1,3‐oxazole‐5(2H)‐onesFollowing a known procedure, 4‐(benzylthio)‐1,3‐oxazol‐5(2H)‐one (4a) was synthesized starting from sodium cyanodithioformate (1) and cyclohexanone (Scheme 1). The structure of the intermediate 4‐(benzylthio)‐1,3‐thiazol‐5(2H)‐one (3a) was established by X‐ray crystallography. An alternative route was developed for the synthesis of 4‐(arylthio)‐1,3‐oxazol‐5(2H)‐ones which are not accessible by the former reaction. Treatment of ethyl cyanoformate (5) with a thiophenol in the presence of catalytic amounts of Et2NH and TiCl4, followed by addition of a ketone and BF3.Et2O in a one‐pot‐reaction, gave 4f–i in low‐to‐fair yields (Scheme 3). Both synthetic pathways‐complementary as for benzyl–S and aryl‐S derivatives–seem to be limited with respect to variation of substituents of the ketone.
Determination of the Quantum Yield of Intersystem Crossing of Rose Bengal
Authors: Murasecco‐Suardi Patricia , Gassmann Ernst , Braun André M. , Oliveros Esther 
Published: December 2004

AbstractThe quantum yield of intersystem crossing (Φisc) of a sensitizer is related to the quantum yield of singlet‐oxygen production (Φ(1O2)) by the efficiency of the energy transfer (φet) and is an important parameter in the evaluation of potential applications of sensitized photo‐oxidations. Using two different laser photolysis techniques, the energy‐transfer method and the partial saturation method, Φisc of rose bengal has been determined in MeOH and in aqueous solutions. The results confirm that with Φisc(H2O) = 1.05(± 0.06) and Φisc(MeOH)=0.90(±0.08), the generally assumed relation Φisc · φet = Φ(1O2), with φet = 1, cannot be maintained any longer (Φ(1O2, H2O) = 0.75 and Φ(1O2, MeOH) = 0.76). During these experiments, a second intermediate has been observed which is produced from the triplet state of rose bengal and, stabilized in a anionic micellar solution, has been shown to be the radical cation of the sensitizer. The efficiency of the electron transfer has been evaluated from transient absorption and bleaching recordings, and it seems conclusive to attribute the results to the difference between Φisc and Φ(1O2).
Horeau's Coupling of Enantiomers Revisited. The Reversible Coupling of Enantiomers to Form Diastereoisomers in Kinetically Labile Metal Complexes
Authors: Marty Werner , Pasquier Maurice L. , Gampp Harald 
Published: December 2004

AbstractPairs of enantiomeric molecules (ℜ︁,𝔖) of a substrate of unknown, but incomplete enantiomeric purity may be coupled to each other through labile coordination to a metal center M. This results in the formation of an equilibrium mixture of diastereoisomeric complexes, viz. meso‐LnMℜ︁𝔖(=m) and a pair of enantiomers LnMℜ︁ℜ︁ and LnM𝔖𝔖(= e), where L is an achiral auxiliary ligand. General expressions are presented for determining the ratio of enantiomers [ℜ︁]0/[𝔖]0 from experimental parameters, which may be obtained from NMR measurements. Effects of diastereoselectivity are specifically considered. Limiting cases (nearly pure or nearly racemic substrates, very high or no diastereoselectivity, very large or no excess of free substrate) are discussed. The cases of additional diastereoisomerism owing to different coordination geometries and of the formation of complexes with more than two substrate molecules per metal center are also investigated. The results presented can not only be used for determining the enantiomeric excess but also for designing optimal strategies for the successive resolution of partly enriched samples.
Regioselective Electrophilic Additions of Bicyclo[2.2.n]alk‐2‐enes Controlled by Remote Epoxide Functions
Authors: Claret François , Carrupt Pierre‐Alain , Vogel Pierre 
Published: December 2004

AbstractThe electrophilic additions of 2‐nitrobenzenesulfenyl chloride to (1RS,2SR,4RS)‐spiro[bicyclo[2.2.1]hept‐5‐ene‐2,2′‐oxirane] (12) and (1RS,2SR,4RS)‐spiro[bicyclo[2.2.2]oct‐5‐ene‐2,2′‐oxirane] (14) were not regioselective under condition of kinetic control. However, good regioselectivity was observed for the addition of 2‐nitro‐benzenesulfenyl chloride to (1RS,2RS,4RS)‐spiro[bicyclo[2.2.1]hept‐5‐ene‐2,2′‐oxirane] (13), giving (1RS,2SR,4SR,5RS,6RS)‐6‐exo‐(2‐nitrophenylthio)spiro[bicyclo[2.2.1]heptane‐2.2′‐oxirane]‐5‐endo‐yl chloride (24) and for the exo addition to (1RS,2RS.4RS)‐spiro[bicyclo[2.2.2]oct05‐ene‐2,2′‐oxirane] (15), giving preferntially (1RS,2SR,4SR,5RS,6 RS)‐6‐exo‐(2‐nitrophenylthio) spiro[bicyxlo[2.2.2]octane‐2,2′‐oxirane]‐5‐endo‐yl chloride (30). The facial selectivity (electrophilic exo vs. endo attack on the bucyclic alkene) depended on the relative configuration of the spiroepoxide ring in the bicyclo[2.2.2]octenes 14 and 15. The exo‐epoxide 14 was attacked preferentially (6:1) on the endo face by sulfenyl whereas exo attack was preferred (7:2) in the case of the endo‐epoxide 15. No products resulting from transannular ring expansion of the spiro‐epoxide moieties could be detected.
Isolierung von 10′‐Apo‐β‐carotin‐10′‐ol und (3R)‐10′‐Apo‐β‐carotin‐3,10′‐diol (Galloxanthin) aus Rosenblüten. 5. Mitteilung über Rosenfarbstoffe
Authors: Märki‐Fischer Edith , Eugster Conrad Hans 
Published: December 2004

Isolation of 10′‐Apo‐β‐carotene‐10′‐ol and (3R)‐10′‐Apo‐β‐carotene‐3,10′‐diol (Galloxanthin) from Rose FlowersThe novel (all‐E)‐10′‐apol‐β‐carotene‐10′‐ol (2) and (all‐E,3R)‐10′‐apo‐β‐carotene‐3,10′‐diol (5) have been isolated from petals of one yellow species and various whitish or yellow blend varieties of rose cultivars. Each (all‐E)‐compound is accompanied by a (Z)‐isomer, probably the (9Z)‐isomer. Diol 5 proved to be identical with galloxanthin, an apo‐10′‐carotenol previously isolated from the retina of chicken.
Sarcodictyin A and Sarcodictyin B, Novel Diterpenoidic Alcohols Esterified by (E)‐N(1)‐Methylurocanic Acid. Isolation from the Mediterranean Stolonifer Sarcodictyon roseum
Authors: D'Ambrosio Michele , Guerriero Antonio , Pietra Francesco 
Published: December 2004

AbstractThe Mediterranean stolonifer Sarcodictyon roseum (= Rolandia rosea) (Cnidaria, Anthozoa, Alcyonaria, Stolonifera, Clavulariidae) is shown to contain two novel diterpenoidic alcohols esterified by (E)‐N(1)‐methyl‐urocanic acid (= E)‐3‐(l‐methyl‐lH‐imidazol‐4‐yl)acrylic acid). They are sarcodictyin A ( = (−)‐(4R,4a,R, 7R,10S,11S,12aR,lZ,5E,8Z)‐7,10‐epoxy‐3,4,4a,7,10,11,12,12a‐octahydro‐7‐hydroxy‐6‐(methoxycarbonyl)‐1,10‐dimethyl‐4‐(1‐methylethyl)benzocyclodecen‐11‐yl (E)‐3‐(1‐methyl‐lH‐imidazol‐4‐yl)acrylate; (−)‐1) and sarco‐dictyin B (the 6‐(ethoxycarbonyl analogue; (−)‐2). The assignment of the structures is mainly based on 1D‐ and 2D‐NMR data, as well as on chemical transformations of (−)‐1, such as transesterification with MeONa/MeOH giving methyl (E)‐N(1)‐methylurocanate (3) and the free alcohol (+)‐4 and reduction with LiAlH4 followed by benzoylation giving dibenzoate 7. Absolute configurations are based on Horeau's method of esterification of (+)‐4.
Azidinium‐Salze. 23. Mitteilung. Photolyse heterocylischer Azidinium‐Salze
Authors: Balli Heinz , Huys‐Francotte Martine , Schmidlin Fred 
Published: December 2004

Photolysis of Heterocyclic Azidinium SaltsThe photochemistry of some azidinium salts was investigated. Their photolusis led to a large variety of products which were isolated and identified. Reaction mechanisms involving singlet and triplet nitrene intermediates are discussed to explain the product formation.
L‐Carnitine. Novel Synthesis and Determination of the Optical Purity
Authors: Voeffray Robert , Perlberger Jean‐Claude , Tenud Leander , Gosteli Jacques 
Published: December 2004

AbstractA new route to L‐carnitine (1) based on the resolution of th trimethylammonium derivative 5 is described. The enantiomeric purity of 1 is determined by 1H‐NMR of its O‐acetyl hydrochloride 11 using [Eu(hfc)3] as chiral shift reagent. The optical rotation of 1 with an enantiomeric purity ≥99% is [α] =−31.3° (c = 10, H2O).
Reactions of Chiral 2‐(tert‐Butyl)‐2H,4H‐1,3‐dioxin‐4‐ones Bearing Functional Groups in the 6‐Position and Diastereoselective Catalytic Hydrogenation to cis‐2,6‐Disubstituted 1,3‐Dioxan‐4‐ones
Authors: Noda Yoshihiro , Seebach Dieter 
Published: December 2004

Abstract(R)‐5‐Bromo‐6‐(bromomethyl)‐2‐(tert‐butyl)‐2H,4H‐1,3‐dioxin‐4‐one (2) derived from (R)‐3‐hydroxybutanoic acid is used for substitutions and chain elongations at the side‐chain C‐atom in the 6‐position of the heterocycle (→3–6, 10–13). Subsequent simultaneous reductive debromination and double‐bond hydrogenation (Pd/C,H2)occurs with essentially complete diastereoselectivity (>98% ds), with H transfer from the face opposite to the t‐Bu group (→15–20, Table 1). Hydrolytic cleavages of the dioxanones then lead to enantiomerically pure β‐hydroxy‐acid derivatives (overall self‐reproduction of the stereogenic center of 3‐hydroxybutanoic acid or alkylation in the 4‐position of this acid with preservation of configuration).
Synthese makrocyclischer Ketone durch Ringerweiterung; ein neuer Weg zu(±)‐Muscon
Authors: Bienz Stefan , Hesse Manfred 
Published: December 2004

Synthesis of Macrocyclic Ketones by Ring‐Enlargement Reactions; a New Path to (±)‐MusconeA new synthetic route to macrocyclic ketones is described. Starting from 2‐nitrocycloalkanones, the ring‐enlarged compounds of the type 4 and 5 were prepared in three steps. Reduction of the NO2 group with Bu3SnH and azobisisobutyronitrile led in moderate yields to simple β‐keto‐esters which were quantitatively hydrolyzed and decarboxylated to the ketones of the type 8 and 9. The interesting fragrances Exaltone® (8a) and (±)‐muscone (9a) were prepared in this way in overall yields of 22 and 18%, respectively.
Kombinierte Anwendung von NOE‐Experiment und Molekül‐Mechanik‐Rechnungen zur Lösung eines stereochemischen Problems
Authors: Bigler Peter , Tintelnot Marina 
Published: December 2004

Combined Application of NOE Experiment and Force‐Field Calculations for the Solution of a Stereochemical ProblemThe determination of NO effects using modern NMR techniques yields valuable information on internuclear distances in molecules. The correct interpretation of these effects in highly flexible molecules with anisotropic internal motions can be improved in reliability and efficiency by the concomitant application of force field calculation. The evaluation of an additional parameter from the results of such a calculation, which can directly be correlated with the experimental data, is demonstrated. Nevertheless, inherent problems in both the NOE measurements and molecular mechanics should be taken into account for a careful interpretation of the results.
Agnatasterone A and B, Unusual Pregnane Steroids Isolated from the North‐East Atlantic Sponge Axinella agnata
Authors: Guella Graziano , Pietra Francesco 
Published: December 2004

AbstractTwo novel pregnatrienolones isolated in very small amounts from the North‐East‐Atlantic demosponge Axinella agnata (Tetractinomorpha, Axinellida) are unique in having C(2)C(3) (or C(3)C(4)), C(7)C(8), and C(16)C(17) bonds and a 12β‐OH group which, being strongly H‐bonded to a 20‐keto group, resists acylation. 1H‐ and 13C‐NMR spectroscopy of the steroids and of products of their selective epoxidation or reduction allow us to propose the structures (+)‐12β‐hydroxy‐5α‐pregna‐2,7,16‐trien‐20‐one ( = agnatasterone A, (+)‐1), and (+)‐12β‐hydroxy‐5α‐pregna‐3,7,16‐trien‐20‐one ( = agnatasterone B. (+)‐5), for the two steroids with minimal recourse to model compounds.
Synthesis of Aristotelia‐Type Alkaloids. Part III. (3R,4R)‐ and (3R,4S)‐1‐p‐menthene‐3,8‐diol and the corresponding racemates: Preparation and assignment of configuration
Authors: Burkard Stefan , Looser Martin , Borschberg Hans‐Jürg 
Published: December 2004

AbstractA 1:1 mixture of the racemic trans‐ and cis‐1‐p‐menthene‐3,8‐diols ((±)‐3 and (±)‐4, resp.) was readily prepared in 3 steps starting from 3‐methyl‐2‐cyclohexen‐1‐one. The relative configuration of the diols, purified via the corresponding cyclocarbonates, was assigned by 1H‐NMR spectroscopy and found to be at variance with tentative claims in the literature. Optically active samples of 3 and 4 were prepared by resolution of the racemates with (R)‐1‐phenylethylamine. The absolute configuration of the resulting diols was determined by chemical correlation with standards of known absolute configuration.
Low‐Temperature X‐ray Crystal‐Structure Analysis of the Thermally Unstable Lithiated 2‐Butenyl tert‐Butyl Sulfide: A comparison with model ab initio MO calculations
Authors: Seebach Dieter , Maetzke Thomas , Haynes Richard K. , Paddon‐Row Michael N. , Wong Stephen S. 
Published: December 2004

AbstractSingle crystals of the N,N,N′,N′‐tetramethylethylenediamine (TMEDA) complex 6 of the title compound have been isolated. Compound 6 decomposes in the crystalline state above −20°. From the bond lengths and angles obtained by X‐ray crystal‐structure analysis (data collected at −70°), compound 6 is best described as a (E)‐1‐(tert‐butylthio)‐1‐lithio‐2‐butene with the double bond acting as an additional ligand on lithium (unsymmetrical allylic group). The S‐atom is in a cisoid arrangement in a common plane with the four C‐atoms of the butenyl system. The t‐Bu group and the Li‐atom are located above and below this plane. The structure is discussed with respect to the reactivity of 6 (α/γ reactivity). The gross structure is reproduced surprisingly well by an ab initio SCF MO calculation of the model lithiopropene‐1‐thiol 7(HS instead of t‐BuS, CH2 instead of CHCH3, no solvation of Li). The prominent difference is the symmetry of the allyllic moiety in the calculated structure.
Optically Pure Isoproterenol Analogues With Side Chains Containing an Amide Bond: Synthesis and biological properties
Authors: Märki Hans P. , Crameri Yvo , Eigenmann Rainer , Krasso Anna , Ramuz Henri , Bernauer Karl , Goodman Murray , Melmon Kenneth L. 
Published: December 2004

AbstractThe isoproterenol analogues 4a and 4b, synthesized as mixtures of Diastereoisomers, were shown to possess very potent β‐adrenoceptor agonistic activity. Therefore, the four possible diastereoisomers of 4a have been synthesized and tested for inotropic activity. The (6R, 2′R)‐diastereoisomer turned out to be the most interesting one. Consequently, also (6R,2′R)‐4b has been prepared and tested. For the diastereoselective synthesis, three variants have been elaborated: (i) coupling of epoxides 12 with amines 27 (Scheme 6); (ii) coupling of the activated glycol 17 with the amine 22 (Scheme 8); (iii) diastereoselective hydrogenation of the amino ketone 31 (Scheme 7). Both (6R,2′R)‐4a and (6R,2′R)‐4b show long lasting positive inotropic activity after intravenous as well as oral administration and are at least three times as potent as rac‐isoproterenol. In the anesthetized dog, a good separation of positive inotropic and positive chronotropic effects is observed. In conscious dogs, however, heart rate and contractile force increase to the same extent (possibly due to reflex tachycardia).
Light‐Induced Synthesis of Tricyclic Thiolane Derivatives from 2(5H)‐thiophenones via consecutive radical ring closure
Authors: Kiesewetter René , Graff Alan , Margaretha Paul 
Published: December 2004

AbstractTwo α,β‐unsaturated thiolactones, 5‐(2‐propynyl)‐2(5H)‐thiophenone (5) and 3,5‐di(2‐propenyl)−2(5H)‐thiophenone (6), were newly synthesized. Irradiation (λ = 300 nm) of 5 in MeOH containing cyclopentene afforded a 3:1 mixture of diasteroisomeric methyl 7‐thiatricyclo[6.4.0.02,6]dodec‐10‐ene‐12‐carboxylates (8a/8b), while irradiation of 6 in MeOH saturated with 2‐methylpropene gives a 3:2 mixture of diastereoisomeric methyl 3,3,9‐trimethyl‐5‐thiatricyclo[6.2.1.02,6]undecane‐1‐carboxylates (10a/10b).
1H‐and 13C‐NMR study of the dilithium naphthalene and its TMEDA complex
Authors: Benken Rainer , Günther Harald 
Published: December 2004

AbstractDilithium naphthalene (2) and its TMEDA complex 3 have been prepared, and their 1H‐and 13C‐NMR spectra were analyzed in terms of chemical shifts and coupling constants. From its Q value, 2 is characterized as delcoalized [4n] π system and the 1H ‐ as well as the 6Li‐NMR shifts classify the ion as strongly paratropic. For the quarternary C‐atoms, a down‐field shift of 30.4 ppm is observed. The conclusions drawn from the NMR parameters are compared with the results of MNDO calculations for naphthalene and biphenylene and their ions.
The Construction of New Proteins. Part III. Artificial folding units by assembly of amphiphilic secondary structures on a template
Authors: Mutter Manfred , Altmann Eva , Altmann Karl‐Heinz , Hersperger René , Koziej Pjotr , Nebel Kurt , Tuchsecherer Gabriele , Vuilleumier Stéphane , Gremlich Hans‐Ulrich , Müller Klaus 
Published: December 2004

AbstractA new general strategy for the construction of artificial proteins with predetermined tertiary structure is presented. Amphiphilic α‐helix and β‐sheet‐forming oligopeptides are assembled on a multifunctional ttemplate molecule which directs the peptide blocks to adopt characteristic folding topologies. The design, synthesis, and conformational properties of these template‐assembled synthetic proteins (TASP) are exemplified for βαβ‐, α‐helix‐bundle‐ and β‐barrel‐like tertiary structures using specially designed oligopeptides as template molecules. In contrast to linear polypeptide chains of comparable molecular weights, these conceptually novel marcromolecules are readily accessible to chemical synthesis and exhibit excellent solubility in a number of solvents. Experimental evidence is provided for a template‐induced intramolecular folding to secondary and tertiary structures in aqueous solutions. This approach opens new prospects for the chemical construction of biomacromolecules with tailormade structural and functional properties.
The adamantane rearrangement of syn‐ and anti‐Tricyclo[4.2.1.1.12,5] decane. Part II. Rearrangements initiated by regioselective formation of carbocations at C(3) and C(9)
Authors: Brossi Marco , Ganter Camille 
Published: December 2004

AbstractThe endo‐ and exo‐alcohols 5–12 of syn‐(1) and anti‐tricyclo[4.2.1. 12.5]decane (2) were treated with BF3/Et3SiH (ionic hydrogenation) in order to study the behaviour of the corresponding regioselectively generated carbocations at C(3) (a (syn), b (anti)) and C(9) (c (syn), d (anti)). The anti‐hydrocarbon 2 is practically the sole product obtained starting with the four 3‐alcohols (via a→b from 5 and 6 (syn) and via b from 9 and 10 (anti)). The four 9‐alcohols in each case yield a mixture of 2‐endo, 3‐endo‐ (3) and 2‐exo,3‐exo‐trimethylene‐8,9,10‐trinorbornane (4) (via c → e from 7 and 8 (syn) and via d → f from 11 and 12 (anti)), but no hydrocarbon 2, i.e. none of the 1,3‐H shifts c → a and d → b is involved.
α‐Alkylierung von β‐Hydroxycarbonsäuren über 1,3‐Dioxan‐4‐on‐Enolate
Authors: Zimmermann Jürg , Seebach Dieter , Ha Tae‐Kyu 
Published: December 2004

Highly Diastereoselective α‐Alkylation of β‐Hydroxycarboxylic Acids Through Lithium Enolates of 1,3‐Dioxan‐4‐onesFrom serine, β‐hydroxyisobutyric acid (‘Roche’ acid) and β‐hydroxybutyric acid, the dioxanones 1–6 were prepared. The generation of the enolates of type I with LDA at −75° and alkylation gave products with trans‐configuration whereas protonation of the 5‐methyl‐substituted enolate allowed access to the cis‐configurated β‐hydroxybutyric‐acid derivative 12. Hydrolysis gave the free β‐hydroxy acids of ‘syn’‐and ‘anti’‐configuration. Alkylation of the 6‐unsubstituted dioxanones 1 and 3 yielded predominantly products resulting from attack in the cis‐position of the t‐Bu group. The ‘reactive’ conformation of the enolates involved is tentatively derived from the product configuration. The selectivity of the alkylation is also discussed in terms of the results of an ab‐initio calculation on the enolates M–P.
Stereoselectivity in Reactions of Metal Complexes. Part X. Kinetics and stereoselectivity of the inner‐sphere electron‐transfer reaction between [Co(bamap)H2O]+ (bamap = 2,6‐bis(3‐carboxy‐1,2‐dimethyl‐2‐azapropyl)pyridine) and optically active iron(II) complexes
Authors: Bernauer Klaus , Pousaz Philippe , Porret Joelle , Jeanguenat André 
Published: December 2004

AbstractThe kinetics of the electron‐transfer reaction between racemic or optically active [Co(bamap)H2O]+ and optically active Fe2+ complexes of the three new pentadentate ligands bamap, alamp, and valmp has been investigated. All the reacting species show C2 symmetry. With respect to aquo‐Fe2+, the reaction rate for the Fe2+ complexes is enhanced by a factor of 104 to 105, and the observed kΔΛ/kΛΛ ratio is 1.0, 1,9, and 1.2, respectively. In all cases where stereoselectivity is observed, the reaction is faster between the complexes of opposite absolute configuration (ΔΛ or ΛΔ) than between species with the same configuration (ΛΛ or ΔΔ). The stereoselectivity effects are discussed of the basis of the structure of the transition state and the interatomic distances between the two metal centers at the moment of electron transfer.
Synthesis of (+)‐1,3:2,5‐dianhydroviburnitol ((+)‐(1R,2R,3S,5R,6S)‐4,7‐dioxatricyclo[3.2.1.03,6]octan‐2‐ol)
Authors: Le Drian Claude , Vogel Pierre 
Published: December 2004

AbstractEpoxidation of (−)‐(1R,2R,4R)‐2‐endo‐cyano‐7‐oxabicyclo[2.2.1]hept‐5‐en‐2‐exo‐yl acetate ((−)‐5) followed by saponification afforded (+)‐(1R,4R,5R,6R)‐5,6‐exo‐epoxy‐7‐oxabicyclo[2.2.1]heptan‐2‐one ((+)‐7). Reduction of (+)‐7 with diisobutylaluminium hydride (DIBAH) gave (+)‐1,3:2,5‐dianhydroviburnitol ( = (+)‐(1R,2R,3S,4R,6S)‐4,7‐dioxatricyclo[3.2.1.03,6]octan‐2‐ol; (+)‐3). Hydride reductions of (±)‐7 were less exo‐face selective than reductions of bicyclo[2.2.1]heptan‐2‐one and its derivatives with NaBH4, AlH3, and LiAlH4 probably because of smaller steric hindrance to endo‐face hydride attack when C(5) and C(6) of the bicyclo‐[2.2.1]heptan‐2‐one are part of an exo oxirane ring.
Generic shapes for the conformation analysis of macrocyclic structures
Authors: Gerber Paul R. , Gubernator Klaus , Müller Klaus 
Published: December 2004

AbstractA new algorithm for the systematic generation of conformations of macrocyclic systems is presented. The procedure is based on the concept of generic shapes that are found in such structures. These shapes are characterized by a selection of harmonics which occur in an approximate Fourier representation of the atomic coordinates of the rings. Following a fixed protocol, a limited set of in‐plane and out‐of‐plane circular harmonics is used to define an ensemble of generic ring shapes. These generic shapes are used as start structures for energy minimizations by a given force‐field method. To account for the possibility of having several final conformations originating from the same generic shape, the corresponding initial structure is taken several times and subjected to a randomization step before minimization. The resulting conformations that fall within a preset low‐energy band are collected and screened for duplicates and enantiomers. The efficiency of this procedure (ratio between the number of accepted conformations and the total number of energy minimizations) depends on the flexibility of the macrocyclic system. The efficiency is generally quite high for very flexible rings. According to the proposed protocol, the number of generic shapes used as start structures grows as the square of N(lnN), where N is the ring size. The algorithm lends itself to conformational analyses of medium‐size and large rings as well as of loops spanned between fixed structural units.