bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of enantiomerically pure indoloquinolizine derivatives
Authors: Shiqi Peng , Li Zhang , Mengshen Cai , Winterfeldt Ekkehard
Published: July 2007

L‐Tryptophan methyl ester reacts with 1,1,3,3‐tetramethoxypropane to give methyl carbolinecarboxylate 2 as a 1:2 mixture of the (1R,3S) and (1S,3S) stereoisomers. Conversion to the corresponding amides (1R,3S)‐3 and (1S,3S)‐3 was accomplished by treatment of 2 with ammonia. Benzylation of (1R,3S)‐3 or (1S,3S)‐3 afforded the corresponding 2‐benzylcarbolineamide (1R,3S)‐4 or (1S,3S)‐4. Dehydration of the amide group in (1R,3S)‐4 or (1S,3S)‐4 yielded the corresponding 2‐benzylcarbolinenitrile (1R,3S)‐5 or (1S,3S)‐5, which was treated with NaBH4 to reductively remove the cyano group. Hydrogenation removed the benzyl‐protectin group of 6 resulting in (1R)‐7 or (1S)‐7, which is then alkylated with methyl vinyl ketone to give the Michael adduct (1R)‐8 or (1S)‐8. Subsequent Aldol reaction and dehydration afforded the enantiomerically pure indoloquinolizine derivatives (12bR)‐9 or (12bS)‐9, which was shown to be enantiomerically pure by recording their 1H‐NMR spectra in the presence of a chiral shift reagent.
Synthese von Manzamin C, Infractin und 6‐Hydroxyinfractin
Authors: Nowak Wolfgang , Gerlach Hans
Published: July 2007

Synthesis of Manzamine C, Infractine and 6‐Hydroxyinfractine

Manzamine C (1), a β‐carboline alkaloid with antitumor activity isolated from the marine sponge Haliclona sp. was synthesized. The dilithium derivative of 5‐hexynoic acid (6) was alkylated with 7 to give after esterification the methyl 10‐hydroxy‐5‐decynoate (8). The tosylate of 8 was converted into the azide 9 which could be selectively hydrogenated with Lindlar palladium catalyst to give the amino ester 10. Saponification of 10 and acylation with (Boc)2O yielded 11, which was converted with pentafluorophenol into 12. Removal of the Boc group in 12 gave an amino ester as intermediate, which cyclized immediately under high dilution conditions to give the lactam 13 in high yield. Reduction of 13 with LiAlH4 produced the macrocyclic amine 4. The β‐carboline part of 1 was prepared by condensation of N‐benzyltryptamine 14 with the formylacetic acid equivalent 15 to give 16. Dehydrogenation of 16 with Pd‐on‐carbon catalyst led to the orthoester 17, which could be converted into the methyl ester 5 in high overall yield. The 4‐(dimethylamino)pyridine‐catalyzed substitution of the methyl ester function in 5 by the amine 4 gave the amide 29. The analogous reaction of 5 with pyrrolidine or with azacyclotridecane yielded 30 and 31. Reduction of these three amides with LiAlH4 produced 1, 2 and 3. The spectroscopic properties of 1 were identical with those of natural manzamine C. – Condensation of 14 or N‐benzyl‐5‐(benzyloxy)tryptamine (19) with aldehyde 18 yielded the products 20 and 21, which could be dehydrogenated to furnish 22 and 23. From these the methyl esters 24 and 25 with properties identical to those of the known β‐carboline alkaloids infractine and 6‐hydroxyinfractine could be obtained.
Free‐radical Cyclization of Petroselinic Acid
Authors: Metzger Jürgen O. , Mahler Ralf
Published: July 2007

Petroselinic acid was cyclized via methyl 2‐iodopetroselinate (1) with tributyltin hydride to give methyl trans‐ and cis‐2‐dodecyl‐1‐cyclopentanecarboxylate (2). The atom‐transfer method with hexabutylditin resulted in the formation of bicyclic γ‐lactones 4 and methyl trans‐2‐(1′‐iodododecyl)‐1‐cyclopentanecarboxylate (trans‐5). The same products were obtained with the new initiator system SnCl2/AgOAc. This method showed, if compared with the other methods, the shortest reaction time, the highest yield and stereoselectivity combined with a very simple workup procedure and the use of less toxic chemicals.
Syntheses and Cardiovascular Activity of Stereoisomers and Derivatives of Eburnane Alkaloids
Authors: Czibula László , Nemes András , Visky György , Farkas Mária , Szombathelyi Zsolt , Kárpáti Egon , Sohár Pál , Kessel Martin , Kreidl János
Published: July 2007

The synthesis of all the possible isomers of the eburnameninevincamine type alkaloids 1b, 2a, 3a and derivatives 4, 8, 9, 10 is described. Structures were determined by 1H‐ and 13C‐NMR spectroscopy including special techniques such as DR, DEPT, DNOE, and 2D‐HSC. In contrast to the known cerebrovascular effects of cis‐(3S,16S) compounds, trans‐(3S,16R) derivatives show a significant peripheral vasodilator effect.
Herkunft des Kohlenstoff‐Grundskeletts von F‐Säuren
Authors: Scheinkönig Josef , Spiteller Gerhard
Published: July 2007

Origin of the Basic Carbon Chain of F Acids

Feeding experiments with sodium [2‐13C]acetate on suspension cultures of Saccharum spec. show that the basic carbon chain of F acids 1 is derived from acetate units via the fatty acid pathway. Incorporation of 13C label was confirmed by GC/MS analysis of the corresponding tetrahydrofuran derivatives 2.
Unexpected Formation of 3,6‐Anhydrofuranoses by Acid Treatment of Methyl 2,3‐Di‐O‐acyl‐D‐glycopyranosides
Authors: Ziegler Thomas , Vollmer Martin , Oberhoffner Sven , Eckhardt Elisabeth
Published: July 2007

Treatment of methyl 2,3‐di‐O‐acyl‐D‐glycopyranosides 1 of glucose and mannose with catalytic amounts of trifluoromethanesulfonic acid afforded the corresponding bis(5‐O‐acyl‐3,6‐anhydro‐D‐glycofuranose) 1,2′:2,1′‐dianhydrides 6 in 12–58% yield the structure of which was confirmed for the α‐D‐glucose derivative 6a by an X‐ray analysis. In addition, in the presence of methyl pyruvate (2a) or methyl 2‐acetoxy‐acrylate (2b) various amounts of diastereomeric 3,6‐anhydro‐5‐O‐benzoyl‐1,2‐O‐(1‐methoxycarbonyl)ethylidene‐α‐D‐glucofuranoses 5 and acylated methyl α‐D‐glucopyranosides 3 and 4, respectively, were formed.
Darstellung von (3‐Amino‐1‐alkenyl)phosphonsäuren aus allylischen α‐ und γ‐Hydroxyphosphonaten. Sigmatrope Umlagerung von (1‐Azido‐2‐alkenyl)phosphonsäureestern
Authors: Öhler Elisabeth , Kotzinger Silvia
Published: July 2007

Synthesis of (3‐Amino‐1‐alkenyl)phosphonic Acids from Allylic α‐ and γ‐Hydroxyphosphonates. – Sigmatropic Rearrangement of Dialkyl (1‐Azido‐2‐alkenyl)phosphonates

(3‐Azido‐1‐alkenyl)phosphonates 8 with R1 = H are prepared regioselectively by reaction of secondary (1‐hydroxy‐2‐alkenyl)phosphonates 3 with TPP/DEAD/HN3 and subsequent thermal 1,3‐rearrangement of the allylic α‐azidophosphonates 5 primarily formed. (3‐Azido‐1‐alkenyl)phosphonates 8 with R1 ≠ H are conveniently obtained from the regioisomeric tertiary 3‐hydroxy derivatives 4, which can be prepared either by allylic rearrangement of the corresponding α‐hydroxyphosphonates 3, or by NaBH4 reduction of the (3‐oxo‐1‐alkenyl) derivatives 7. The synthetic utility of the azido compounds 8 is demonstrated by their conversion into the (3‐amino‐1‐alkenyl)phosphonic acids 11 and the N,O‐protected derivatives 12 and 13, and to the saturated γ‐aminophosphonates 14.
Alkaloide aus Veratrum patulum, I. Isolierung und Strukturaufklärung neuer Steroidalkaloidglycoside
Authors: Irsch Eva‐Maria , Pachaly Peter , Breitmaier Eberhard , Sin Kwan‐Seog
Published: July 2007

Alkaloids from Veratrum patulum, I. – Isolation and Structure Elucidation of New Steroid Alkaloid Glycosides

Herrn Professor Dr. F. Zymalkowski zum 80. Geburtstag gewidmet.

Beside the known veratrosine (1), two new steroid alkaloid glucosides, 23‐O‐β‐D‐glucopyranosyl‐20‐isoveratramine (2) and (22S,23R,25S)‐23‐O‐β‐D‐glucopyranosyl‐5,11,13‐veratratrienine‐3β,23‐diol (3), were isolated from the roots of Veratrum patulum Loes. fil. (Liliaceae) and characterized by spectroscopic methods.
Reaktionen von Benzothiet mit Iminen
Authors: Meier Herbert , Saul Klaus , Jacob Dominic
Published: July 2007

Reactions of Benzothiete with Imines

A great variety of compounds 3a–w containing CN double bonds was studied in the reaction with benzothiete (1). H, alkyl, aryl, OR, SR and NR groups can be attached to the imino function. The azomethines 3a–f, the thiazolines 3g–i, the lactim 3n, the oximes 3r–t, the isoxazolinone 3u and the azine 3v show [8π + 2π] cycloaddition reactions yielding derivatives of 1,3‐benzothiazine (4a–i, n, r–v). In the case of 4n, s, t secondary reactions occur, initiated by elimination processes. [8π + 2π] Cycloadditions account also for the reactions 3e → 10, 11, 3o → 18(I), and 3q → 19; however, CC double bonds are representing the 2π component in these examples. The thiazoline 3j and the oxazolines 3k–m afford dibenzo‐1,8,4‐thiazaundecine derivatives 14j–m, in which two benzothiete units are incorporated. The hydrazone 3w gives the linear adduct 22. Compounds with a heteroaromatic tautomeric form like 3p don't react at all. The reactions of 1 and 3 are very sensitive towards electronic and steric effects and have always to compete with the dimerisation 1 → 5. Thus, the product yields vary between 90 and 2%.
Asymmetric Synthesis via Heterocyclic intermediates, L. – Trichloroacetimidates, II. Asymmetric Synthesis of α‐Amino Acid Benzyl Esters via the Bisbenzyl Bislactim Ether of cyclo(‐L‐Val‐Gly‐)
Authors: Groth Ulrich , Schmeck Carsten , Schöllkopf Ulrich
Published: July 2007

The diketopiperazine cyclo(‐L‐Val‐Gly‐) (1) can be O‐alkylated under mild acidic reaction conditions with the alkyl trichloroacetimidates 2 to the corresponding bisalkyl bislactim ethers. Alkylation of the bisbenzyl bislactim ether anion of cyclo(‐L‐Val‐Gly‐) 4c with benzyl bromide and subsequent hydrolysis with aqueous trifluoroacetic acid afforded D‐phenylalanine benzyl ester (8) with an enantiomeric excess of > 95%.
Studies on the Constituents of the Leaves of Tinospora tuberculata, I. – Isolation and Structure Elucidation of two New Furanoid Diterpenes, Tinotufolin A and B
Authors: Fukuda Naomichi , Nakamura Motoyuki , Yonemitsu Michiko , Kimura Takeatsu , Isobe Ryuichi , Komori Tetsuya
Published: July 2007

Two new furanoid diterpenes, tinotufolin A (1) and B (2) were isolated from the fresh leaves of Tinospora tuberculata Beumée (Menispermaceae). The structures of 1 and 2 were elucidated on the basis of chemical and spectroscopic findings.
Photochemische Reaktion von Aminophenazon mit Ephedrin
Authors: Wolff Joachim H. , Wolff J. Jens , Nuber Bernhard
Published: July 2007

Photochemical Reaction of Aminophenazone with Ephedrine

Herrn Dr. Wolfgang Seiffert aus Anlaß seiner Pensionierung gewidmet.

The structure of 3, a reaction product of aminophenazone 1 and ephedrine 2 under UV irradiation in the presence of water, is elucidated by X‐ray structure analysis. The proposed mechanism of its formation features the aziridinone 4 as a key intermediate.
The Structure of Verbascosaponin
Authors: Schöderh Harald , Haslinger Ernst
Published: July 2007

The structure of verbascosaponin was revised. Using 2D‐NMR techniques (COSY, TOCSY, NOESY, ROESY, HMQC, DEPT‐COSY, HMQC‐TOCSY and HMBC) and selective excitation, we established the structure of 1 as 3β‐O‐{α‐L‐rhamnopyranosyl‐(1→4)‐β‐D‐glucopyranosyl‐(1→3)‐[β‐D‐glucopyranosyl‐(1→2)‐]‐β‐D‐fucopyranosyl}‐13β,28‐epoxyolea‐11‐en‐23α‐ol. A second saponin 2 was isolated from the officinal drug Flores Verbasci and its structure determined as 11‐methoxy‐3β‐O‐{α‐L‐rhamnopyranosyl‐(1→4)‐β‐D‐glucopyranosyl‐(1→3)‐[β‐D‐glucopyranosyl‐(1→2)‐β‐D‐fucopyranosyl]olea‐12‐en‐23α,28β‐diol.
A Practical Syntheis of the Khapra Beetle Pheromones
Authors: Pawar Archana S. , Chattopadhyay Subrata , Mamdapur Vasant R.
Published: July 2007

A practical synthesis of the title pheromones is described. The features of the synthesis include high optical purities of the target compounds, utilization of easily accessible materials and employment of operationally simple and facile reactions.
A Simple Procedure for the Synthesis of Carbohydrate Ortholactones
Authors: Žagar Cyrill , Scharf Hans‐Dieter
Published: July 2007

3,4‐Di‐O‐benzyl‐2,6‐dideoxy‐L‐arabino‐hexono‐1,5‐lactone (1b) was synthesized in three steps by starting from di‐O‐acetyl‐L‐rhamnal (6). Sequential treatment of 1b or 3,4,6‐tri‐O‐benzyl‐2‐deoxy‐D‐arabino‐hexono‐1,5‐lactone (1a) with triethyloxonium tetrafluoroborate and sodium ethanolate produced the diethyl ortholactones 2a and b. Acid‐catalyzed reaction of 2a or b with 1,2‐ethanediol (5a) or (1S,2S)‐1,2‐cyclohexanediol (5b) gave the spiro ortholactones 3a, b, and 4a, b.
Synthesis of Substituted Indoles and Pyrimido[4,5‐b]indoles by Dehydrogenation of Tetrahydroindoles and Tetrahydropyrimidoindoles
Authors: Eger Kurt , Lanzner Wolfgang , Rothenhäusler Klaus
Published: July 2007

The synthesis of N1‐substituted 2‐amino‐4,5,6,7‐tetrahydroindole‐3‐carbonitriles 2 and 5,6,7,8‐tetrahydropyrimido[4,5‐b]‐indoles 3–5 and their subsequent dehydrogenation to the corresponding 2‐aminoindole‐3‐carbonitriles 8 and pyrimido[4,5‐b]indoles 9, 11, 12, using DDQ in toluene or palladium on charcoal in 1‐methylnaphthalene, is described. Palladium on charcoal proves to be a versatile reagent in dehydrogenation. The application of DDQ fails in the case of the 5,6,7,8‐tetrahydropyrimido[4,5‐b]indole‐4‐amines 4, 5, which are of special interest in regard of their affinity to the adenosine receptor. With sodium periodate, instead of the expected aromatization a new class of spiro‐heterocycles is formed.
Asymmetrische Synthesen mit chiralen 1,4‐Oxazin‐2,5‐dionen: Darstellung enantiomerenreiner 2‐substituierter Pipecolinsäurederivate
Authors: Wanner Klaus Th. , Stamenitis Stamatios
Published: July 2007

Asymmetric Synthesis with Chiral 1,4‐Oxazine‐2,5‐diones: Preparation of Enantiomerically Pure 2‐Substituted Pipecolic Acid Derivatives

Herrn Prof. Dr. H.‐D. Stachel mit den besten Wünschen zum 65. Geburtstag gewidmet.

A new asymmetric synthesis of α‐amino acids is presented. This synthesis is based on the chiral 1,4‐oxazine‐2,5‐diones 5 and 14 relying on the α‐hydroxy acid 12 as a chiral auxiliary. A base‐mediated alkylation of these chiral amino acid building blocks (5, 12) with different alkyl halides proceeds, after deprotonation with sec‐butyllithium, with high yields and excellent d.s. (up to 99.5/0.5). As exemplified by the synthesis of 15 (in comparison to that of 7a) the absolute configuration of the stereocenter in the amino acid unit is determined by the sequence the substituents are introduced. In the enolate 6 and in that of 14 the electrophile adds consistently to the re face of the prochiral carbon. From the alkylation products the corresponding 2‐substituted pipecolic acid derivatives are obtained in good yields upon hydrolysis under basic or acidic conditions.
“Head‐to‐Tail” Cyclization of Hexapeptides Using Different Coupling Reagents
Authors: Zimmer Susanne , Hoffmann Eike , Jung Günther , Kessler Horst
Published: July 2007

In the synthesis of cyclic hexapeptides the cyclization step was examined by using different procedures for activation. Three coupling methods were tested for “head‐to‐tail” cyclization of the resin‐cleaved peptides in solution: (1) DPPA/NaHCO3; (2) TBTU/HOBt/DIEA and (3) HBTU/HOBt/DIEA. The best results were obtained by using TBTU. Reaction rates were 5 to 70 times faster with the TBTU procedure compared to the DPPA activation and generally complete conversions to cyclopeptides were observed. The kinetics of the cyclizations under high dilution conditions were monitored by HPLC. During the synthesis of the linear peptides the formation of an aminosuccinimide was observed. This by‐product was characterized by electrospray MS and NMR.
Tetrahydrofurane und γ‐Lactone, VI. Optisch aktive N‐Boc‐δ‐Amino‐γ‐lactone aus Cyclooctin und Furan
Authors: Meints Martin , Wolff Christian , Tochtermann Werner
Published: July 2007

Tetrahydrofurans and γ‐Lactones, VI. – Optically Active N‐Boc‐δ‐Amino‐γ‐lactones from Cyclooctyne and Furan

The stereoselective synthesis of the title compounds (−)‐(2′R,8S)‐2b and (+)‐(2′S,8R)‐2b from (2′R,8R)1a and (2′S,8S)‐1a is described. The unprotected amino lactone 2c undergoes rearrangement to the γ‐hydroxy‐δ‐lactam 3a by treatment with hydrogen chloride.
The Biosynthesis of the Cularine Alkaloids
Authors: Mueller Martin J. , Zenk Meinhart H.
Published: July 2007

In order to study the cularine biosynthesis, L‐[β‐13C]tyrosine (L‐18), [α‐13C]tyramine (20), L‐[3′‐18O]DOPA (L‐19) and [α‐13C, 3′‐18O]dopamine (21) were synthesized and fed to Corydalis claviculata and Sarcocapnos crassifolia plants, which are rich sources of cularine‐type alkaloids. (S)‐Crassifoline [(S)‐15, an established cularine (1) precursor] and cularine‐type alkaloids subsequently isolated, showed upon L‐[β‐13C]tyrosine feeding approximately equal labeling (1:0.8) of the isoquinoline and benzyl moiety, whereas the other precursors were solely incorporated into the isoquinoline half, indicating that three of the four oxygen functions present in cularine‐type alkaloids are derived from simple, early precursors. The fourth oxygen atom appears to be introduced later into a trioxygenated alkaloidal intermediate. [α‐13C, 3‐18O]Dopamine was incorporated into the upper half of the 7,8‐oxygenated (S)‐crassifoline [(S)‐15] molecule, without loss of 18O‐label. This fact excludes an isomerization mechanism of 6,7‐oxygenated isoquinolines through a dehydroxylation/hydroxylation step. Furthermore, these findings proved to be correct by separate feeding experiments with a novel 3′,7,8‐trihydroxylated (S)‐tetrahydrobenzylisoquinoline [(S)‐10] and its 3′,6,7‐trihydroxylated isomer, (S)‐norcoclaurine [(S)‐9], the common precursor of benzylisoquinoline alkaloids in nature. The first alkaloid was exclusively biotransformed into (S)‐crassifoline [(S)‐15] and cularine‐type alkaloids, whereas (S)‐norcoclaurine [(S)‐9] was only metabolized to its well established metabolite, (S)‐reticuline [(S)‐16], but not to cularine‐type alkaloids. Feeding experiments with (S)‐ and (R)‐[1‐13C]norjuziphine [(S)‐11, (R)‐11], (RS)‐[N‐13C]juziphine [(RS)‐13], (RS)‐[N‐13C]3′‐hydroxyjuziphine [(RS)‐14] and (RS)‐[N‐13C]crassifoline [(RS)‐15] confirmed a new pathway to (S)‐crassifoline and the (S)‐configurated cularine‐type alkaloids 1–5, and showed in addition that there must be at least one enzyme in the pathway which is (S)‐stereospecific.
Zur Konformation und Konfiguration der Cholecalciferol‐Isoxazolin‐Addukte
Authors: Reischl Wolfgang , Hofer Otmar , Weissensteiner Walter
Published: July 2007

On the Conformation and Configuration of the Cholecalciferol‐Isoxazoline Adducts

The conformation and configuration of compounds 1–4, generated by 1,3‐dipolar addition of nitrile oxides to the exomethylene group of (5Z)‐ and (5E)‐vitamin D3 has been assigned. A combination of force‐field calculations, LIS measurements, LIS simulations and CD spectroscopy has been used. In addition, the assignment has been verified by chemical correlation of 1 and 3 to 5 as well as of 2 and 4 to 6.
Electroorganic Synthesis, 54. Enantioselective Cathodic Reduction of 4‐Substituted Coumarins with Alkaloids as Catalysts, 1
Authors: Schoo Norbert , Schäfer Hans‐J.
Published: July 2007

The optical yield in the alkaloid‐catalyzed enantioselective electroreduction of 4‐methylcoumarin (1a) was increased from 17% to 47.4% by systematic variation of the electrolysis conditions. The results are explained by an induction mechanism in which the adsorbed protonated alkaloid acts as a chiral proton donor towards a prochiral carbanion derived from 1a. The preferred configuration of the product and the results obtained by variation of the alkaloid structure allow us to propose a model of the transition state. Furthermore, 4‐phenylcoumarin (1b) and 4‐(trifluoromethyl)coumarin (1c) were reduced with 13.2% and 8.4% ee, respectively.
Enantioselective cathodic reduction of 4‐substituted coumarins with alkaloids as catalysts, 2. AM1 and force‐field study of the transition‐state model
Authors: Höweler Udo , Schoo Norbert , Schäfer Hans‐J.
Published: July 2007

The experimental data presented in Part 1 of this series lead to a refined model for the transition state of the alkaloid‐induced enantioselective electroreduction of 4‐methylcoumarin. This model is based on a zwitterionic complex formed by the protonated alkaloid and the reduced species of the coumarin. The complex is studied by a combination of quantum chemical and molecular mechanics methods. The reactant geometries and their charge distributions are determined by the semiempirical AM1 method. The MOBY force field is used for a complete conformational analysis and optimization of the complexes. In agreement with experiment, an optical induction is found for yohimbine while its isomer rauwolscine shows no stereoselectivity. An upper limit for the distance between the reactants in the zwitterionic complex is determined and criteria for improved inductors are developed.
A novel selective route to 1‐substituted benzotriazoles via lithiation of simple 1‐alkylbenzotriazoles
Authors: Katritzky Alan R. , Wu Jing , Kuzmierkiewicz Wojciech , Rachwal Stanislaw
Published: July 2007

1‐Methylbenzotriazole (2a) is lithiated readily with butyllithium or LDA at the methyl group to 4 and the subsequent reaction with various electrophiles provides 1‐substituted benzotriazoles 5. Other 1‐(n‐alkyl)benzotriazoles 2 also undergo lithiation with LDA, the carbanions can be trapped with alkyl halides giving benzotriazoles 6 bearing secondary alkyl groups on the N‐1 atom. On standing in the absence of electrophiles, all the lithium derivatives decompose to afford complex mixtures. magnified image
Unusual reactivity of lithiated 2‐alkylbenzotriazoles
Authors: Katritzky Alan R. , Wu Jing , Kuzmierkiewicz Wojciech , Rachwal Stanislaw , Balasubramanian Marudai , Steel Peter J.
Published: July 2007

Treatment of a 2‐alkylbenzotriazole (BtCH2R) (2) with LDA at −78°C produces rapidly a mixture of a coupling product (BtCHR–CHRBt) (5) and a compound formed from four molecules of the starting material (BtCHR–CHR–CHR–CHRBt) (6). A mixture of 2‐methylbenzotriazole and benzophenone, treated with LDA, gives adduct Ph2C(OH)CH2Bt (14) quantitatively whereas benzaldehyde does not react under these conditions. 2‐Alkylbenzotriazoles (2) are alkylated at the α‐carbon atom when their mixtures with alkyl halides are treated with LDA. magnified image
Neue Synthesen von Heterocyclen mit Vinyl‐ und Divinylcarbodiimiden: Pyrrole, Triazole, Pyrimidine, Pyrindine, Isochinoline und Thiazolyl‐isothiazole
Authors: Capuano Lilly , Hammerer Volker , Huch Volker
Published: July 2007

New Syntheses of Heterocycles with Vinyl‐ and Divinylcarbodiimides: Pyrroles, Triazoles, Pyrimidines, Pyrindines, Isoquinolines and Thiazolyl‐isothiazoles

The title compounds 3 and 4 react with diazomethane either by loss or by retention of the diazo nitrogen, to afford 3,4‐dihydro‐2‐imino‐2H‐pyrroles 6 and 10 or the vic‐triazole 5, respectively. The structure of 5 has been established by X‐ray diffraction analysis. – The [4 + 2] addition of benzylidene methylamine or alicyclic enamines 9 to 4 results in the formation of partially hydrogenated pyrimidine 7, pyrindine 11a or isoquinoline 11b. – Thermolysis of 4 proceeds with spontaneous dehydrogenation, giving high yields of 1‐(1‐in‐dolyl)isoquinolines 8. – The derivative 10a, when melted with sulfur, undergoes both dehydrogenation and sulfur insertion, whereby the hitherto unknown thiazolyl‐isothiazole 13 is formed. Its structure has been elucidated by an X‐ray diffraction analysis. – A synthesis of the imidazo[2,1‐a]isoquinoline derivative 16 is reported. magnified image
Synthese von (+)‐Coriolin B aus (+)‐Präcoriolin
Authors: Weinges Klaus , Braun Ralf
Published: July 2007

Synthesis of (+)‐Coriolin B from (+)‐Precoriolin

Enantiomerically pure (3aS,3bR,4R,6aS,7S)‐(+)‐3,3a,4,5,6,6a,7‐Octahydro‐4,7‐dihydroxy‐3a,5,5‐trimethyl‐3‐methylene 2H‐cyclopenta[a]pentalen‐2‐one [(+)‐precoriolin] (4), produced from (S)‐(+)‐carvone (3), is converted via the epoxides 5 and 7 into (+)‐coriolin B (2). magnified image
Pseudosugars, 33. Synthesis of some 5a‐carbaglycosylamides, glycolipid analogs of biological interests
Authors: Tsunoda Hidetoshi , Ogawa Seiichiro
Published: July 2007

Five carbocyclic analogs of glycosylamides, N‐(5a‐carba‐D‐glycopyranosyl)‐N‐octadecyldodecanamides 2–6, having β‐galacto, α‐ and β‐gluco‐, and α‐ and β‐manno configurations, were synthesized by coupling of the protected anhydro derivatives 12, 15, and 21 of 5a‐carba‐sugars with octadecylamine, followed by N‐acylation. Walden inversion of the 2‐OH functions of 17 and 24 was carried out through O‐sulfonylation. A bioassay (in vivo) of 5a‐carbaglycosylamides showed that they are potent immunomodulators, obviously comparable to the true sugar analogs, suggesting that the 5acarbasugar analogs may provide appropriate model compounds for biochemical studies in glycolipid chemistry. magnified image
Pheromone, 95. Darstellung und Einsatz deuteriummarkierter Lepidopterenpheromone und Analoger zum Studium der Pheromonbiosynthese
Authors: Bestmann Hans Jürgen , Fett Dieter , Garbe Wolfgang , Gunawardena Neelakanta , Martichonok Valerij , Vostrowsky Otto
Published: July 2007

Pheromones, 95. – Synthesis and Application of Deuterium‐Labelled Lepidoptera Pheromones and Analogues for the Study of Pheromone Biosynthesis

By deuteration of suitable alkynes with D2 and Wilkinson catalyst deuterium‐labelled building blocks are obtained which can be transformed into the corresponding [D4]‐, [D8]‐ and [D9]‐labelled pheromones and pheromone analogues. These unsaturated deuterium‐marked compounds can be converted into saturated [D6]‐ and [D8]‐analogues of Lepidoptera pheromones by a second deuteration or subsequent hydrogenation. The analogues, comprising potential biosynthesis precursors of pheromones, were applied in vivo to female insects and deuterium incorporation into the final products of biosynthesis was recorded by GCMS. magnified image
Synthese von fungicid wirksamen (1H‐1,2,4‐Triazol‐1‐yl‐methyl)silanen und ‐siloxanen
Authors: Liebner Falk , Bankwitz Uwe , Rühlmann Klaus
Published: July 2007

Synthesis of Fungicidal (1H‐1,2,4‐Triazol‐1‐yl‐methyl)silanes and ‐siloxanes

The synthesis of FlusilazoleTM (1a) was substantially improved by thorough exclusion of oxygen nucleophiles in the reaction of (chloromethyl)bis(4‐fluorophenyl)methylsilane with sodium 1H‐1,2,4‐triazolide. New α,α‐diaryl‐α‐(1H‐1,2,4‐triazol‐1‐yl‐methyl)siloxanes 3 were obtained firstly from diaryl(1H‐1,2,4‐triazol‐1‐yl‐methyl)silanols or ‐silanolates, which were prepared by different methods from the corresponding silanol hydrochlorides and further treated with functional, linear oligodimethylsiloxanes or secondly from α,α‐diaryl‐α‐(chloromethyl)siloxanes and 1‐(trimethylsilyl)‐1H‐1,2,4‐triazole. The siloxane 4 containing a triazolylmethyl group and additionally silicofunctional coupling groups could be synthesized by hydrosilylation of an α‐triazolylmethyl‐ω‐vinylsiloxane with triethoxysilane. magnified image
Ringtransformationen von 1‐Oxa‐5,6‐diazaspiro[2.4]hept‐6‐en‐4‐onen zu 4,5‐Dihydro‐4‐hydroxy‐1H‐pyrazol‐4‐carbonsäure‐Derivaten
Authors: Kirschke Klaus , Hübner Petra , Lutze Gerhard , Gründemann Egon , Ramm Matthias
Published: July 2007

Ring Transformations of 1‐Oxa‐5,6‐diazaspiro[2.4]hept‐6‐en‐4‐ones into 4,5‐Dihydro‐4‐hydroxy‐1H‐pyrazole‐4‐carboxylic Acid Derivatives

Spiro epoxides 3 were synthesized from 1H‐pyrazol‐5(4H)‐ones 1 by Knoevenagel condensation with acetone or benzaldehyde and subsequent epoxidation of 2 with hydrogen peroxide. 3 reacts with nucleophiles under ring transformation to 4,5‐dihydro‐4‐hydroxy‐1H‐pyrazole‐4‐carboxylic acid derivatives 5. In three cases the intermediate 6 was isolated. 5b, c undergo by dehydrogenation with chloranil rearrangement to 4,5‐dihydro‐4‐oxo‐1H‐pyrazole‐5‐carboxylic acid derivatives 7b, c. magnified image
Eine umlagerung S‐substituierter cyclohexanonthioxime
Authors: Andreae Siegfried , Schmitz Ernst , Schulz Burkhard
Published: July 2007

A Rearrangement of S‐Substituted Cyclohexanone Thioximes

Mercaptoheterocycles like 2‐mercaptobenzazoles 5, 2‐mercaptouracils 10, and ketene S,S‐acetals 18 are aminated by 1‐oxa‐2‐azaspiro[2.5]octane (1). The intermediate cyclohexanone thioximes, which can be isolated in some cases (6a–c, 11), undergo a 1,3‐shift of the mercapto fragment from the nitrogen to the carbon atom followed by cyclization and/or hydrolysis. Thus, new heterocyclic systems as 14–17 or 19 can be created. magnified image
Das trans‐decalingerüst als Abstandshalter für axial konfigurierte Diamine: Herstellung eines phosphatbindenden Bis(guanidins)
Authors: Gross Ralf , Bats Jan W. , Göbel Michael W.
Published: July 2007

trans‐Decalin as a Spacer for Axially Configurated Diamines: Preparation of a Phosphate Binding Bis(guanidinium) Compound

A new type of bis(guanidinium) compound 2 is described which was prepared from trans‐decalin spacers bearing nitrogen substituents in axial positions. Starting from 2, 7‐dimethoxynaphthalene, a sequence of three Birch reductions produced gram amounts of the saturated intermediate and established the stereochemistry of the decalin framework. Guanidinium salt 2a turned out to be a good receptor molecule for phosphoric acid diester anions. However, the catalytical influence on phosphoryl transfer reactions is only weak. magnified image
A short synthesis of (6R)‐6‐methyl‐3‐octanone
Authors: Pawar Archana S. , Chattopadhyay Subrata , Mamdapur Vasant R.
Published: July 2007

A short and efficient synthesis of the title pheromone in optically pure form was developed by starting from R‐citronellol as the chiral template. The salient features of the synthesis were the use of easily accessible inexpensive materials/reagents and operationally simple reactions. magnified image
Verwertung industrieller Abfallstoffe, 1. Synthese neuer, chiraler primärer und sekundärer, 1,2‐Diamine
Authors: Stingl Klaus , Martens Jürgen
Published: July 2007

Utilization of Industrial Waste Materials, 1. – Synthesis of New Primary and Secondary Chiral 1,2‐Diamines

Primary and secundary 1,2‐diamines with three or four stereogenic centers were synthesized starting from the benzyl ester of the bicyclic proline analogue (all‐R)‐2‐azabicyclo[3.3.0]octane‐3‐carboxylic acid [(all‐R)‐2b] by a four‐ or five‐step procedure. This is an example for the utilization of the industrial waste material (all‐R)‐2b. magnified image
Glycal‐1‐ylmethylphosphonates – precursors of glycosyltransferase inhibitors
Authors: Frische Klaus , Schmidt Richard R.
Published: July 2007

Direct lithiation of 2‐phenylsulfinyl‐ and 2‐phenylsulfonylsubstituted galactal derivatives 3a–c and subsequent reaction with DMF gave 1‐C‐formyl derivatives 4a–c. Reduction afforded hydroxymethyl derivatives 5a–c which were transformed into mesylates 7 and 9, respectively. Treatment with trimethyl phosphite furnished phosphonates 8 and 10; by treatment with sodium in liquid ammonia and subsequent reaction with acetic anhydride in pyridine both compounds were converted into monomethyl galactal‐1‐ylmethylphosphonate (11) which could not be completely demethylated without structural change. O‐Acetyl‐protected mesylate 18, obtained from galactosyl cyanide in a few steps, was transformed into bromide 19 which on treatment with P(OSiMe3)3 gave bis(trimethylsilyl) phosphonate 20. Reaction with NaOMe/MeOH afforded the unprotected disodium salt of D‐galactal‐1‐ylmethylphosphonate 1. Similarly, from L‐fucopyranosyl cyanide 22 the corresponding target molecule 2 was obtained. magnified image
Novel concepts in directed biaryl synthesis, XXXVII. Synthesis and enantiomerization of a nonracemic 2‐hydroxy‐2′‐biarylcarbaldehyde, a probable intermediate in the atropo‐enantioselective ring opening of biaryl lactones
Authors: Bringmann Gerhard , Hartung Thomas
Published: July 2007

The directed preparation of a “free”, i.e. nonprotected biaryl with a phenolic OH function and a formyl group in opposite ortho positions, in a nonracemic form, is described. The free activation barrier ΔG≠ for the atropisomerization, which was determined to be 99.2 kJ mol−1, is far lower than expected for an exclusively physical rotation process and is more likely in agreement with an isomerization via lactol‐type cyclic intermediates previously postulated. magnified image
Selektive Synthese ortho‐disubstituierter Tetrahydroanthracene mit Retinoidstruktur
Authors: Hanefeld Wolfgang , Jung Manfred
Published: July 2007

Selective Synthesis of ortho‐Disubstituted Tetrahydroanthracenes with Retinoid Structure

A synthesis of analogues of Temarotene (Ro 15‐0778) (1) is described. This synthesis achieves the selective substitution in ortho‐positions of a tetrahydroanthracene system using palladium‐catalyzed coupling techniques. magnified image
Synthese, Strukturaufklärung und Reaktionen trans‐verknüpfter 3, 6‐Anhydro‐1, 2‐O‐isopropyliden‐α‐D‐hexofuranosen
Authors: Reckendorf Wolfgang Meyer Zu , Schultz Norbert , Kreimeier Richard
Published: July 2007

Synthesis, Structure Elucidation and Reactions of trans‐Fused 3, 6‐Anhydro‐1, 2‐O‐isopropylidene‐α‐D‐hexofuranoses

Unexpectedly, the reaction of 1, 2‐O‐isopropylidene‐5, 6‐di‐O‐(p‐tolylsulfonyl)‐α‐D‐allofuranose (7) with KCN in ethanol yielded the first trans‐fused 3,6‐anhydro‐hexofuranose 10. Besides by spectroscopic evidence the structure of 10 was proved by transformation to the tosylated acetal 13 which could also be obtained via an independent route. Further reactions of 10 all resulted in opening of the strained ring system yielding acetals (18–22). By blocking the 5‐position with the alkali‐resistant ether function this cyclization could also be achieved by more common reagents like NaH in DMF (32). – By applying this procedure to the corresponding α‐D‐galactofuranose derivative 41 3,6‐anhydro‐α‐D‐galactofuranose 42 could also be obtained albeit in low yield. For comparison purposes the 3,6‐anhydro‐α‐D‐gulo derivative 47 was synthesized from easily accessible 44. magnified image
Amination of Some Nitroisoquinolines with Liquid Methylamine/Potassium Permanganate
Authors: Woźniak Marian , Nowak Krystyna
Published: July 2007

5‐Nitro‐, 3‐methyl‐5‐nitro‐, 5, 7‐dinitro‐, 5‐chloro‐8‐nitro‐ and 8‐chloro‐5‐nitroisoquinoline (1a–e) as well as 5‐nitroisoquinoline N‐oxide (1f) are aminated with a liquid methylamine solution of potassium permanganate (LMA/PP) to the corresponding mono‐ or mono‐ and bis(methylamino)‐substituted nitro compounds 2 (a–m). 1‐Nitroisoquinoline (1g) is aminated with LMA/PP to 1‐(methylamino)isoquinoline (2n). Quantum‐chemical calculations for some mononitroisoquinolines suggest that, in general, the experimentally observed regioselectivity of the amination is controlled by an interaction of frontal molecular orbitals (FMO) of the reagents. magnified image
2‐Trifluormethyl‐substituierte Aminosäuren, 19. 2‐Trifluormethylaminosäureester, Bausteine für Trifluormethyl‐substituierte Harnstoff‐, Thioharnstoff‐Derivate und andere potentielle Wirkstrukturen
Authors: Burger Klaus , Schierlinger Christian , Hollweck Wolfgang , Mütze Kerstin
Published: July 2007

2‐Trifluoromethyl‐Substituted Amino Acids, 19. – 2‐Trifluoromethyl α‐Amino Acid Esters, Building Blocks for Trifluoromethyl‐Substituted Ureas, Thioureas and Other Potential Biological Active Structures

The preparative value of trifluoromethyl‐substituted building blocks increases with the number of additional functionalities present. 2‐Trifluoromethyl α‐amino acid esters 2 represent readily available starting materials, excellently suited for the introduction of the biologically interesting trifluoromethyl group into a variety of classes of compounds, like ureas 4 and thioureas, acylureas 5 and acylthioureas 12, imidazolidin‐2,4‐diones 8 and imidazolidin‐4‐on‐2‐thiones 11 as well as 2‐isocyanatoalkanoic acids 13. Via the latter Fmoc‐2‐trifluoromethyl α‐amino acid 16a can be readily prepared. magnified image
2‐Trifluormethyl‐substituierte Aminosäuren, 20. N‐ und C‐terminaler Einbau von α‐Trifluormethyl‐substituierten α‐Aminosäuren in Azapeptide
Authors: Burger Klaus , Schierlinger Christian , Mütze Kerstin , Hollweck Wolfgang , Koksch Beate
Published: July 2007

2‐Trifluoromethyl‐Substituted Amino Acids, 20. – Incorporation of α‐Trifluoromethyl‐Substituted α‐Amino Acids into the N‐ and C‐Terminal Position of Azapeptides

Coupling reactions of α‐trifluoromethyl‐substituted α‐amino acids and azaamino acids via α‐isocyanatocarboxylic acid derivatives are described. magnified image
Sterically Congested Molecules, 11. The 2,6‐Diisopropylphenyl Substituent at CC and CN Groups
Authors: Knorr Rudolf , Ruhdorfer Jakob , Böhrer Petra , Bronberger Hildegard , Räpple Edith
Published: July 2007

Two series of new compounds with sterically shielded, sp2‐hybridized C‐α atoms are prepared from bromo(chloro)‐2,6‐diisopropylbenzene. The α‐(2,6‐diisopropylphenyl) substituent common to all of them is used as an NMR‐spectroscopic indicator for the ease of aryl‐α single‐bond rotation. The corresponding ΔG≠ values are >23.8 kcal/mol with methyl or bromine as additional α substituents at a CC bond, but <8.5 kcal/mol with α‐H. The analogous 2,6‐diisopropylacetophenone imine has ΔG* = 18.0 kcal/mol while the N‐substituted imines prefer the (Z) conformations with ΔG≠ > 23.3 kcal/mol, and ΔG≠ ≈ 31.5 kcal/mol for the (Z)‐hydrazone. Comparisons of these data with reaction conditions show that chemical transformations are not seriously impeded unless they depend on reagent attack at a π face of the C‐α atom in a CC or CN group which rotates slowly about the bond to 2,6‐diisopropylphenyl. magnified image
Unerwartete Reaktion von gemischten Azinen von Dihydrocodeinon mit Methansulfonsäure
Authors: Schmidhammer Helmut , Schwarz Peter
Published: July 2007

Unexpected Reaction of Mixed Azines of Dihydrocodeinone with Methanesulfonic Acid

By treatment of the mixed azines 7 and 8 with methanesulfonic acid in dimethyl sulfoxide the corresponding pyrroles 9 and 10 were not obtained. In both cases the main product was the pyrrole 11, which was also synthesized from dihydrocodeinone azine (12) by reaction with methanesulfonic acid in dimethyl sulfoxide. magnified image
Asymmetric Synthesis of ent‐Corey Lactone Alcohol and its 12‐(all‐cis)‐ and 11‐Epimers via Free Radical 5‐exo‐trig‐C, C Cyclization
Authors: Mulzer Johann , Kermanchahi Abdul Kader , Buschmann Jürgen , Luger Peter
Published: July 2007

Asymmetric eight‐step syntheses are reported for the ent‐Corey lactone alcohol derivatives 3a–d and their epimers 4a–d and 14a, b from (R)‐2,3‐isopropylidene glyceraldehyde (5) as the starting material. The key step of the synthesis is the free radical cyclization of the butenolide thiocarbonates 11, 12 and 13. This reaction produces 3 and 4 in ratios between 57:43 and 30:70 from 11 and 12, whereas 14a and 14b are generated from 13 in a ratio of 19:81. From 3d the prostanoid enone 18 is prepared via the configurationally stable aldehyde 17. magnified image
Synthesis of Dipeptides Containing Novel Cyclopropyl‐ and Cyclopropenyl‐Substituted β‐ and γ‐Amino Acids
Authors: Paulini Klaus , Reißig Hans‐Ulrich
Published: July 2007

The N‐silylated methyl 2‐aminocyclopropanecarboxylate 1 can be incorporated into a dipeptide via a CsF‐mediated condensation reaction with N‐tosylated phenylalanine chloride 5. Due to its instability the corresponding free β‐amino acid 4 could not be isolated up to now, and peptides containing this structural element have previously not been accessible. After desilylation, the aminomethyl‐substituted cyclopropane or cyclopropene derivatives trans‐ 10, 12, and 13 also provided N‐protected dipeptides in good yields. magnified image
Cyclopropandiamine, 4. Synthese und 1H‐NMR‐Spektren diastereomerenreiner 1,2‐Cyclopropandiamine und 1,2‐Cyclopropandiammonium‐dibromide
Authors: von der Saal Wolfgang , Reinhardt Robert , Seidenspinner Hubert‐Matthias , Stawitz Josef , Quast Helmut
Published: July 2007

Cyclopropanediamines, 4. – Synthesis and 1H‐NMR Spectra of Pure Diastereomers of 1,2‐Cyclopropanediamines and 1,2‐Cyclopropanediammonium Dibromides

The efficient preparation of pure diastereomers of N,N′‐(1,2‐cyclopropanediyl)diurethanes 16–18 and ‐diammonium dibromides 4, 19, and 20 is reported. Curtius rearrangement of cis‐ and trans‐1,2‐cyclopropandicarboxylic dihydrazides 14 yields di(O‐benzyl) diurethanes 16 on a 10‐100 g scale. The cis‐1,2‐cyclopropanedicarboxylic dihydrazides cis‐14 tend to form bicyclic products. Thus, from cis‐14a a small amount of 22a is obtained besides the diurethane cis‐16a. Cyclisation is the main reaction in the case of cis‐1,2‐dimethyl‐1,2‐cyclopropanedicarboxylic hydrazide (cis‐14e) which affords the bicyclic products 22e and 24, but no diurethane. The 1,2‐dimethyl‐1,2‐cyclopropanedicarboxylic acid (27) reacts with diphenyl phosphorazidate to produce the monobenzyl ester 29. The diurethanes 16 are methylated (→ 17) and benzylated (→ 18) at both nitrogen atoms. The benzyloxycarbonyl group is removed from the diurethanes 16–18 by the action of hydrogen bromide in acetic acid to yield the 1,2‐cyclopropanediammonium dibromides 4, 19, and 20. The 1H‐NMR spectra are analysed and the results are employed as criteria for the configurations. magnified image
Tetrahydrofurane und γ‐Lactone, VII. Synthese und Reaktionen von γ,γ‐disubstituierten γ‐Lactonen – ein Weg zu funktionalisierten Dodecandisäure‐Derivaten
Authors: Tochtermann Werner , Weidner Fritjof
Published: July 2007

Tetrahydrofurans and γ‐Lactones, VII. – Synthesis and Reactions of γ,γ‐Disubstituted γ‐Lactones – an Approach to 4,5‐Functionalized Dodecanedioic Acid Derivatives

The title compounds 5 are obtained by Diels‐Alder reaction of cyclooctyne and 2‐substituted furans, subsequent hydrogenation, ozonolysis and oxidation with air. The lactone ring of 6c is opened by treatment with sodium iodide and zinc to give the methylene carbonyl derivative 9a. Compound 9a is converted into the cyclopropane 13 via the pyrazoline 12. magnified image
Vicarious Nucleophilic Substitution (VNS) of Hydrogen in Azulenes
Authors: Ma̧goikosza Mieczyslaw , Kuciak Renata , Wojciechowski Krzysztof
Published: July 2007

Azulene reacts with carbanions bearing a leaving group according to the vicarious nucleophilic substitution (VNS) scheme. Treatment of 6‐chloroazulene with such carbanions affords the VNS reaction and nucleophilic aromatic substitution (SNAr) products. magnified image
Pheromone Synthesis, CLXII. Synthesis of Methyl 2,6,10‐Trimethyltridecanoate, the Male‐Produced Pheromone of the Stink Bugs, Euschistus heros and E. obscurus, as a Stereoisomeric Mixture
Authors: Mori Kenji , Murata Noriaki
Published: July 2007

Methyl 2,6,10‐trimethyltridecanoate (1), the male‐produced attractant pheromone of the South American soybean pest, Euschistus heros, and that of E. obscurus, was synthesized as a stereoisomeric mixture and identified by a comparison with the natural product on the basis of GC and MS data. magnified image
The 2‐(Chloroacetoxymethyl)benzoyl (CAMB) Group as a Novel Protecting Group for Carbohydrates
Authors: Ziegler Thomas , Pantkowski Guido
Published: July 2007

The application of the 2‐(chloroacetoxymethyl)benzoyl (CAMB) group to the O‐protection of position 2 in glycosyl donors is described. Saponification of the phthalide and subsequent chloroacetylation of 2‐(hydroxymethyl)benzoic acid (1) gave 2‐(chloroacetoxymethyl)benzoic acid (2). Treatment of 2 with thionyl chloride afforded the acyl chloride 3. Acylation of O‐2 of 1,3,4,6‐tetra‐O‐acetyl‐α‐D‐glucopyranose (4a), galactopyranose (4b) and of the amino group of 1,3,4,6‐tetra‐O‐acetyl‐2‐amino‐2‐deoxy‐β‐D‐glucopyranose (4c) afforded the fully protected pyranose derivatives 5a–c in high yields. Compounds 5a and 5b were converted with HBr in acetic acid into the corresponding 2‐O‐CAMB‐protected bromides 6a, b in excellent yields. Silver trifluoromethanesulfonate promoted glycosylation of the latter with 2‐hydroxyethyl benzoate yielded the β‐glycosides 8a (74%) and 8b (69%). Direct activation of the glucosamine derivative 5c with ferric chloride gave the glucoside 8c (54%). Furthermore, the galactosyl bromide 6b was coupled with methyl 2,3,4‐tri‐O‐benzoyl‐β‐D‐glucopyranoside (11) affording the 2′‐O‐CAMB‐protected methyl glycoside disaccharide 12 (63%). Similarly, condensation of the glucosyl bromide 6a with 4a gave the β‐(1→2)‐linked disaccharide 13 (45%). Treatment of compounds 8a and 13 with thiourea resulted in the deblocked glycosides 9a and 14. Similar deprotection of 8b gave 2‐benzoyloxyethyl 3,4,6‐tri‐O‐acetyl‐β‐D‐galactopyranoside (9b) and the 2‐O‐[2‐(hydroxymethyl)benzoyl] derivative 10. Reaction of 8c with thiourea afforded solely the dechloroacetylated glucoside 9c. magnified image
Stereoselective Synthesis of Steroids and Related Compounds, III. Synthesis of Enantiomerically Pure Hexahydro‐1H‐indenes and Substituted Cyclopentanes as Intermediates for the Synthesis of Steroids
Authors: Groth Ulrich , Taapken Thomas
Published: July 2007

The indene derivative 7 and the 1,2,2,3‐tetrasubstituted cyclopentane derivative 8 have been synthesized in three steps starting from the Hajos‐Wiechert ketone 1. magnified image
Synthesis and Oral Uptake Studies of Lipidic and Glyco‐Lipidic Conjugates of β‐Lactam Antibiotics
Authors: Toth Istvan , Hughes Richard A. , Dekany Gyula , Hillery Anya M. , Ward Peter
Published: July 2007

Lipidic and glyco‐lipidic cephalosporin conjugates 1c and 1i were synthesised as diastereomeric mixtures to improve their oral absorption. 2‐(tert‐Butoxycarbonylamino)tetradecanoic acid was condensed with thiazole 1d and by following basecatalysed hydrolysis of the fully protected rac‐1e, the free acid rac‐1f was produced. This was then used to acylate the carboxy‐protected cephalosporin analog 1g by using a modified Vilsmeier reaction. Removal of the protecting groups of 1b resulted in conjugate 1c. Cephalosporin conjugate li, which contains a sugar moiety in addition to a lipidic amino acid residue, was synthesised to produce a drug conjugate with both lipophilic and hydrophilic properties [radiolabelled (14C) analogs 1a, 1c and 1i were also synthesised]. The radio‐labelled parent 1a and conjugates 1c and 1i were administered orally to rats and uptake of the radiolabel in the blood, various organs, urine and faeces was determined. The results showed that an increase in lipophilicity caused an increase in the oral uptake, suggesting that conjugation to lipidic amino acids and peptides is a useful approach to the improvement of the absorption of poorly absorbed drugs. magnified image
Stereoselective Synthesis of Steroids and Related Compounds, V. Synthesis of (±)‐Chokol A by a Tandem Michael‐Addition/Dieckmann Cyclization
Authors: Groth Ulrich , Halfbrodt Wolfgang , Köhler Thomas , Kreye Paul
Published: July 2007

A total synthesis of (±)‐chokol A (rac‐12) was accomplished in five steps by starting from the α,β‐unsaturated ester (E)‐2 in an overall yield of 24%. The key step of this synthesis is the tandem conjugate addition/Dieckmann cyclization of the cuprate derived from vinyl bromide 9 with the α,β‐unsaturated ester (E)‐2.
The First Synthesis of Azapterocarpans and Azaisoflavans: A Convenient Route to 3‐Aryl‐1,2,3,4‐Tetrahydroquinolines
Authors: Tőkés Adrienne L. , Antus Sándor
Published: July 2007

The first synthesis of the 5,6,6a,11a‐tetrahydro[1]benzofuro[3,2‐c]quinolines (5‐azapterocarpans) 1–4 has been achieved by palladium‐catalyzed arylation of the appropriately substituted 1,2‐dihydroquinolines 15, 16. The 5‐azapterocarpans 3 and 4 have been transformed into the 3‐aryl‐1,2,3,4‐tetrahydroquinolines (azaisoflavans) 24 and 26, respectively, by reduction with Red‐Al®.
Chiral Polymethine Dyes, III. Synthesis and Spectroscopic Properties of an Unsymmetrical, Chiral Monomethine Cyanine Dye with a Thiazolyl and Quinolyl End Group
Authors: Reichardt Christian , Budnik Ulrich
Published: July 2007

The synthesis of the unsymmetrical monomethine cyanine dye 6 in its monochiral (6a, b) and isochiral form (6c), first realized by Götze in 1938, has been significantly improved and its spectroscopic properties have been studied. According to the synthetic pathway, the stereogenic center in dye 6 is delivered by monochiral 1‐phenylethylamine.