bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of 22‐Cupriosteroids, a New Route to Steroids Possessing Oxygenated Side Chains
Authors: Scherlitz‐Hofmann Ina , Bößneck Ulrich , Schönecker Bruno
Published: June 2010

A new method for the synthesis of steroids with oxygenated side chains starting from C22 steroids is described. Rieke copper, obtained by reduction of lithium 2‐thienylcyanocuprate 4 with lithium naphthalenide at −78°C or −100°C, reacts with the 22‐bromosteroids 1a, 2, 14 to afford the corresponding cupriosteroids. In addition to the metalation a very smooth retro Diels‐Alder reaction takes place in the case of 14 at the B ring. The steroid‐copper compounds react with (±)‐1,2‐epoxypropane to furnish epimeric mixtures of the 24‐hydroxysteroids 6, 8 and 15 in good yields. The procedure described is useful for a short synthesis of (24R)‐cholesta‐5,7‐diene‐3β,24,25‐triol (17, as 3‐silyl ether), the provitamin of the main metabolite (24R)‐24,25‐dihydroxyvitamin D3, using 14, Rieke copper and the highly functionalized chiral building block 10/n‐butyllithium.
New Compounds from 6,7‐Dihydrobenzo[c]thiophen‐4(5H)‐ones.
Authors: Prim Damien , Joseph Delphine , Kirsch Gilbert
Published: June 2010

The reactivity of the ketone moiety in 6,7‐dihydrobenzo[c]‐thiophen‐4(5H)‐ones 1 was used to generate new benzo[c]‐thiophene derivatives. The behaviour of the ketones under Vilsmeier‐Haack‐Arnold conditions was studied. Generally, the reactivity of the ketone moiety is shown to be dependent on the substituents of the thiophene ring.
On the Reaction of Nitrilium Salts with Secondary Carboxamides
Authors: Hitzler Martin G. , Lutz Martin , Shrestha‐Dawadi Prativa Bade , Jochims Johannes C.
Published: June 2010

Nitrilium salts 1, the first products of the Beckmann rearrangement of oximes, react with secondary amides 2, the final products of this rearrangement, to afford mixtures of up to four different N‐acylamidinium salts 3–6 (mechanism Scheme 4). The ratio 3/4/5/6 depends on the configuration of 2, the substituents of 1 and 2, the reaction temperature and the concentrations of the reactants. With tertiary amides nitrilium salts give only one N‐acylamidinium salt, the formation of which is also explained by the mechanism of Scheme 4. An X‐ray structural analysis in reported for the product obtained from 2‐pyridone and N‐isopropylbenzonitrilium hexachloroantimonate. First cyclic nitrilium salts (1d, k, w) were prepared.
Synthesis of Protected 4‐Deoxyaklanonic Acid via Naphthalene‐substituted Oligoketides
Authors: Krohn Karsten , Schäfer Gisbert
Published: June 2010

Ketide side chains (C4) were attached to the naphthoquinone 3 by reaction with the dienes 4 or 14 followed by Baker‐Venkataraman rearrangement of esters 8 and 17 to attach the second protected β‐diketo side chain. Linear anellations of the corresponding naphthoquinone precursors 9 and 17 to the 4‐deoxyaklanonic acids 10 and 18a, respectively, were effected in a base‐catalyzed cascade of reactions (e.g. only three operations from 3 to 18a).
Donor‐substituted oligothiophenes, 1 synthesis and properties of a series of methylthio oligothiophenes
Authors: Bäerle Peter , Götz Günther , Synowczyk Andreas , Heinze Jürgen
Published: June 2010

A homologous series of donor‐substituted oligothiophenes 7–9 bearing methylthio groups in the „outer”︁ β‐positions were synthesized up to a quaterthiophene. The physical properties are dependent on the chain length of the conjugated system. The compounds exhibit biological activities. Due to the substitution pattern, even the longer oligomers exhibit good film‐forming properties and could be electropolymerized to the corresponding donor‐substituted polythiophenes P7–P9 with a stereoregular structure. The electronic properties were found to be dominated by the donor strength of the substituents.
A Simple Route to New Macrocyclic Ligand Skeletons: Syntheses and Crystal Structures of Poly(ethoxycarbonyl)[3n]phanes
Authors: Meiners Christian , Vögtle Fritz , Nieger Martin
Published: June 2010

New types of macrocyclic complexing agent precursors with [3n]phane molecular skeletons were synthesized by reaction of 1,3‐bis(bromomethyl)arenes with sodium ethyl malonates. After chromatographic separation, the eighteen‐membered trimethoxy[33]metacyclophane II1a together with the twentyfour‐membered tetramethoxy[34]metacyclophane II2a and the twentyfour‐membered [34](2,6)pyridinophane I2a could be isolated as crystalline compounds. The crystal structures of I2a, II2a, and III1a were determined by single‐crystal X‐ray structure analyses. The presented syntheses of the proposed molecular skeletons of metacyclophane type II and pyridinophane type I provide a facile route to substituted macrocycles which can be easily converted into polyacids with manifold substitution patterns.
The Cubane Cage – a Sensible Probe for Substituent Effects on a Four‐membered Ring
Authors: Irngartinger Hermann , Strack Stefan , Gredel Frank
Published: June 2010

The crystals of methyl 4‐fluoro‐1‐cubanecarboxylate (1), methyl 4‐chloro‐1‐cubanecarboxylate (2) and methyl cubanecarboxylate (5) are isomorphous to each other as are the crystals of methyl 4‐bromo‐1‐cubanecarboxylate (3) and methyl 4‐iodo‐1‐cubanecarboxylate (4). As a result of the space groups P21/m and Pnma, respectively, all molecules lie in a crystallographic mirror plane. Therefore, the methoxycarbonyl group is exactly planar, and the carbonyl fragment is in an eclipsed position to the cubane skeletal bond C2–C7. The electronic effects of the halogen atoms, in particular fluorine and chlorine, give rise to a shortening of the vicinal skeletal bonds. In contrast, the methoxycarbonyl groups causes a lengthening of the vicinal skeletal bonds C2–C6 and C2–C6A which are not in an eclipsed conformation. Ab initio calculations at the 6–31G level of compounds 1, 2, and 5 confirm the experimental results.
Ring Closure of 4‐Azido‐3‐formyl‐(or Acetyl‐)2‐pyridones to Isoxazolo[4,3‐c]pyridones
Authors: Khattab Ahmed F.
Published: June 2010

Azidation of the chlor aldehyde 2, which was obtained from the 4‐hydroxy‐2‐pyridone 1, afforded the ring‐closed isoxazolopyridone 3. Thermolysis of the 3‐acetyl‐4‐azido‐2‐pyridone 8, which was obtained from the corresponding 4‐tosyloxy derivative 7, afforded isoxazolopyridine 9. Amination of the chloro aldehyde 2 yielded the pyrido[4,3‐b]quinoline 11 instead of the 4‐chloroazomethine 10.
Verbotene Reaktionen, II Die disrotative Cyclobuten‐Ringöffnung
Authors: Roth Wolfgang R. , Rekowski Volker , Börner Sabine , Quast Michael
Published: June 2010

Forbidden Reactions, II. – The Disrotatory Cyclobutene Ringopening

The energy profiles for the con‐ and disrotatory opening of benzocyclobutene, methylenecyclobutene, and cyclobutene derivatives were established by NO and oxygen trapping. The enthalpy for the transition states for the forbidden reactions proved to be identical with the heat of formation of the orthogonal diradicals derived by geometrical isomerization of the dienes formed in these reactions. These diradicals describe very well the activation barriers observed for the disrotatory opening of bicyclic cyclobutenes ([3.2.0] and [2.2.0] systems), but not for bicyclo[2.1.0]pent‐2‐ene, indicating here a truly forbidden reaction.
Deamination Reactions, 58. Stereoselectivity of 2‐Methyl‐2‐norpinyl Cations
Authors: Herrmann Roland , Kirmse Wolfgang
Published: June 2010

Optically active (1S)‐1‐methylbicyclo[2.2.1]heptan‐2‐one (25) was prepared by starting from (1R)‐bicyclo[2.2.1]heptan‐2‐one (21). Photolysis of the tosylhydrazone 8 of 25 generates, in part, 1‐methylbicyclo[2.2.1]heptane‐endo‐2‐diazonium ions (10) from which 1‐methylbicyclo[2.2.1]heptan‐endo‐2‐ol (14) and 2‐methylbicyclo[3.1.1]heptan‐2‐ol (16) arise. The ee of both products (42–45%) was found to agree within experimental error. These data point to the bridged 2‐methyl‐2‐norpinyl cation (13) as the most stable structure. Racemization of 13 via the open 2‐methyl‐2‐norpinyl cation (17) as the transition state competes with nucleophilic capture.
A Convenient Synthesis of (4R,7Z,11Z)‐(‐)‐4‐Methylheptadeca‐7,11‐dienal and (4R,7Z,11Z)‐4‐Methylheptadeca‐7,11‐dienoic Acid
Authors: Sharma Anubha , Chattopadhyay Subrata
Published: June 2010

A synthesis of the title aldehyde 1 and acid 2, the (R) enantiomers of the antifungal and antibacterial principles of Sporothrix species, was developed. Alkylation of the alkynol derivative 6 with (S)‐citronellyl bromide (5), depyranylation, cis hydrogenation, PCC oxidation, and Z‐selective Wittig reaction with hexylidenephosphorane gave the hydrocarbon 11. Its regioselective epoxidation and cleavage of the epoxide with HlO4 affords (R)‐1 which was oxidized to (R)‐2.
Lipase‐Catalyzed Regio‐ and Enantioselective Esterification of rac‐1,2‐O‐Cyclohexylidene‐myo‐inositol
Authors: Rudolf Marco T. , Schultz Carsten
Published: June 2010

The hydroxyl group at C‐5 in racemic 1,2‐O‐Cyclohexylidene‐myo‐inositol (rac‐1) was regio‐ and enantioselectively acylated to give 5‐O‐acetyl‐ (2a)‐ or 5‐O‐butyryl‐2,3‐O‐cyclohexylidene‐myo‐inositol (3a), respectively, by treatment of 1 with vinyl acetate or 2,2,2‐trifluoroethyl butyrate in the presence of crude porcine pancreatic lipase in various organic solvents. Compound 2a was phosphorylated and deproted to give myo‐inositol 1,4,6‐trisphosphate (8). Compound 2a was deacetylated and the resulting 2,3‐O‐cyclohexylidene‐myo‐inositol (1) was converted to myo‐inositol 1,4,5,6‐tetrakisphosphate (6).
Studies with Altrose Derivatives – A Convenient Approach to α‐Linked Digitoxosides
Authors: Miethchen Ralf , Rentsch Daniel
Published: June 2010

The 2‐O‐(cyclohexylcarbamoyl)‐3,4‐O‐(2,2,2‐trichloroethylidene)‐protected α‐altropyranosyl fluorides 1, 7, and 11 were used as starting materials for intra‐ and intermolecular glycosylations in the presence of BF3. Because of the effective neighbouring group participation of the carbamoyl moieties, the corresponding trans‐glycosides 2, 4, 6, 12, and 14 can be stereoselectively prepared from 1 and 11, respectively, in good yields. In the case of the 6‐O‐formyl derivative 7 the intramolecular glycosylation to 1,6‐anhydro‐2‐O‐(cyclohexylcarbamoyl)‐3,4‐O‐(2,2,2‐trichloroethylidene)‐β‐D‐altropyranoside (8) is possible, when no other competing nucleophiles are present. Furthermore, the deoxygenation of the altrose moiety of 6‐O‐[6‐deoxy‐3,4‐O‐(2,2,2‐trichloroethylidene)‐α‐l‐altropyranosyl]‐1,2: 3,4‐di‐O‐isopropylidene‐α‐D‐galactopyranose (15) in 2‐position and the hydrogenolysis of the trichloroethylidene acetal protecting group were simultaneously realised. 6‐O‐(2,6‐Dideoxy‐3,4‐O‐ethylidene‐α‐l‐ribo‐hexopyranosyl)‐1,2:3,4‐di‐O‐isopropylidene‐α‐D‐galactopyranose (16) was obtained by reduction of the intermediately prepared 2‐xanthate of 15 with Bu3SnH/AIBN.
Azo Bridges from Azines, XIX. Intramolecular \documentclass{article}\pagestyle{empty}\begin{document}$ \left[ {\sigma _{\rm s}^2 + \pi _{\rm s}^2 } \right] $\end{document} Photocycloaddition Reaction of Parallel Three‐Membered Rings with Azo Groups
Authors: Hünig Siegfried , Schmitt Michael
Published: June 2010

[3 + 2] Photocycloaddition reaction of three‐membered rings with azo groups were accomplished for the first time by photochemically induced π,π* excitation of several systems of the general typeCEexemplified by1,3,5,7,10,13, and17. Intramolecular reaction of the parallel arranged functional groups yields cage compoundsFH(2,4,6,8,11,14, and18) in a [σs2+ πs2] process, SystemsCEare inert on n,π* excitation in aprotic solvents. In methanol or better 2‐propanol, however, the azo groups are reduced from their triplet states. The resulting hydrazino groups, also available by catalytic hydrogenation, open the aziridine rings of7,10, and13as well as the oxirane ring of17by nucleophilic attack, producing the half cages9,12, and19.
Azo Bridges from Azines, XX.
Authors: Brand Uwe , Hünig Siegfried
Published: June 2010

Introduction of a cyano group into the olefinic bridge of 10 (type A) leads to the formation of 16 (type C) in high yield. To obtain 16 first 10 is transformed into isoxazoline 11 which is opened to hydroxy nitrile 12 (type B) from which after brosylation (15) 16 is isolated. Reduction of the azo bridge in 15 affords half cage 13. Smooth oxidation of 12 yields oxo nitrile 19, from which under basic conditions another half cage (18) results. Unexpectedly, on heating with triethylamine 19 undergoes complete rearrangement of the bridges, 21 being formed on release of strain. The course of this reaction which has to pass through a cage with a diazetidine moiety is discussed.
Biologically Active Glycosides from Asteroidea, XXXIV. Isolation and Structure of Cerebrosides from the Starfish Stellaster equestris
Authors: Higuchi Ryuichi , Harano Yoichiro , Mitsuyuki Mika , Isobe Ryuichi , Yamada Koji , Miyamoto Tomofumi , Komori Tetsuya
Published: June 2010

Biologically Active Glycosides from Asteroidea, XXXIV. – Isolation and Structure of Cerebrosides from the Starfish Stellaster equestris

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O‐Glycoside Synthesis under Neutral Conditions in Concentrated Solutions of LiClO4 in Organic Solvents Employing Benzyl‐Protected Glycosyl Donors
Authors: Böhm Gerd , Waldmann Herbert
Published: June 2010

The benzyl‐protected glucosyl trichloroacetimidates, phosphates, and halides 1 are activated under neutral conditions and without the addition of any further promoter in 1 M solutions of LiClO4 in ether, CH2Cl2, CHCl3, or CH3CN and react under these conditions with the model alcohols 3 to give the glycosides 4 in moderate yields. If the α‐imidate 1a or the β‐phosphate 1d is used as glycosyl donor, in the majority of the cases 1:1 mixtures of the anomers are obtained. In contrast, the β‐imidate 1b gives a distinct excess of the α‐glycosides and if the α‐phosphate 1c is employed, the β‐anomers are formed preferentially. Whereas the glycosyl chloride 1f and the glycosyl bromide 1e are not the donors of choice under these conditions, from the β‐fluoride 1g the desired O‐glycosides are readily obtained. In 3–5 M solutions of LiClO4 in ether instead of the expected glycosides benzyl‐protected 1,6‐anhydroglucose 6 is formed and the imidazolylcarbonylactivated carbohydrate 1h reacts with the alcohols 3 to give the glycosyl carbonates 5. Whereas CH2Cl2 and CHCl3 do not influence the stereoselectivity of the glycosylations in ether or CH3CN, the solvent seems to participate in the steric control of the O‐glycoside formation.
Regioselectivity in SNH Reactions of Nitroquinolines with Chloromethyl Phenyl Sulfone
Authors: Grzegożek Maria , Woźniak Marian , van der Plas Henk C.
Published: June 2010

3‐Nitro‐, 4‐nitro‐, 7‐nitro‐, 5,7‐dinitro‐, and 6,8‐dinitroquinoline react with the carbanion of chloromethyl phenyl sulfone to give products of substitution of hydrogen at positions 4, 3, 8, 6,8, and 5,7, respectively. The reactions are found by quantum chemical calculations to be controlled by the interactions of the HOMO of the nucleophile with the LUMO of the substrate. The σ adducts 4‐(methylsulfonylphenyl)‐3‐nitroquinoline and 3‐(methylsulfonylphenyl)‐4‐nitroquinoline are detected by 1H‐NMR spectroscopy. In addition, heats of formation of the intermediary σ adducts 2a–d, f, h, and i are calculated.
Inverse and Normal [4 + 2] Cycloadditions of a 4a,8a‐Methanophthalazine to Azirines and 1,2,4‐Triazoline‐3,5‐dione as Heterodienophiles
Authors: Laue Jörg , Seitz Gunther
Published: June 2010

The 4a,8a‐methanophthalazine 4 is a novel propellane containing an electron‐rich cyclohexadiene and an electron‐deficient diazadiene system within the same molecule. The highly strained azirines 6 and 9a–c, prepared from the corresponding vinyl azides 5 and 8a–c, undergo cycloaddition in situ to the diazadiene system of 4 to furnish the stable polycyclic azo compounds 7c and 10–12 which possesses exo configuration at the annulated aziridine. Attack apparently occurs from the less hindered face, anti to the methano bridge of 4 with high stereo‐ and site selectivity. The electron‐deficient 1,2,4‐triazoline‐3,5‐dione 13 reacts with the electron‐rich diene of the azo compound 12 to yield the anti‐anti bisadduct 14.
1,2:5,6‐Di‐O‐isopropylidene‐α‐D‐gulofuranose as a Chiral Auxiliary in the Diastereoselective C Methylation of Ester Enolates. The Influence of the Base on the Stereochemistry of Enolate Formation and Alkylation
Authors: Mulzer Johann , Hiersemann Martin , Buschmann Jürgen , Luger Peter
Published: June 2010

The C methylation of the carbohydrate‐derived O‐chiral esters 5a‐d to derivatives 8 proceeds with (R) selection of 1:1 to 10:1 and depends primarily on the base used for enolate generation. Lithium 2,2,6,6‐tetramethylpiperide (LTMP) shows the highest and lithium hexamethyldisilazanide (LHMDS) the lowest selection. These results are interpreted in terms of a “post‐enolization complex” involving the lithium amide base.
Syntheses, Structures, and Complexation Properties of Photoresponsive Crownophanes
Authors: Fürstner Alois , Seidel Günter , Kopiske Carsten , Krüger Carl , Mynott Richard
Published: June 2010

A set of tethered bis‐benzophenone or ‐benzaldehyde derivatives was subjected to intramolecular McMurry reactions, thus affording hybrids with cyclophane and crown ether substructures (“crownophanes”). All macrocycles were formed in reasonable yields even at rather high concentrations. A comparative study showed that low‐valent titanium [Ti] exerts a strong template effect whereas alkali metal salts accumulating during its preparation have only little influence upon the preorganization of the substrates in a favorable podand‐like conformation. Ester linkages in the tethers turned out to be only partly compatible with the reaction conditions. Crystal structures of crownophanes 7, 8, and 12 are described. A 1H‐ and 13C‐NMR study on the complexation of Ag(+1) by 8 and 10 revealed that the endocyclic arene entities rather than the polyether chains are the major sites of interaction of the cation with its host.
Conformational Analysis of Benzoannulated Nine‐Membered Rings, 5. 1,2,6,7‐Tetrahydro‐4H‐3,5‐benzodioxonin
Authors: Rys Barbara , Szneler Edward , Duddeck Helmut
Published: June 2010

Temperature‐dependent 1H‐ and 13C‐NMR spectra of the title compound are presented. Coalescence effects are discussed and assigned to two dynamic processes: (a) ring inversion of the nine‐membered ring, (b) racemization of the enantiomeric ground‐state conformations of the nine‐membered ring. The barriers are 52 and 35 kJ mol−1, respectively. The stability of the ground state conformation is discussed in terms of transannular hydrogen interactions and anomeric effects. An assignment of the proton signals in the groundstate conformation is proposed.
A Versatile Domino Synthesis Affording Novel S‐ and U‐Shaped Terpyridines. – Synthesis, Properties and Crystal Structure
Authors: Keuper Ralf , Risch Nikolaus , Flörke Ulrich , Haupt Hans‐Jürgen
Published: June 2010

The development of a simple and general method for the preparation of multifunctional terpyridines is described. The treatment of the ketones 1a–g with ternary iminium salts results in the formation of the isomeric terpyridines 6 and 8 (according to a domino reaction). A possible reaction mechanism is discussed. In some cases the isolation of the postulated dihydropyridine intermediates was successful. The isolation of the 1,4‐dihydropyridines 5e, 5j, and 5r (donor‐substituted) is surprising, because most of the stable dihydropyridines are acceptor‐substituted. In several cases the yields of such domino reactions are very high (>80%). Whether Sor U‐shaped terpyridines are formed is immediately recognized by NMR spectroscopy. Some special cases (8c, 8e, 6h) were investigated by means of single‐crystal X‐ray analysis.
Synthesis of Sterically Fixed Podophyllotoxins
Authors: Laatsch Hartmut , Ernst Bernd Peter , Noltemeyer Mathias
Published: June 2010

Podophyllotoxin and epi‐podophyllotoxin derivatives (1/2) with an unsaturated side chain at C‐5a were obtained by C‐alkylation of protected derivatives of 1. The azide 3a afforded 4 in quantitative yield at 80°C. With pyridine/acetyl chloride, the latter yielded the rigid epi‐podophyllotoxin derivative 7, whose structure was established by crystal structure analysis. All reported podophyllotoxin derivatives are less cytotoxic than podophyllotoxin (1a) itself.
Microwave‐Assisted Carbonyl Diels‐Alder and Carbonyl‐Ene Reactions Supported on Graphite
Authors: Garrigues Bernard , Laurent Régis , Laporte Christian , Laporterie André , Dubac Jacques
Published: June 2010

“Dry” carbonyl Diels‐Alder and carbonyl‐ene reactions with microwaves and reactants supported on graphite were dramatically accelerated with respect to homogeneous conditions both involving classical or microwave heating. Although the reactions were carried out in an open reactor, a control of the evaporation of volatile reagents was possible, probably due to their retention or confinement by graphite.
Novel Dienes and Dienophiles, VI. On the Chemical Behavior of 2‐Ethynyl‐1,3‐butadiene
Authors: Hopf Henning , Jäger Helge , Ernst Ludger
Published: June 2010

The behavior of 2‐ethynyl‐1,3‐butadiene (1) as the diene component in Diels‐Alder additions has been studied using a selection of representative double and triple bond dienophiles. The latter include maleic anhydride (5a), diethyl fumarate (6), benzoquinone (7), methyl acrylate (11), juglone (20), 1‐methylcyclopropene (23), dimethyl acetylenedicarboxylate (26), propiolic aldehyde (32), 4‐phenyl‐1,2,4‐triazolin‐3,5‐dione (35) and diethyl azodicarboxylate (37). [2 + 4] Cycloadducts were formed in all cases in varying yields. The addition is accompained by thermal dimerization of 1 which leads to 1,4‐diethynyl‐4‐vinyl‐1‐cyclohexene (43) and 1,6‐diethynyl‐1,5‐cyclooctadiene (39). The mechanism of this dimerization is discussed. In a competition experiment towards maleic anhydride (5a), diene 1 was shown to be ca. five times less reactive than isoprene.
Syntheses of β‐Lactones, 6. One‐Step Synthesis of β‐Lactones by Aldolization of Ketones or Aldehydes with 1‐Acylbenzotriazoles
Authors: Wedler Christine , Kleiner Katharina , Kunath Annamarie , Schick Hans
Published: June 2010

Benzotriazolides 1 of alkanoic acids with one hydrogen atom in α‐position to the carboxamide group can be deprotonated with lithium diisopropylamide or lithium hexamethyldisilazanide to amide enolates 2 which condense at −90 to −95°C with ketones or aldehydes 3 to afford benzotriazolides of O‐lithiated β‐hydroxylalkanoic acids 4. These reactive carboxamide derivatives cyclize with elimination of lithium benzotriazolide to the corresponding di‐ and trisubstituted β‐lactones. With regard to the formation of β‐monosubstituted β‐lactones from aldehydes the use of benzotriazolides as active carboxylic acid derivatives proved to be superior to the application of the corresponding phenyl esters. An α‐unsubstituted β‐lactone 6 was obtained from 1‐acetylbenzotriazole only with cyclohexanone. The other carbonyl compounds 3 did not provide the corresponding α‐unsubstituted β‐lactones 6.
Utilization of Industrial Waste Materials, 6. Utilization of Derivatives of the Bicyclic Proline Analog (all‐R)‐Octahydrocyclopenta[b]pyrrol‐2‐carboxylic Acid in the Stereoselective Synthesis
Authors: Wilken Jörg , Wallbaum Sabine , Saak Wolfgang , Haase Detlef , Pohl Siegfried , Martens Jürgen , Patkar Laxmikant N. , Dixit Arun N. , Chittari Pabba , Rajappa Srinivasachari
Published: June 2010

Utilization of the industrial waste material benzyl (all‐R)‐cyclopenta[b]pyrrol‐2‐carboxylate 1a or its derivatives 1b, 1c as chiral auxiliaries is described. Allylation of nitrothioacetamides, proceeding by initial S‐allylation followed by a facile thio Claisen rearrangement, is accomplished with a diastereomeric ratio (dr) up to 85:15 using 1a, b as auxiliaries in stoichiometric amounts. Another aspect of this report is the diastereoselective synthesis of optically active amines, starting from aldehydes, with optical purities (op) up to 99%, Again a derivative of 1a was used as source of chirality.
Antibiotics from Gliding Bacteria, LXXV. Absolute Configuration and Biosynthesis of Tartrolon B, a Boron‐Containing Macrodiolide from Sorangium cellulosum
Authors: Schummer Dietmar , Schomburg Dietmar , Irschik Herbert , Reichenbach Hans , Höfle Gerhard
Published: June 2010

The absolute configuration of tartrolon B (1), a boron‐containing macrodiolide from Sorangium cellulosum, was established by X‐ray structure analysis as (2R,3R,4R,7S,8S,11S). Compared to the related boron‐containing macrodiolides boromycin (2), aplasmomycin (3), and borophycin (4), and identical substructure and configuration of the boron‐binding site was found for all four compounds. The biosynthesis of 1 was investigated by feeding experiments with 13C‐labeled precursors. According to NMR analyses, the carbon atoms from C‐1 to C‐18 are derived from acetate units, the two methyl groups at C‐22 and C‐23 are derived from methionine, and a three‐carbon starter unit C‐19 to C‐21 is derived from glycerol. The biosynthesis of 1 is closely related to those of 2 and 3 but with respect to the origin of the starter unit it is more distant to that of 4.
Antibiotics from Gliding Bacteria, LXXVI. Vioprolides: New Antifungal and Cytotoxic Peptolides from Cystobacter violaceus
Authors: Schummer Dietmar , Höfle Gerhard , Forche Edgar , Reichenbach Hans , Wray Victor , Domke Tobias
Published: June 2010

The antifungal and cytotoxic metabolites vioprolides A‐D (1–4) were obtained from the myxobacterium Cystobacter violaceus strain Cb vi35 by fermentation in the presence of the adsorber resin XAD‐1180. Peptolide structures 1–4 composed of eight amino acids and a glyceric acid were determined by spectroscopic methods and total hydrolysis. The absolute configurations of the building blocks were established by GC analysis on chiral stationary phases. Common building blocks of 1–4 are l‐Ala, l‐Cys, D‐Leu, l‐Thr, l‐MeVal, (E)‐dehydrobutyrine (E‐Dhb), and l‐glyceric acid (l‐Gla). Two variable positions are occupied by l‐Pro or l‐Homopro and l‐Pro or trans‐(2S,4R)‐4‐methylazetidinecarboxylic acid [(2S,4R)‐Maz]. Two defined isomers of 1 were detected in CDCl3 in a ratio of 3 : 2 (2D‐1H NOESY) and assigned to rotational isomers at the amide bond of ThrMeVal.
Chiral Lactols, XIV. Stereoselective Fusion of Five‐Membered Ring Lactols to the Bornane Ring System
Authors: Noe Christian R. , Knollmüller Max , Gärtner Peter , Mereiter Kurt , Steinbauer Gerhard
Published: June 2010

Condensation of d‐camphor (b) with diethyl oxalate and subsequent ester hydrolysis yielded camphoroxalic acid 3. endo‐Fused lactone 9 was obtained by reduction of 3 with zinc followed by reduction with NaBH4 and ring closure with H2SO4. exo‐Fused lactone 16, the crystal structure of which was determined, was prepared by reduction of 3 with NaBH4 under basic conditions followed by catalytic hydrogenation and ring closure with HCl. Reduction of 9 and 16 with DI‐BALH and application of acidic work‐up conditions yielded the self‐condensed reduction products (lactol anhydrides) 10 and 17, which are useful reagents in racemate resolution and stereoselective synthesis.
Oligophenylene Rods: A Repetitive Approach
Authors: Liess Petra , Hensel Volker , Schlüter A.‐Dieter
Published: June 2010

The concept of repetitive synthesis was successfully applied to oligophenylenes. A series of monodisperse rigid‐rods with up to 16 phenylene rings and with defined functional groups at both termini was prepared using the Suzuki cross‐coupling reaction.
Synthesis of Sphingosine Relatives, XVIII!. Synthesis of Penazetidine A, an Alkaloid Inhibitor of Protein Kinase C Isolated from the Marine Sponge Penares sollasi
Authors: Yajima Arata , Takikawa Hirosato , Mori Kenji
Published: June 2010

Two stereoisomers of penazetidine A (1a), the azetidine alkaloid isolated from the Indo‐Pacific marine sponge Penares sollasi, were synthesized by starting from (S)‐serine and (R)‐or (S)‐citronellol. The natural penazetidine A must be either (2S,3R,4S,12′R)‐ or (2S,3R,4S,12′S)‐1a.
Pigments of Fungi, 65! Synthesis of Haematopodin – a Pigment from the Mushroom Mycena haematopus (Basidiomycetes)
Authors: Hopmann Cordula , Steglich Wolfgang
Published: June 2010

Haematopodin (1), a pigment from fruit bodies of the mushroom Mycena haematopus, was synthesized from 6,7‐bis‐(benzyloxy)indole (5). Key steps in the synthesis were the addition of 3‐[(2,4‐dimethoxybenzyl)amino]‐1‐propanol (11) to the indolo‐6,7‐quinone 10 and cyclization of the resulting adduct 12 with trifluoroacetic acid.
anti‐Selective Aldol Reactions of Amino Acid Ester Enolates. Application to the Synthesis of α‐Alkylated β‐Hydroxy Amino Acids
Authors: Grandel Roland , Kazmaier Uli , Nuber Bernhard
Published: June 2010

Deprotonation of N‐protected esters of the amino acids alanine 1, ethylglycin 6, valine 7, and phenylalanine 8 with LDA and subsequent addition of various metal salts result in the formation of a probably chelated metal enolate. Aldol reactions of these enolates with aldehydes afford the anti isomers of α‐alkylated α‐amino‐β‐hydroxy acids in a highly diastereoselective fashion. Best results are obtained with titanium enolates, bulky aliphatic aldehydes, and sterically demanding amino acids.
Dithio and Thiono Esters, 64. Attempted Synthesis of Bis(alkylthio)‐Orthoqinodimethanes from Dithiobenzoates
Authors: Hartke Klaus , Bien Notker , Massa Werner , Wocadlo Sigrid
Published: June 2010

o‐Alkyl substituted dithiobenzoates 3 are S‐methylated with trimethyloxonium tetrafluoroborate to form the stable bis(alkylthio)arylmethylium tetrafluoroborates 4. Their deprotonation with LiHMDS takes place either at the o‐alkyl groups to form the postulated o‐quinodimethanes 5 as intermediates or at the SMe groups to give the thiocarbonyl ylides 7. Both intermediates dimerize to furnish either the dibenzo[a,e]cyclooctenes 6 or the 1,4‐dithianes 8/9. Their trapping with N‐phenylmaleimide (10) leads to the formation of the cycloadducts 11 or 12. The structure of 8e was confirmed by X‐ray analysis. p‐Substituted dithiobenzoates 13 show a similar reaction sequence. Their bis(methylthio)arylmethylium salts, however, are only deprotonated at one of the SMe groups to give the 1,4‐dithianes 15/16. Sterically crowded 1,4‐dithianes (e.g. 8d,e/9d,e) rearrange with traces of acid to the ring opened stilbenes 18 and 19.
(Z)‐ und (E)‐Enole von diarylsubstituierten β‐Ketocarbonsäurederivativen
Authors: Buß Monika , Mayer Axel , Müller Klaus , Meier Herbert
Published: June 2010

(Z) and (E) Enols of Diaryl‐Substituted β‐Ketocarboxylic Acid Derivatives

Thermolysis of the 1,3‐diaryl‐2‐diazo‐1,3‐propanediones 4 in the presence of alcohols or amines yielded the compounds 7–11 which exist as chelated (Z) enols or as tautomeric ketones. Contrary to the steric interaction of two mesityl groups the steric interaction between two naphthyl or two anthryl groups or between naphthyl and mesityl is not sufficient to stabilize the corresponding (E) enols. The latter isomers were generated in irradiation processes of some (Z) enols. Detailed NMR studies were performed in order to characterize the enols and their molecular dynamics.
Synthesis of Medium‐Size Macrocycles by Cinnamate [2 + 2] Photoaddition
Authors: König Burkhard , Leue Stefanie , Horn Clemens , Caudan Arnaud , Desvergne Jean‐Pierre , Bouas‐Laurent Henri
Published: June 2010

Unsaturated macrocycles were obtained by [2 + 2] photoaddition of acyclic biscinnamates. The orientation of the chromophores by ortho‐xylyl (2) or aryl‐1,2‐diynyl (6) spacers leads to the formation of photoproducts in solution as single stereoisomers in high yield. The analogous photocyclization of a cis‐enediyne biscinnamate 4 was less efficient, because of a rapid photochemical isomerization of the central double bond.
Synthetic Studies of Glycosyl Serines in the Carbohydrate‐Protein Region of Protoglycans
Authors: Tamura Jun‐Ichi , Neumann Klaus W. , Ogawa Tomoya
Published: June 2010

A series of glycosyl serines 1–6 which are located in the carbohydrate‐protein linkage region of proteoglycans, including the chondrottin penta‐ and heptasaccharides GalNAcα(1–4)R (3), GalNAcß(1–4)R (4) and GalNAcß(1–4)GlcAß(1–3)GalNAc(1–4)R (6) as well as the heparin pentasaccharide GlcNAcα(1–4)R (5) [R = GlcAß(1–3)Galß(1–3)Galß(1–4)Xylß‐Ser] were systematically synthesized as follows. Trisaccharide acceptor 27 having a Gal(1–3)Galß(1–4)Xyl sequence was glycosylated with di‐ and tetrasaccharide donors 16α, 16ß, 22, and 26, which correspond to the non‐reducing end sequences of 3–6, regio‐ and stereoselectively to afford penta‐ and heptasaccharides 30, 34, 36, and 39, respectively. After the conversion into the respective penta‐ and heptaosylimidates 42c‐f as well as tri‐ and tetraosylimidates 42a and b, they were coupled with serine derivative 43 to give tri‐, tetra‐, penta‐, and heptaosyl serines 44a‐f. All the glycosyl serines were deprotected to 1–6.
Novel Dienes and Dienophiles, VII Preparation and Chemical Behavior of 2,3‐Diethynyl‐1,3‐butadiene
Authors: Hopf Henning , Theurig Marcus , Bubenitschek Peter , Jones Peter G.
Published: June 2010

The two 2,3‐diethynyl‐1,3‐butadiene derivatives 1b and 1c were prepared from 2,3‐dichloro‐1,3‐butadiene (26) and the Grignard reagents 19b and 19c by Kumada coupling. Desilylation of 1b provided the parent molecule 1a. The title compounds were used for the preparation of numerous new enediyne systems by [2 + 4] cycloaddition. The dienophiles employed include maleic anhydride (27a), diethyl fumarate (29), tetracyanoethylene (31), diethyl azodicarboxylate (33), and dimethyl acetylenedicarboxylate (35). With p‐quinones such as p‐benzoquinone (44) as dienophiles the expected mono‐and bisadducts are formed which were dehydrogenated to the bis‐ and tetrakis(trimethylsilylethynyl)naphtho‐ and ‐anthraquinones 47 and 48, respectively, by treatment with DDQ. Heating of 1b in THF at 65°C caused dimerization to the 1,5‐cyclooctadiene derivative 56, which was desilylated to 1,2,5,6‐tetraethynyl‐1,5‐cyclooctadiene (59) by treatment with potassium fluoride in DMF. 1b is approximately 15 times less reactive than 2,3‐dimethyl‐1,3‐butadiene (54) towards maleic anhydride (27a).
Zur Energiedelle von Diradikalen, VI. Das Energieprofil der NO2‐Addition an konjugierte Doppelbindungen: Eine Reaktion mit negativer Aktivierungsenergie
Authors: Roth Wolfgang R. , Bastigkeit Thorsten , Börner Sabine
Published: June 2010

On the Energy Well of Diradicals, VI

Part V: Ref. [1]

.
– The Energy Profile for the NO2‐Addition to Conjugated Double Bonds: A Reaction with Negative Activation Energy

From the NO and temperature dependence of the reaction rates of 1,3‐butadiene, styrene, and methylenebenzocyclobutene with NO2 in the presence of NO, the energy profiles for the formation of the primary adducts are derived, which explain the inverse temperature dependence for the disappearance of the substrate at low NO concentrations and allow to calculate the bond strength of the C–NO2 bond (57.9 ± 1.3 kcal · mol−1).
Zur Energiedelle von Diradikalen, VIII. Das Energieprofil der entarteten Methylencyclobutan‐Umlagerung
Authors: Roth Wolfgang R. , Paschmann Volker
Published: June 2010

On the Energy Well of Diradicals, VIII

Part VII: Ref.

.
– Energy Profile of the Degenerate Methylenecyclobutane Rearrangement

From the temperature and oxygen dependence of the trapping rates of the diradicals 4 and 6, recombination enthalpies of 4.7 and 1.8 kcal · mol−1 are derived. These enthalpies agree well with estimates from our reaction force field (5.5 and 2.0 kcal · mol−1). The increasing stereoselectivity in the methylenecyclobutane rearrangement 1a → 1b with electronically less stabilizing substituents (R = Ph, CH3) is related to the decreasing recombination enthalpy of the intermediate diradical 2. This finding can be rationalized from the changing curve of the electronic energy during the recombination.
Diastereo‐ and Enantioselective Synthesis of Lignan Building Blocks by Tandem Michael Addition/Electrophilic Substitution of Lithiated α‐Amino Nitriles to Furan‐2(5H)‐one
Authors: Enders Dieter , Kirchhoff Jochen , Lausberg Vivien
Published: June 2010

Starting from chiral α‐amino nitriles (S,S,R/S)‐3, we prepared β‐aroyl‐γ‐butyrolactones (S)‐5as well as 2,3‐disubstituted γ ‐butyrolactones (S,S)‐ or (R,S,R)‐6in high yields and with high enantiomeric excesses by conjugate addition to butenolide, followed by protonation, α‐alkylation or α‐aldol addition, respectively. The introduction of one up to three stereogenic centers opens a flexible and highly efficient diastereo‐ and enantioselective route to 2,3‐dibenzylated γ‐butyrolactones6, which proved to be important lignan building blocks.
Thermal Rearrangements, XXV. The Automerization of Benzene as A Radical‐Initiated Reaction
Authors: Zimmermann Gerhard , Nüchter Matthias , Hopf Henning , Ibrom Kerstin , Ernst Ludger
Published: June 2010

The thermal isomerization of [1,4‐D2]‐ (3a) and [1,2‐13C2]benzene (1a) has been studied in excess hydrogen at 750–850°C with contact time less than 1.2 s and very low partial pressure in a quartz flow system. In both cases, the main isomerization products are the corresponding meta isomers. The data suggest a radical intramolecular interchange of the benzene carbon atoms by 1,2‐C shifts. The multistep reaction cascade is initiated by H addition to the benzene ring followed by transannular homoallyl rearrangements involving the intermediate formation of bicyclo[3.1.0]hexenyl and cyclopentadienylmethyl radicals. This pathway constitutes a side reaction competing with the direct stabilization of the cyclohexadienyl radicals formed preferentially at high temperature.
Enzymes in Organic Synthesis, 26. Synthesis of Enantiomerically Enriched 2,3‐ and 3,4‐Dimethylpentan‐5‐olides by Lipase‐Catalyzed Regio‐ and Enantioselective Alcoholysis of cis‐ and trans‐2,3‐Dimethylpentanedioic Anhydrides
Authors: Ozegowski Rüdiger , Kunath Annamarie , Schick Hans
Published: June 2010

The enzyme‐catalyzed regio‐ and enantioselective alcoholysis of racemic cis‐ and trans‐2,3‐dimethylpentanedioc anhydride in the presence of Novozym 435 from Candida antarctica afforded two of the eight possible monoesters with an enantiomeric excess higher than 90%. Regioselective reductions of these monoesters with lithium borohydride or borane/dimethyl sulfide furnished four enantiomerically highly enriched dimethylpentan‐5‐olides, which are versatile chiral intermediates.
Monodisperse Dialkoxy‐Substituted Oligo(phenyleneethenylene)s
Authors: Stalmach Ulf , Kolshorn Heinz , Brehm Isabella , Meier Herbert
Published: June 2010

Individual but connected synthetic routes for the preparation of the all‐E‐configured 2,5‐dipropoxy‐substituted oligo(1,4‐phenyleneethenylene)s 1a–g were developed. An increasing number of conjugated stilbene units from n = 1 to n = 11 led to a convergent bathochromic shift (Δλ = λ∞ − λ1 = 127 nm) in the UV/Vis absorption. An exponential function for the convergence of the absorption energies (wavelengths) in conjugated systems is proposed. By a simple extrapolation of this function the effective chain length may be determined.
Electron microscopic observations of Pseudomonas aeruginosa
Authors: Baechler C. A. , Berk R. S.
Published: June 2010

Preparative techniques were developed for the purpose of visualizing, by negative contrast, some of the cytological characteristics of unsectioned cells of Pseudomonas aeruginosa. Concentrated fimbriae free from cells had a length of approximately 1.5 μm and a diameter of 6 nm. Pyocin‐like structures ranging in length from 32‐64 nm with a width of 8.6 nm were “attached” to the terminal ends of a small percentage of these fimbriae. Microtubules and ringlets having a diameter of 10‐20 nm were also visualized in the bacteria. Budding or evagination of cell wall material in multiple units up to 135 nm in length was frequently observed in older cultures grown on agar media.
Some physical and chemical parameters affecting the formation and retention of glutamate pools in a marine psychrophilic bacterium
Authors: Griffiths R. P. , Baross J. A. , Hanus F. J. , Morita R. Y.
Published: June 2010

The release of glutamic acid from the obligate marine psychrophilic bacterium Vibrio marinus MP‐1 under various physical conditions has shown that at least two glutamate pools are potentially present. One, designated amino acid pool one, is loosely bound to the cell and is not found in cells accumulating glutamate by de novo synthesis. The second amino acid pool is more stable and is present in cells that are grown on a minimal salts‐sugar medium.
Mutagenic action of methyl methane sulphonate on the bluegreen alga Anacystis nidulans
Authors: Kumar H. D.
Published: June 2010

Growth of the blue‐green alga Anacystis nidulans treated with methyl methane sulphonate (MMS) at pH 5 or 6 was better than that at pH 7 or 8, both in regard to the duration of the lag‐phase and the growth rate. Toxicity of MMS was directly proportional to the temperature at which the cells had been treated. Growth of cells incubated at 5000 lux during MMS treatment was better than those that had been treated in the dark or at 15000 lux.

Ten successive treatments with MMS were ineffective in significantly shortening the lagphase of treated cells.

The frequency of ultraviolet‐resistant mutants but not of streptomycin‐resistant mutants was substantially increased following single treatment with MMS of 40‐60 minute duration; treatments of longer duration resulted in a steep fall in the number of mutants suggesting thereby that treatments of up to 60 min induce genetic changes which are largely unaccompanied by physiological damage.
Fertilitätsmutanten des Turimycin‐Bildners Streptomyces hygroscopicus IMET JA 6599
Authors: Eritt Inge , Schumann G. , Fleck W. F.
Published: June 2010

In a continuing search for fertility mutants of the turimycin‐producer, Streptomyces hygroscopicus, strain IMET JA 6599, from more than 683 pairs of auxotrophic mutants 19 pairs were found to develop colonies after replica plating on selective media. The frequency of recombinant production in mixed cultures on complex medium varies from 10−6 to 10−2 in different combinations of S. hygroscopicus mutants. Typical frequencies representing the proportion of recombinant colonies from spores and/or fragments of substrate mycelium) and a visual indication of the different fertility levels using the familiar fertility test method are given in Tables and Figures. Additionally, reversion rates of markers and different types of colonies of fertility mutants used in some S. hygroscopicus crosses will be shown.
Ultrastructural alterations at the cell wall and plasma membrane of Candida spec. H induced by n‐alkane assimilation
Authors: Fischer W. , Brückner B. , Meyer H. W.
Published: June 2010

The ultrastructure of n‐alkane‐grown cells of Candida spec. H was investigated by thin sectioning and freeze‐etching techniques. On the plasma membrane shallow depressions could be observed. n‐Alkane deposits were localized within the cell wall and at the plasma membrane. Periplasmic multilamellar structures appear in connection with n‐alkane accumulation. Their participation in hydrocarbon assimilation and the nature of the lamellar structures are discussed.
Dependence of the mycelial growth pattern on the individually regulated cell cycle in Streptomyces granaticolor
Authors: Kretschmer S.
Published: June 2010

The growth behaviour of Streptomyces granaticolor ETH 7437 was studied by the microculture technique. The kinetics of growth and branching were recorded and, since elongation was found to be restricted to apical elongation sites (e‐sites), the rate of elongation per site (α) was determined as well. The mycelia grew exponentially. Initially the growth was dependent on α of the germ tube, but after the start of branching, growth paralleled the exponential increase of the number of branches while α attained a constant average value.

Further, for liquid grown mycelia shown about the same growth kinetics the cellular structure was determined after cell wall staining. Three types of cells could be distinguished: apical branchless cells (20%), non‐apical branchless cells (20%) and non‐apical cells with one branch each (60%). Since both the apical and the branched cells possessed an e‐site, 80% of the cells must have been growing at the time of sampling.

Combining detailed data obtained from both the alive and the stained mycelia a model was elaborated, which may reflect the events taking place on the cellular level during mycelial growth. The model is based on the assumption that each cell behaves as an independent unity with respect to its cell cycle. But, in contrast to the behaviour of single cell bacteria, in mycelia the two daughter cells formed upon division are neither equivalent nor uniform. Here, the sister cells differ in length, shape and possession of an e‐site. Only one of the daughter cells receives the e‐site of the mother cell, while the other starts its own cell cycle by generating a new e‐site at the cylindrical part of its envelope. Regarding the length of sister cells the degree of heterogeneity increases with the age of the corresponding region of the mycelium, and eventually some cells lose the ability to generate an e‐site, i. e. to grow.

With this model the kinetic and structural peculiarities of the mycelial growth of Streptomyces granaticolor can be explained.
Production of glucose isomerase by genus Streptomyces
Authors: Suekane M. , Iizuka H.
Published: June 2010

Screening for glucose isomerases was done using 46 species and 63 strains of Streptomyces type cultures. Glucose isomerase was found in a wide range of these species. The intracellular glucose isomerase of S. olivochromogenes showed the highest fructose conversion ratio. The apparent extracellular glucose isomerase activities were observed for several strains of Streptomyces, Streptomyces venezuelae had the highest apparent extracellular glucose isomerase activity.

The glucose isomerase yield was improved from 1.95 units/ml to 7.5 units/ml by induced mutation and culturing condition studies. This increase isomerase yield has made it possible to produce glucose isomerase industrially.
Effect of temperature on chlorophyll stability of some subaerial blue‐green algae
Authors: Tripathi S. N.
Published: June 2010

Chlorophyll stability index of eight subaerial blue‐green algal species, collected from their natural habitats, i.e., bark of trees, soil and roof‐tops and from cultures, has been determined. The algae from natural habitats showed greater chlorophyll stability compared to those algae from cultures. Among the natural algae, high chlorophyll stability was observed in the algae inhabiting adverse habitats. A slight modification in the method of MURTY and MAJUMDER (1962) for determination of chlorophyll stability index has been made. Here the total percentage loss in the amount of Chl a of heated sample in relation to its unheated sample has been considered as chlorophyll stability index.
Non‐invasive time‐course imaging of apoptotic cells by confocal Raman micro‐spectroscopy
Authors: Zoladek Alina , Pascut Flavius C. , Patel Poulam , Notingher Ioan
Published: June 2010

Confocal Raman micro‐spectroscopy (CRMS) was used to measure time‐course spectral images of live cells undergoing apoptosis without using molecular labels or other invasive procedures. Human breast cancer cells (MDA‐MB‐231) were exposed to 300 µM etoposide to induce apoptosis, and Raman spectral images were acquired from the same cells at 2‐h intervals over a period of 6 h. The purpose‐built inverted confocal Raman micro‐spectrometer integrated an environmental enclosure and wide‐field fluorescence imaging. These key instrumental elements allowed the cells to be maintained under sterile physiological conditions (37 °C, 5% CO2) and enabled viability and apoptosis assays to be carried out on the cells at the end of CRMS measurements. The time‐course spectral images corresponding to DNA Raman bands indicated an increase in signal intensity in apoptotic cells, which was attributed to DNA condensation. The Raman spectral images of lipids indicated a high accumulation of membrane phospholipids and highly unsaturated non‐membrane lipids in apoptotic cells. This study demonstrates the potential of CRMS for label‐free time‐course imaging of individual live cells. This technique may become a useful tool for in vitro toxicological studies and testing of new pharmaceuticals, as well as other time‐dependent cellular processes, such as cell differentiation, cell cycle and cell–cell interactions. Copyright © 2010 John Wiley & Sons, Ltd.