bluuebunny/crossref_metadata_2025 huggingface dataset:
Chelation control by a second nitrogen atom in formal hetero Diels‐Alder reactions of N‐arylimines
Authors: Linkert Frank , Laschat Sabine , Knickmeier Markus
Published: July 2007

Lewis acid‐catalyzed cyclization of proline‐derived N‐arylimines 8 gives the tetracyclic decahydro‐7,7,11‐trimethyl‐in‐dolizino[3,4‐b]quinolines 17a, b in a ratio, which is highly dependent on the coordination number of the acidic catalyst. Whereas monodentate Brønsted and Lewis acids as well as octahedral bidentate Lewis acids preferably gave the all‐trans product 17b, the all‐cis product 17a was obtained by tetrahedral aluminium Lewis acids. In contrast to this chelation‐controlled reversal of diastereoselectivity, mixtures of cis/trans undecahydro‐6,6,10‐trimethyl‐11‐azacyclopenta[a]‐anthracenes 18b‐e, h were isolated from the cyclization of the corresponding cyclopentane‐derived N‐arylimines 16 irrespective of the Lewis acid. Force field calculations support a stepwise iminium ion cyclization under thermodynamic control rather than a concerted hetero‐Diels‐Alder mechanism.
A simple synthesis of functionalized rac‐chlorins via allylboration of porphyrin aldehydes
Authors: Höper Frank , Montforts Franz‐Peter
Published: July 2007

Chlorins rac‐17a, b which bear terminally hydroxy‐substituted butyl side chains were synthesized by allylboration and Claisen rearrangement from readily accessible formylporphyrins 5 and 6. The hydroxyalkyl side chain and the photo‐physical properties of the chlorins rac‐17a, b should open a broad access to chlorins suitable for photodynamic therapy having different residues attached to the hydroxy function. The reported synthetic pathway also should be useful for the synthesis of naturally occurring hydroporphyrins containing geminally dialkylated structural parts and a propionic acid residue on the saturated pyrrole ring.
Synthesis of donor‐substituted 2‐benzopyrans, isoquinolines, and cinnolines with acetal structure
Authors: Wünsch Bernhard , Nerdinger Sven , Höfner Georg
Published: July 2007

At −105°C the aryllithium intermediate 7, which was generated by treatment of the donor‐substituted bromo acetal 6 with n‐butyllithium, was trapped with aromatic and aliphatic aldehydes, with paraformaldehyde, with a ketone, an amide, an imine, and an azo compound to yield the hydroxy acetals 9a–c and 18, the homophthalaldehyde derivative 8, the amino acetal 24 and the hydrazino acetal 28. The acid‐catalyzed ring closure of the hydroxy acetals 9a–c and 18, the amino acetal 24, and the hydrazino acetal 28 provided the 2‐benzopyrans 10a–c, 19 and 20, the isoquinoline 26, and the cinnolines 29 and 30, respectively. Hydrogenolysis (H2, Pd/C) of the benzyl‐protective group led to the phenols 15a–c, 21, 31, and 32. The spiropiperidines 21 and 22 showed a very low affinity for the phencyclidine binding site of the NMDA receptor. In mice weakly sedative effects were caused by application of 21 and 22.
Constituents of tropical medicinal plants, LXIX. The hexalobines, diprenylated indoles from Hexalobus crispiflorus and Hexalobus monopetalus
Authors: Achenbach Hans , Renner Christian , Waibel Reiner
Published: July 2007

Nineteen individual hexalobines (diprenyl‐substituted indoles) were isolated from petroleum ether and dichloromethane extracts of the stem bark of Hexalobus crispiflorus and H. monopetalus, respectively. The structures were established by spectroscopic methods. The absolute configurations result from chiroptical measurements and from chemical interconversions. Various hexalobines exhibit significant antifungal activity.
Lurlene, the sexual pheromone of the green flagellate Chlamydomonas allensworthii
Authors: Jaenicke Lothar , Marner Franz‐Josef
Published: July 2007

The pheromone produced by the female gametes of the green flagellate Chlamydomonas allensworthii to lure the male gametes for sexual fusion is the plastohydroquinone derivative lurlene, (all‐E)‐14‐[2′‐hydroxy‐3′,4′‐dimethyl‐5′‐(1″;‐β‐D‐xylopyranosyloxy)phenyl]‐4,8,12‐trimethyltetradeca‐4,8,12‐trienoic acid (1).
The diastereoselectivity of zirconium alkoxide catalysed Meerwein‐Ponndorf‐Verley reductions
Authors: Krohn Karsten , Knauer Birgit
Published: July 2007

The new variation of the Meerwein‐Ponndorf‐Verley reduction using 1‐[4‐(dimethylamino)phenyl]ethanol (DMAPE) (6) or 1‐tetralol (12) (3 equiv.) as the reducing alcohols and Zr(O‐tBu)4 as the catalyst (0.2 equiv.) is kinetically controlled and highly stereoselective. Preferential axial attack is achieved with the sterically less bulky alcohol 6 in the case of 4‐tert‐butyl‐ and 3‐methylcyclohexanones (1a → 96% axial and 3a → 93% axial attack). The combination tetralol (12)/Zr(O‐tBu)4 behaves as a very bulky reducing agent, and the thermodynamically less stable alcohols 2c (80%) and 4c (92–96%) are formed preferentially in the reduction of 2a and 4b. The fused bicyclic systems 1‐methyl‐2‐tetralone (14a) and flavanone (15a) and the steroids 16a–18a are reduced with high stereoselectivity to the corresponding cis alcohols 14b and 15b and the (β‐alcohols 16b–18b. The stereochemical outcome is in agreement with the Felkin‐Ahn model.
Synthesis and antiviral evaluation of quinazoline, thieno‐[2,3‐d]pyrimidine, and lumazine analogues of 3′‐fluoro‐3′‐deoxythymidine (FLT)
Authors: El‐Barbary Ahmed A. , El‐Brollosy Nasser R. , Abdel‐Bary Hamed M. , Pedersen Erik B. , Stein Paul , Nielsen Claus
Published: July 2007

2,4(1H,3H)‐Quinazolinediones 3a–c, lumazine (3d) and thieno[2,3‐d]pyrimidine‐2,4(1H,3H)‐dione (8) were silylated and condensed with methyl 2,3‐dideoxy‐3‐fluoro‐5‐O‐(4‐phenylbenzoyl)‐β‐D‐erythro‐pentofuranoside (2) by using trimethylsilyl triflate as a catalyst to afford the corresponding cyclic nucleosides 4 and 9 and acyclic nucleosides 5 and 10. Removal of the protecting group from the glycon moiety was achieved in good yields by treatment with sodium methoxide in methanol at room temperature. The new FLT analogues were devoid of activity against HIV‐1 and HSV‐1.
Synthesis of 1‐C‐(2,5‐diphenyl‐3,4‐diarylphenyl)alditols
Authors: Del Valle José L. , Marcaccini Stefano , Torroba Tomás
Published: July 2007

Tetraarylcyclopentadienones 2a–c react with (E)‐3,4,5,6,7‐penta‐O‐acetyl‐1,2‐dideoxy‐1‐C‐nitro‐D‐galacto‐ (1a) and ‐D‐manno‐hept‐1‐enitol (1b) to give 1‐C‐(2,3,4,5‐tetraarylphenyl)‐D‐galacto‐ (3a–c) and ‐D‐manno‐penta‐O‐acetylpentitol (3d‐f), respectively, after decarbonylation and HNO2 elimination from the Diels‐Alder cycloaddition intermediates.
Synthesis and stereostructure of some spiro[morphinan‐6,2′(3′H)‐[1,3,4]oxa(thia)diazolines]
Authors: Somogyi László , Szabó Zoltán , Hosztafi Sándor
Published: July 2007

Treatment of dihydrocodeinone (thio)semicarbazones 1a–d with Ac2O/ZnCl2 afforded (6S)‐spiro[morphinan‐6,2′(3′H)‐[1,3,4]oxadiazolines] (2a, b) and (6R)‐spiro[morphinan‐6,2′‐(3′H)‐[1,3,4]thiadiazolines] (3a, b), respectively. The structure of the products including the configuration of the spiro carbons was determined by 1H‐ and 13C‐NMR measurements.
Umlagerung von 3‐Thioxo‐Δ1,4‐steroiden, ein neuer Zugang zu Steroidthiolen
Authors: Möller Stephanie , Weiß Dieter , Beckert Rainer
Published: July 2007

Rearrangement of 3‐Thioxo‐Δ1,4‐steroids, a New Approach of Steroid Thiols

3‐Thioxoandrosta‐1,4‐dien‐17‐one (1) is subjected to a dienthion‐thiophenol rearrangement in aprotic and protic solvents in the presence of an acid catalyst resulting in the formation of 1‐(acetylthio)‐4‐methylestra‐1,3,5(10)‐trien‐17‐one (2). 1‐mercapto‐4‐methylestra‐1,3,5(10)‐trien‐17‐one (3), and the dimer 1,1′‐(dithio)bis[4‐methylestra‐1,3,5(10)‐trien‐17‐one] (4) as the reaction products. The mercapto compound 3 tends to be autoxidized to the sulfide 4.
A Synthesis of rac‐S‐(2‐Acetoxy‐3‐hexadecyloxypropyl) thiophosphocholine, the isosteric and isopolar PAF analog
Authors: Mlotkowska Barbara , Olejnik Jadwiga
Published: July 2007

rac‐S‐(2‐Acetoxy‐3‐hexadecyloxypropyl) thiophosphocholine (5), the isosteric and isopolar thiophosphate analog of Platelet Activating Factor (PAF), was synthesized from bis(2‐acetoxy‐3‐hexadecyloxypropyl) disulfide (12) or O,O‐diethyl S(2‐acetoxy‐3‐hexadecyloxypropyl) thiophosphate (16) as starting materials by two independent „one‐pot”︁ procedures in 65% and 20% overall yield, respectively.
Azachlorins: Synthesis of a novel type of hydroporphyrins from the bile pigment bilirubin
Authors: Gerlach Benjamin , Montforts Franz‐Peter
Published: July 2007

Azachlorins rac‐10a,b, rac‐11, and rac‐16, a novel type of hydroporphinoid compounds, were synthesized from azaporphyrins 8 and 13 by regioselective cycloaddition of singlet oxygen and further transformation by amide acetal Claisen rearrangement. The azaporphyrins are readily accessible from the naturally occurring bile pigment bilirubin (5). The photophysical properties of the azachlorins recommend these chlorin derivatives as potential photosensitizers for Photodynamic Therapy (PDT).
Common pathways to 1,3,2‐thiazaphospholidin‐4‐ones
Authors: Weber Martin , Ugi Ivar
Published: July 2007

1,3,2‐Thiazaphospholidin‐4‐ones are a relatively new group of five‐membered cyclic phosphorylating agents. They may be used in amino acid phosphorylation and nucleotide coupling. Common pathways to thus compounds are reported. Even sulfurized DNA analogs are accessible by these agents.
Syntheses of putative metabolites of 1,2,3,4‐tetrahydro‐7,12‐dimethylbenz[a]anthracene
Authors: Srivastava Santosh K. , Sharma Pradeep K.
Published: July 2007

Syntheses of (8α,9α,10α,11β)‐trans‐1,2,3,4,8,9,10,11‐octahydro‐7,12‐dimethyl‐8,9‐epoxybenz[a]anthracene‐10,11‐diol (3) and (8α,9α,10β,11α)‐trans‐1,2,3,4,8,9,10,11‐octahydro‐7,12‐dimethyl‐8,9‐epoxybenz[a]anthracene‐10,11‐diol (4), the putative D‐ring metabolites of 1,2,3,4‐tetrahydro‐7,12‐dimethyl‐benz[a]anthracene (1), starting from 1,2,3,4‐tetrahydro‐10‐methoxy‐7,12‐dimethylbenz[a]anthracene (11), are reported.
Synthesis of oxochlorins from the red blood pigment heme and their transformation into potentially biologically active chlorin derivatives
Authors: Bats Jan W. , Haake Gerold , Meier Axel , Montforts Franz‐Peter , Scheurich Gerhard
Published: July 2007

The hydroxychlorinrac‐3was prepared from the readily accessible chlorinsrac‐5a, b. The alcohol function ofrac‐3could be used to attach an estrogen residue28and the hydroquinone19to yield the chlorin estrogen ethers32a, band the chlorin hydroquinone etherrac‐30respectively. The prepared chlorin estrogen derivatives might be useful as sensitizers and fluorescence markers for photodynamic therapy and other diagnostic/therapeutic applications. The chlorin hydroquinone ether is of interest as a potential artificial photosynthesis system, which contains a „natural”︁ chlorin as a structural subunit in contrast to previously synthesized model systems based on porphyrins.
Formation of tricyclic compounds in domino reactions of alkenal oximes
Authors: Aurich Hans Günter , Quintero Jose‐Luis Ruiz , Sievers Ulrich
Published: July 2007

5‐Alkenal oximes 4, 12, and 13 were prepared by various methods. These oximes undergo a domino reaction with mercaptoacetaldehyde (1‐M) affording tricyclic compounds 6, 17 and 18, respectively. At first the mercapto group adds to the oxime function forming a hydroxyamino moiety which then condenses with the aldehyde group giving the cyclic nitrones 10, 15, and 16, resp., as intermediates. These nitrones undergo spontaneously an intramolecular cycloaddition yielding the tricyclic compounds (6, 17, 18). The regioselectivity of the latter reaction step is opposite to that observed for corresponding intermolecular nitrone cycloadditions. The domino reaction proceeds highly selectively affording only one of the diastereomers. Starting from enantiomerically pure oxime 13, we prepared optically active 18. The stereogenic center of 13 induces the formation of three further stereogenic centers in the product. The configuration at C‐5 of 18 was determined by a NOESY experiment.
Synthesis of 5,5,10,10‐tetramethyl‐1‐oxacyclotridecane‐6,7,8,9‐tetrone – on the mechanism of the Rubottom reaction
Authors: Gleiter Rolf , Staib Michael , Ackermann Uwe
Published: July 2007

The synthesis of 5,5,10,10‐tetramethyl‐1‐oxacyclotridecan‐6,7,8,9‐tetrone (12) was achieved via a multistep procedure involving an oxidation known as the Rubottom reaction. The key intermediates were the dialdehyde (25), the diacid (33), the cyclic diketone (39) and the bis(silyl enol ether) (42). The oxidation of 42 with mCPBA yielded two diastereomers, the syn and anti bis(α‐hydroxy ketones) (44, 45) the ratio of which depends strongly on the solvent used. This result combined with the isolation of the diepoxide (43) gives an insight into the stereochemistry of the Rubottom reaction.
Ab initio and semiempirical calculations of the hetero‐Diels‐Alder reaction of 1‐aza‐1,3‐butadiene with ethene
Authors: Tietze Lutz F. , Fennen Jens , Geißler Holger , Schulz Gerhard , Anders Ernst
Published: July 2007

The transition structures of the hetero‐Diels‐Alder reaction of (E)‐ and (Z)‐1‐aza‐1,3‐butadiene (8 and 11) were studied by means of ab initio (UHF/6‐31+G* and RHF/6‐31+G*) and semiempirical (AM1, PM3) methods. The energy surface of the title reaction was calculated with AM1/CI. Two competing reaction channels exist, a concerted and a two‐step path. All methods used show a preference for the two‐step mechanism in agreement with experimental observations.
A novel synthesis of 1‐(2,4,6‐trihydroxy‐3,5‐dimethylphenyl)ethanone (di‐C‐methylphloracetophenone) and two new non‐aromatic C‐benzylated derivatives
Authors: Hauteville Marcelle , Stomberg Rolf , Gaillard Pascale , Duclos Marie‐Christine
Published: July 2007

The synthesis of the title compound 1e was achieved by an easy three‐step procedure from 1,3,5‐benzenetriol (1a, phloroglucinol). Compound 1a was C‐methylated using MeI. The crude mixture obtained was acetylated to give 1d which was converted into 1e using BF3 AcOH complex. Benzylation of the latter with benzyl chloride afforded the new non‐aromatic compound 2. Reaction of 2 with NaOH and benzoyl chloride (Scheme 1) gave the new compound 4. Its structure was established by X‐ray analysis.
Structure elucidation of yersiniabactin, a siderophore from highly virulent Yersinia strains
Authors: Drechsel Hartmut , Stephan Holger , Lotz Ralf , Haag Hubert , Zähner Hans , Hantke Klaus , Jung Günther
Published: July 2007

From cultures of Yersinia enterocolitica H1852, an iron‐complexing and iron‐transporting compound named yersiniabactin was isolated. The structure of the siderophore was determined by a variety of spectroscopic methods, including 2D NMR experiments on the metal‐free ligand as well as its gallium complex. The metal‐free ligand, derivatives, as well as iron and gallium complexes were examined by high‐resolution FAB‐MS, API‐MS, API‐MS/MS and GC‐MS. The novel siderophore contains a benzene and a thiazolidine ring, as well as two thiazoline rings (Figure 1). Its stereochemistry is noteworthy for the presence of five chiral centers, one of which is considerably epimerized. The compound forms stable complexes with trivalent cations such as ferric iron and gallium.
π…︁π interactions of flavins, 5. Syntheses, structures and physical properties of flavin systems with covalent bonding to π donors and π acceptors (quinones)
Authors: Staab Heinz A. , Kanellakopulos Johannes , Kirsch Peer , Krieger Claus
Published: July 2007

To study π…︁π interactions of flavins of different redox states with π‐electron donors and acceptors, the syntheses of compounds in which such π systems are linked to flavins by using the „cyclophane concept”︁ were attempted and partially achieved. The syntheses of the metacyclo‐isoalloxazinophanes 1 and 2 are reported as well as the X‐ray structure analysis of 2. The conversion of 1 or 2 to the benzoquinono‐isoalloxazinophanes 3 or 4, respectively, was not achieved, obviously due to the specific sterical shielding of the methoxy groups in the isoalloxazinophanes. Benzoquinone‐isoalloxazine systems in which the two components are linked by only one triethylene chain were obtained. Spectroscopic and electrochemical properties related to intramolecular interactions are reported.
Sulfonamide‐based catenanes — regioselective template synthesis
Authors: Ottens‐Hildebrandt Stephan , Schmidt Thomas , Harren Jörg , Vögtle Fritz
Published: July 2007

The first catenanes containing sulfonamide units were synthesized. Selective formation of the in/out isomer 7 can be explained by host‐guest interactions that cause a regioselective templating effect. Replacement of O2S‐NH by O2S‐NMe increases the yield significantly (from 10 to 19%). The sulfonamide catenane 7 has a topologically chiral structure.
Total synthesis of ent‐α‐polypodatetraene
Authors: Imamura Paulo Mitsuo , Pantarotto Helder
Published: July 2007

The first stereocontrolled synthesis of the antipode of the natural product ent‐α‐polypodatetraene (ent‐1) was achieved by starting from copalic acid (3).
Synthesis of asymmetrical methyl‐branched chiral ketones from the corresponding homologous wax esters. A new synthesis of the insect pheromone lardolure and of 9‐norlardolure
Authors: Morr Michael , Proppe Christiane , Wray Victor
Published: July 2007

The insect pheromone (2R4R6R,8R)‐4,6,8‐trimethyl‐2‐undecyl formate (lardolure, 7c) and (2R,4R,6R,8R)‐4,6,8‐trimethyl‐2‐decyl formate (9‐norlardolure, 7b) have been synthesized from the corresponding homologous chiral methyl‐branched esters 1b and 1c, which have been obtained from the preengland wax of the domestic goose Anser a. f. domesticus. The intermediate (4R,6R,8R)‐4,6,8‐trimethyl‐2‐undecanone (4c) and (4R,6R,8R)‐4,6,8‐trimethyl‐2‐decanone (4b), the (2R)‐alcohols 5c and 5b, as well as some analogous compounds, have been characterized. 9‐Norlardolure (7b) shows a weak pheromone activity.
PE‐spectroscopic investigation of nonconjugated π,π interactions in (seco)dodecahedradienes — on the route to an experimental ethylene/ethylene cycloaddition reaction coordinate
Authors: Martin Hans‐Dieter , Mayer Bernhard , Weber Klaus , Wahl Fabian , Prinzbach Horst
Published: July 2007

Nature and extent of nonconjugated π,π interactions in (bis)‐secododecahedradienes and (pentagonal, non‐pentagonal) dodecahedradienes with transannular π,π distances ranging from ca. 2.8 to ca. 3.5 Å – representing well defined points on the D2h [π2 + π2] reaction coordinate – were studied by PE spectroscopy. The π,π splitting of 0.68 eV measured at the largest π,π distance of ca. 3.5 Å (1,16‐dodecahedradiene 3a) was attributed to ca. 50% each of through‐space and through‐bond conjugation (analysis of precanonical MOs).
Synthesis of bis(trifluoromethyl)‐substituted olefins: Methods of preparation and properties
Authors: Haas Alois , Lieb Max , Zwingenberger Jörg
Published: July 2007

Several bis(trifluoromethyl)‐ and trifluoromethyl‐substituted alkenes, dienes, arylalkenes, and α,β‐unsaturated derivatives of carbonyl compounds such as tosylhydrazone 5b and diazomethane 5c were prepared. Their reactivity towards a variety of nucleophiles, resulting from the electron‐withdrawing effect of the trifluoromethyl group, was investigated. Depending on the trifluoromethyl‐ and a bis(trifluoromethyl)‐substituted double bond, different regioselectivities were observed in the reaction with morpholinocyclohexene as a nucleophile. An explanation is given on the basis of the 13C‐NMR data.
Lipophilic α‐hydroxybenzylphosphonates as prodrugs of 3′‐azido‐2′,3′‐dideoxythymidine (AZT)
Authors: Meier Chris , Habel Lothar W. , Balzarini Jan , De Clercq Eric
Published: July 2007

The α‐hydroxybenzylphosphonates 1a–1j of the antiviral drug 3′‐azido‐2′,3′‐dideoxythymidine 5 (AZT) as potential lipophilic prodrugs were readily accessible in 49% to 87% yield via a four‐step synthetic pathway introducing the modifications in the aromatic ring system in the last step by making use of intermediate 6. All compounds 1a–1j exhibited higher partition coefficients in 1‐octanol/water than AZT (5). In hydrolysis studies at pH 7.5 we observed that precursors to bioactive compounds were delivered by simple hydrolysis of the lipophilic precursors 1a–1j via two different mechanisms: the phosphonate‐phosphate rearrangement leading to the benzylphosphotriesters 2 and/or the direct cleavage into the di‐AZT phosphonate 6. Both compounds 2 and 6 were further degraded yielding the potentially antiviral active compounds 4 and 8, respectively. The hydrolysis pathway could be controlled by the substitution pattern in the benzylic moiety. Identical hydrolytic behavior of 1 was detected in „biological”︁ hydrolysis kinetics by using a RPMI culture medium containing 10% heat‐inactivated fetal calf serum (FCS). The title compounds 1a–1j exhibited considerable HIV‐1 and HIV‐2 activity in wild‐type CEM/O cells.
Synthesis of anacardic acids
Authors: Zehnter Reinhard , Gerlach Hans
Published: July 2007

The anacardic acids 1–11, isolated from various plants, were synthesized by a new general method. Reaction of the methyl alkynoates 12–18 with 1‐methoxy‐1,4‐cyclohexadiene at 200°C afforded directly the methyl 2‐methoxybenzoates 19–25 with long chain substituents in 6‐position in 74–85% yield. The dienophiles 12–16 were prepared by pyrolysis of the corresponding acylphosphoranes 26–30, the dienophiles 17 and 18 by methoxycarbonylation of the corresponding alkynes 31 and 32 via the hydroxy esters 33 and 34. Demethylation of 19–23 with All3 gave the methyl salicylates 35–39 which could be hydrolized to the anacardic acids 1–4 and 7. Hydrolysis of 24 and 25 provided the hydroxy acids 40 and 41, which were converted by treatment with CBr4/PPh3 into the acids 42 and 43 bearing bromoalkyl side chains. These were transformed into 44–47 by reaction with 1‐hexynyllithium and 1‐octynyllithium. Stereoselective hydrogenation of 44–47 gave 48–51 with (Z)‐alkene side chains. In a similar approach 42 was converted into 52 and then into 53, which gave upon treatment with 1‐pentynylmagnesium bromide or 1‐heptynylmagnesium bromide the acids 54 and 55 with alkadiyne side chains. Stereoselective hydrogenation provided 56 and 57 with (Z,Z)‐alkadiene side chains. The 2‐methoxy group in 48–51, 56, 57 was demethylated by treatment with All3 to give the anacardic acids 5, 6, 8–11.
Synthesis of [1.1.1]Propellanes by Bridging of Bicyclo[1.1.0]butanes
Authors: Werner Markus , Stephenson David S. , Szeimies Günter
Published: July 2007

Several [1.1.1]propellanes were synthesized by bridging the 1,3‐positions of the corresponding bicyclo[1.1.0]butane. The synthesis of 1‐bromo‐3‐(chloromethyl)bicyclobutanes and the bridging were carried out in a one‐pot reaction by addition of 2.0 equiv. of MeLi to 1,1‐dibromo‐2,2‐bis(chlormethyl)‐cyclopropanes 10. Three routes to 10 were investigated: Firstly, the Wittig reaction of 1,3‐dichloroacetone leading to (chloromethyl)allyl chlorides 6 was, with the exception of 6m, successful only with Wittig reagents derived from primary alkyl halides, Secondly, reduction of diethyl alkylidenemalonates with LiAlH4 in benzene afforded carbinols 12 which were converted into 6 by reaction with N‐chlorosuccinimide/dimethyl sulfide. The cyclopropanation of 6 to 10 was achieved by reaction with bromoform/NaOH under phase‐transfer catalysis conditions. Finally, starting from diethyl alkylidenemalonates, the sequence of reduction and cyclopropanation could be interchanged, according to the sequence 11 → 13 → 14 → 10. Propellanes 5b and 3 were reduced with LiAlH4 to bicyclo[1.1.1]pentanes 15b and e. 2‐D INADEQUATE NMR spectra of 5d and 5p indicate that the coupling constants J(13C‐13C) between the bridgehead positions are very small, i.e. 0.47 and 0.53 Hz, respectively.
van‐der‐Waals‐Komplexe, Intermediate monomolekularer Reaktionen
Authors: Roth Wolfgang R. , Hunold Frank
Published: July 2007

van der Waals Complexes, Intermediates in Unimolecular Reactions

Thermolysis of rac‐ and meso‐1,1′,2,2′,3,3′ ‐hexamethyl‐1,1′‐biindenyl and (1E, 5E)‐1,3,4,6‐tetraphenyl‐1,5‐hexadiene in supercritical CO2 in the presence of oxygen allows to identify three types of intermediates, the free radicals (2 and 5) and the equilibrating complexes I and II consisting of radical pairs. From the oxygen dependence of the trapping and rearrangement rates it is shown, that the complex I is the primary thermolysis product, which in contrast to the complex II does not react with oxygen. The temperature dependance of these rates allows to calculate the enthalpy well of the complex II, which agrees well with predictions of our reaction force field.
Asymmetrische Elektrophile α‐Amidoalkylierung, 11. Neue chirale Hilfsgruppen aus (+)‐Camphersäure
Authors: Wanner Klaus TH. , Paintner Franz F.
Published: July 2007

Asymmetric Electrophilic α‐Amidoalkylation, 11. – New Chiral Auxiliaries from (+)‐Camphoric Acid

Herrn Professor Eberhard Reimann mit den besten Wünschen zum 60. Geburtstag gewidmet.

The chiral bicyclic carboxylic acids 3b–e have been prepared in a few steps from camphoric acid. They were designed as new chiral auxiliaries for asymmetric synthesis with chiral N‐acyliminium ions featuring precomplexation as a mechanism for asymmetric induction. Their asymmetric induction was evaluated in alkylation reactions with the enamides 5b–e being performed by addition of HCl and subsequent treatment of the resulting α‐chloro amide with AlEt3. The carboxylic acid 3e turned out to be well suited as a chiral auxiliary providing high asymmetric induction (e.g. 92.9/7.1 with ZnEt2) and moderate chemical yields (66% 12e + 13e) and being easily removed by acid hydrolysis without destruction.
New Synthetic Pathways to Nitrogen Heterocycles
Authors: Laschat Sabine
Published: July 2007

Novel Lewis acid‐catalyzed cyclizations of N‐arylimines and N‐benzylimines derived from amino acids and terpenes allow the diastereoselective preparation of octahydroacridines, indolizino[3,4‐b]quinolines, indolizidines, quinolizidines and piperidines. Although these two types of reactions can be classified as formal hetero‐Diels‐Alder and hetero‐ene reactions respectively, both proceed stepwise via cationic intermediates, which allow stereochemical control via chelate complexes. Stereochemical and mechanistical studies are described briefly.
A Stable Thiazol‐2‐ylidene and Its Dimer
Authors: Arduengo Anthony J. , Goerlich Jens R. , Marshall William J.
Published: July 2007

The synthesis, characterization and X‐ray crystallographic structure determination are described for a stable thiazol‐2‐ylidene 2. This thiazol‐2‐ylidene is the first example of a stable, crystalline carbene in which the singlet carbene center bears a sulfur substituent. The carbene 2 is the closest stable analog of the important thiamin (vitamin B1) carbene. Although the thiazol‐2‐ylidene 2 is sufficiently stable to isolate at room temperature in the absence of moisture and oxygen, it will dimerize to form a normal carbene–carbene dimer {2}2. With the isolation and structure determination of both 2 and {22}, this system is the first in which a stable carbene and its corresponding dimer have been isolated and characterized. Additionally reported is the “reduced” 2H‐thiazoline 2 · H2 in which the former carbene center in 2 has been reduced to a methylene (CH2) group. Thiazol‐2‐ylidenes with smaller groups on nitrogen (e.g. mesityl or methyl) are too unstable to allow easy isolation. The dimer from 3,4,5‐trimethylthiazol‐2‐ylidene possesses a very unusual geometry in which one of the former carbene centers is planar while the second is pyramidal.
Cycloadditions, 25. – Synthesis and Reactions of sec‐N‐Aryl‐2‐methyl‐2,3‐butadienamides
Authors: Himbert Gerhard , Schlindwein Hans‐Jürgen
Published: July 2007

The reaction of 2‐methyl‐2,3‐butadienoyl chloride 1 with the N‐aryl‐ or the N‐hetarylamines, 2a–f and 2g, h, respectively, in the ratio 1 : 2 (or 1 : 1 in the presence of triethylamine) furnishes the corresponding allenamides 3a–h, accompanied by the HCl adducts, the 3‐chloro‐2‐methyl‐3‐butenamides 4a–g, or the 3‐butynamide 5h. Heating of the allenamides bearing a benzenoid (3a–e) or thiophene (3h) nucleus does not generate any defined products; only the amides bearing the 1‐naphthyl (3f) and the furfuryl (3g) moiety undergo an intramolecular Diels‐Alder reaction to give the oligocyclic compounds 6 and 7. However, heating of the benzenoid allenamides 3a–c in the presence of tolyl isocyanate furnishes, via the N‐carbamoyl‐amides 10a–c, the intramolecular Diels‐Alder products 11a–c, whereby the monocyclic arene has functioned as diene. Reaction of 1 with the 2‐aminofuran derivative 2i leads directly to the Diels‐Alder product 9, a 2 : 1 adduct, whereby the initially formed amide 3i and the intramolecular Diels‐Alder product 8 are not isolated.
Balanced Decarboxylation of Aromatic Polyacids – A One‐Step Synthesis of Perylene‐3,4‐dicarboxylic Anhydride
Authors: Langhals Heinz , von Unold Petra , Speckbacher Markus
Published: July 2007

Perylene‐3,4‐dicarboxylic anhydride (3) is prepared from technical grade perylene‐3,4:9,10‐tetracarboxylic anhydride (1) in 25% yield by a partial decarboxylation reaction using noncondensing amines. Perylene‐3‐carboxylic acid (4) and perylene‐3,4‐dicarboxylic imide (5) are prepared in the same way in yields of 24% and 76%, respectively, by a variation of the reaction conditions.
Highly Selective Alkylation of 5‐Amino‐1‐methyl‐1H‐1,2,4‐triazole with 1‐(1‐Chloroalkyl)pyridinium Chlorides under Formation of Novel Geminal Bis(heteroarylium) Salts: A Combined Experimental/MO‐Theoretical Study
Authors: Anders Ernst , Wermann Kurt , Wiedel Bernd , Eynde Jean‐Jacques Vanden
Published: July 2007

1‐[(5‐Amino‐1‐methyl‐1H‐1,2,4‐triazol‐4‐ylium)(alkyl/aryl)‐methyl]pyridinium dichlorides 3a–h [geminal bis(heteroarylium) salts] were synthesized in high yield from 5‐amino‐1‐methyl‐1H‐1,2,4‐triazole (6a) and the 1‐[(alkyl/aryl)chloromethyl]pyridinium chlorides 1a–h under mild, neutral conditions. Analogous reactions of 1a and 1d with the isomeric 3‐amino‐1‐methyl‐1H‐1,2,4‐triazole (6b), carried out to support the spectroscopic analysis of the alkylation products 3a–h, likewise show exclusive alkylation at the N‐4 atom of the 1H‐1,2,4‐triazole ring with formation of the isomeric 1‐[(3‐amino‐1‐methyl‐1H‐1,2,4‐triazol‐4‐ylium)arylmethyl]pyridinium dichlorides 4a and 4d, respectively. Semiempirical MO and ab initio methods have been applied to predict the relative energies of isomers of 6, the activation barriers of the reaction of electrophiles with 6, and the relative energies of some product salts.
Zinc‐Mediated Asymmetric Epoxidation of α‐Enones
Authors: Enders Dieter , Zhu Jiqun , Kramps Laurenz
Published: July 2007

A new efficient method for the asymmetric epoxidation of α‐enones with oxygen in the presence of diethylzinc and a chiral amino alcohol is presented. The epoxidation proceeds in moderate to excellent yields, complete diastereoselectivity and enantiomeric excesses of up to >99% by using enantiomerically pure (1R,2R)‐N‐methylpseudoephedrine 7 as a chiral additive. The amino alcohol auxiliary 7 employed can be almost completely recovered with unchanged enantiomeric purity.
Tris(1‐naphthyl)borane Studied by Laser Flash Photolysis, Matrix Isolation, and Low‐Temperature NMR Spectroscopy: Two Isomers with Significantly Different Triplet Excited State Properties
Authors: Bucher Götz
Published: July 2007

Laser flash photolysis (308 nm) of tris(1‐naphthyl)borane (TNB, 1) in cyclohexane solution yields a transient spectrum that is best interpreted as the superposition of the spectra of two transient species with λmax = 460 nm (transient 1, τ = 10 μs) and λmax = 640 nm (transient 2, τ = 20 μs). Transient 2 also shows some absorption at λ > 800 nm. Both transient species exhibit behaviour typical of triplet excited states. The seemingly paradoxical situation of two long‐lived triplet excited states being generated by excitation of a single compound can be resolved in terms of two isomeric structures of TNB. The activation energy for isomerization is very low and has been calculated (AM1/RHF) to be of the order of 2.7 kcal/mol. Further evidence comes from low‐temperature 1H‐NMR spectroscopy. At T = 183 K, some NMR bands of 1 are significantly broadened, while the shape of other bands remains nearly constant. This indicates that the broadening effect observed is due to the slowing‐down of an intramolecular rearrangement, and not to a general increase in solvent viscosity. The phosphorescence spectrum of 1, matrix‐isolated in Ar at 10 K, consists of three bands, which can be attributed to two different emitting isomers. The corresponding triplet energies differ significantly and are 57.8 and ca. 48 kcal/mol, respectively. The LFP experiments performed with 1 gave no evidence for the formation of the hypovalent boron species 1‐naphthylborene or di‐1‐naphthylboryl radical.
1,4‐cis‐Diaminotetra(di)deoxyheptitols from Tropilidene – a Variable Access to Tropa‐Type Heterocycles
Authors: Falk‐Heppner Manuela , Hugger Uwe , Keller Manfred , Kaiser Clemens , Krieger Richard , Fritz Hans , Prinzbach Horst
Published: July 2007

The synthetic potential of the dianhydrocycloheptenepentols 3 and dianhydrocycloheptaneheptols 4 – ultimately available from tropilidene – as intermediates en route to 1,4‐cis‐diaminotetra(di)deoxyheptitols is studied. With standard bivalent N nucleophiles (methyl‐, benzylamine, hydrazines) the regioselective installation of two (e.g. 9, 34) amino functions has to compete with the generation of variously functionalized tropa‐type 8‐azabicyclo[3.2.1]octanes (e.g. 29, 30, 35, 45, 47). With azide (N) as monovalent nucleophile in unsaturated diepoxides 3 twofold, nearly regiospecific substitution (7) – in competition with [3,3]‐sigmatropic migration (SN2′ substitution) –, in saturated diepoxides 4 regioselective monosubstitution (39) can be achieved.
The First Total Synthesis of Praecoxin B and Pterocarinin C, Two Natural Products of the Tannin Class
Authors: Khanbabaee Karamali , Lötzerich Kerstin
Published: July 2007

Enantiomerically pure diphenic ester 3 was obtained by esterification of acyl chloride 2 with the glucose derivative 1 by kinetic resolution. Hydrolysis of the ester 3, acylation of the free OH groups at C‐4 and C‐6 of the diol 4 with acid 5 followed by irradiation led to the anomerically deprotected α‐ and β‐anomers (7) (4:1). The natural product praecoxin B (8) was obtained by hydrogenative debenzylation. A second member of the ellagitannin group pterocarinin C (11) was obtained from the common intermediate 7 by acylation in the anomeric position to 10 followed by debenzylation.
Physarorubinic acid, a polyenoyltetramic acid type plasmodial pigment from the slime mold Physarum polycephalum (myxomycetes)
Authors: Nowak Alexander , Steffan Bert
Published: July 2007

The polyenoyltetramic acid physarorubinic acid (2) has been isolated from microplasmodia of the slime mold Physarum polycephalum. The structure was elucidated by means of 1D‐ and 2D‐NMR, IR, and UV spectroscopy and mass spectrometry. The stereochemistry was proven by synthesis of the tetramic acid unit and application of circular dichroism. It was shown that plasmodia of a white mutant strain also contain yellow pigments.
Substrate‐Directed Diastereoselective Hydroformylations, 1. Substrate‐Directed Diastereoselective Hydroformylation of Methallylic Alcohols – Development of an Efficient Catalyst‐Directing Group for Rhodium‐Catalyzed Hydroformylation
Authors: Breit Bernhard
Published: July 2007

The development of an efficient catalyst‐directing group based on ortho‐diphenylphosphanyl benzoate (o‐DPPB) for the substrate‐directed, diastereoselective hydroformylation of methallylic alcohols 5 is described. The hydroformylation of methallylic o‐DPPB esters 9 provides the corresponding syn‐aldehydes 10 with diastereoselectivities of up to 96:4. A specific steric demand of the substituent at the stereogenic center of the methallylic derivatives 9 was found to be necessary to achieve a high degree of stereoselectivity. Experiments have been performed that prove that the o‐DPPB group acts as a catalyst‐directing group by reversibly coordinating to the catalyst. The removal of the o‐DPPB group was accomplished by means of alkaline hydrolysis, thereby furnishing the lactols 6. Oxidation of 6 provides the corresponding γ‐lactones 7.
Aziridine‐2,2‐dicarboxylates: Synthesis, Reactions, and Photochromism
Authors: Schirmeister Tanja
Published: July 2007

Dimethyl 3‐[(4‐nitro)phenyl]aziridine‐2,2‐dicarboxylate (3a) represents a new, photochromic aziridine. 3a and related aziridines undergo cycloadditions with dipolarophiles to form five‐membered heterocycles and react with nucleophiles with cleavage of the C2C3 bond.
Synthesis of 4,5‐Disubstituted 1H‐1,3,4,5‐Tetrahydrobenz[cd]indole Derivatives
Authors: Galambos Géza , Csókási Pál , Szántay Csaba , Szántay Csaba
Published: July 2007

Tetrahydrobenz[cd]indole derivatives (51–54) were synthesized from 4‐iodo‐3‐(2′‐nitroethyl)indole (10) via palladium‐catalysed coupling with acetylenes followed by a thiol addition, an oxidation and an intramolecular Michael‐addition.
Investigations on Solid‐Phase Peptide Synthesis in N‐to‐C Direction (Inverse Synthesis)
Authors: Henkel Bernd , Zhang Lianshan , Bayer Ernst
Published: July 2007

The possibility of peptide assembly in the N‐C direction by using HOBt salts of the amino acid 9‐fluorenylmethyl esters has been investigated. The first amino acid derivative has to be coupled with the N‐terminus to the polymer‐bound trityl linker. Determination of the loading with the first amino acid derivative could be carried out according to the same method as for Fmoc‐amino acids on the resin. Kinetic measurements were made of both the coupling of the amino acid derivatives during chain elongation, and the cleavage of the peptide from the resin. Several C‐terminally modified peptides were synthesized with chain elongation being monitored by UV as it is standard practice in peptide synthesis in the usual direction. Particular attention was paid to racemization that may possibly occur.
Two‐ and Three‐Dimensional Tetrathiafulvalene Macrocycles
Authors: Nielsen Mogens Brøndsted , Becher Jan
Published: July 2007

The syntheses and some physical properties (redox potentials) of cyclic tetrathiafulvalenes (TTF) are reviewed. The ring closure is generally performed in one of two different ways: (i) by coupling of 1,3‐dithiol derivatives thereby forming the central fulvene bond, or (ii) by cyclization of a preformed TTF derivative. The second route is very efficient when using the cyanoethyl protection/deprotection method and has made possible the preparation of a number of two‐ and three‐dimensional macrocycles, e.g. mono‐, bis‐ and tetramacrocycles, oligomeric macrocycles and cage‐type molecules. The use of tetrathiafulvalenophanes in supramolecular chemistry is also exemplified in this microreview.
Synthesis of Enantiomerically Pure Cyclopropyl Boronic Esters
Authors: Luithle Joachim E. A. , Pietruszka Jörg
Published: July 2007

The synthesis of enantiomerically pure cyclopropyl boronic esters 12a−d and 13a−d has been achieved. The high‐yielding process involves the condensation of readily available alkenyl boronic acids 1a−d with (2R,3R)‐1,4‐dimethoxy‐1,1,4,4‐tetraphenyl‐2,3‐butanediol (10), Pd(II) acetate catalyzed cyclopropanation with diazomethane, and chromatographic separation of the diastereoisomers. The absolute configuration has been determined by converting 12a−d and 13a−d to the corresponding cyclopropanols (1R,2R)‐4a+b/(1R,2S)‐4c+d and (1S,2S)‐4a+b/(1S,2R)‐4c+d, respectively, compounds that allowed correlations to be made with previously published data.
A DFT Study on the Vinylcyclopropanecarbaldehyde‐to‐2,5‐Dihydrooxepin Hetero‐Cope‐type Rearrangement and on Related Reactions
Authors: Sperling Dirk , Reißig Hans‐Ulrich , Fabian Jürgen
Published: July 2007

The prototypical 1,2‐cis‐vinylcyclopropanecarbaldehyde‐to‐2,5‐dihydrooxepin hetero‐Cope‐type rearrangement was studied by “exact” first‐principle methods. The reaction pathway was examined. The reaction, as well activation energies, was calculated for the unimolecular transformation of vinylcyclopropanecarbaldehyde and various derivatives. The derivatives differ from vinylcyclopropanecarbaldehyde by replacement of the formyl (CHO) by the thioformyl (CHS) or formiminyl (CHNH) group and, in part, by replacement of hydrogen atoms at the substituted carbon atoms of the cyclopropane ring by hydroxyl or formyl substituents. The experimental reaction parameters of vinylcyclopropanecarbaldehyde are surprisingly well reproduced by B3LYP/6‐31G* density functional and MP2/6‐31G* ab initio quantum theoretical calculations. Reactant and product are nearly isoenergetic, while the activation energy amounts to about 25 kcal/mol. In the case of the nitrogen and sulfur containing compounds the isomeric seven‐membered ring structures are considerably favoured over the cyclopropanes. Due to a low calculated activation energy a rapid formation of the 2,5‐dihydrothiepin is expected. Substitution of the hydrogen at the substituted ring carbon atoms in vinylcyclopropanecarbaldehyde by OH and CHO also lowers the barrier and increases, in general, the exothermicity of the reaction. As shown by the reaction energies of isodesmic reactions both reactants and products are stabilized by substitution. However, the seven‐memberd ring compounds are more strongly stabilized than the cyclopropanes. The OH group exerts a different effect depending on whether the linkage is geminal or vicinal to the CX group. The difference is caused by hydrogen bond formation in geminal arrangements. The substituent effects in the cyclopropane series parallel those for the prototypical Cope‐type and Claisen‐type series. The particular feature of the cyclopropane series is the lower stability of the cyclopropanes relative to the corresponding open chain congeners. This is obviously due to the ring strain which over‐compensates for attractive interactions between cyclopropane and the substituents. In consequence, the formation of seven‐membered ring compounds proceeds more easily than the formation of the corresponding compounds in related Cope‐type rearrangements.
Amidine‐Induced Ring Transformation of a Substituted 1,1‐Dioxo‐1,2‐thiazine‐4‐carbaldehyde into New Pyrimidine Derivatives
Authors: Fanghänel Egon , Bartossek Hagen , Baumeister Ute , Hartung Helmut
Published: July 2007

As a masked 1,3‐dicarbonyl compound, the 1,1‐dioxo‐2H‐1,2‐thiazine‐4‐carbaldehyde 1 undergoes ring transformation with amidines to produce 2‐substituted 4‐methyl‐5‐[1‐methyl‐2‐methylthio‐2‐(N‐phenylsulfamoyl)vinyl]pyrimidines 3a–f. For 3b, an X‐ray structure analysis is reported. From the 4‐methyl‐2‐methylthio‐5‐[1‐methyl‐2‐methylthio‐2‐(N‐phenylsulfamoyl)vinyl]pyrimidine (3e), the substituted pyrimidinone 4 is obtained by acidic hydrolysis.
Magnetic resonance imaging for ischemic heart disease
Authors: Sakuma Hajime
Published: July 2007

Cardiac MRI has long been recognized as an accurate and reliable means of evaluating cardiac anatomy and ventricular function. Considerable progress has been made in the field of cardiac MRI, and cardiac MRI can provide accurate evaluation of myocardial ischemia and infarction (MI). Late gadolinium (Gd)‐enhanced MRI can clearly delineate subendocardial infarction, and the assessment of transmural extent of infarction on late enhanced MRI has been shown to be useful in predicting functional recovery of dysfunctional myocardium in patients after MI. Stress first‐pass contrast‐enhanced (CE) myocardial perfusion MRI can be used to detect subendocardial ischemia, and recent studies have demonstrated the high diagnostic accuracy of stress myocardial perfusion MRI for detecting significant coronary artery disease (CAD). Free‐breathing, whole‐heart coronary MR angiography (MRA) was recently introduced as a method that can provide visualization of all three major coronary arteries within a single three‐dimensional (3D) acquisition. With further improvements in MRI techniques and the establishment of a standardized study protocol, cardiac MRI will play a pivotal role in managing patients with ischemic heart disease. J. Magn. Reson. Imaging 2007;26:3–13. © 2007 Wiley‐Liss, Inc.
Optically mediated nerve stimulation: Identification of injury thresholds
Authors: Wells Jonathon D. , Thomsen Sharon , Whitaker Peter , Jansen E. Duco , Kao Chris C. , Konrad Peter E. , Mahadevan‐Jansen Anita
Published: July 2007

Background and Objective

Transient optical nerve stimulation is a promising new non‐contact, spatially precise, artifact‐free neural excitation technique useful in research and clinical settings. This study evaluates safety of this pulsed infrared laser technique by histopathologic examination of stimulated peripheral nerves.

Study Design/Materials and Methods

Exposed rat sciatic nerves were functionally stimulated with the pulsed Holmium:YAG laser, previously validated as an effective tool for optical stimulation. Nerves were removed immediately and up to 2 weeks after stimulation and assessed histologically for thermal damage. Laser parameters studied include upper limits for radiant exposure, repetition rate, and duration of stimulation.

Results

Radiant exposures with <1% probability of thermal tissue damage (0.66–0.70 J/cm2) are significantly greater than radiant exposures required for reliable stimulation (0.34–0.48 J/cm2). The upper limit for safe laser stimulation repetition rate occurs near 5 Hz. Maximum duration for constant low repetition rate stimulation (2 Hz) is ∼4 minutes with adequate tissue hydration.

Conclusion

Results confirm that optical stimulation has the potential to become a powerful non‐contact clinical and research tool for brief nerve stimulation with low risk of nerve thermal damage. Lasers Surg. Med. 39:513–526, 2007. © 2007 Wiley‐Liss, Inc.
Clinical and positron emission tomography findings of chorea associated with primary antiphospholipid antibody syndrome
Authors: Wu Steve W. , Graham Brent , Gelfand Michael J. , Gruppo Ralph E. , Dinopolous Argirios , Gilbert Donald L.
Published: July 2007

A fourteen‐year‐old right‐handed male with a history of attention deficit hyperactivity disorder (ADHD) presented with alternating hemichorea. Laboratory findings included elevated anticardiolipin IgG and anti‐β2‐glycoprotein I IgG, which were consistent with primary antiphospholipid antibody syndrome. Positron emission tomography (PET) imaging revealed altered striatal metabolism in his left putamen while he was exhibiting right‐sided hemichorea. His symptoms resolved on prednisone; however, his antiphospholipid antibody profile remained markedly abnormal despite being symptom‐free for 26 months. © 2007 Movement Disorder Society
Noninvasive measurement of arterial cerebral blood volume using look‐locker EPI and arterial spin labeling
Authors: Brookes M.J. , Morris P.G. , Gowland P.A. , Francis S.T.
Published: July 2007

This paper describes a method of noninvasively measuring regional arterial cerebral blood volume fractions (CBVa) in vivo using the combination of Look‐Locker echo‐planar imaging (LL‐EPI) with arterial spin labeling (ASL). Using this technique the arterial inflow curve is rapidly sampled and the regional CBVa is measured, while tissue perfusion signals are suppressed. Two methods of spin labeling (LL‐EPI flow‐sensitive alternating inversion recovery (LL‐EPI‐FAIR) and LL‐EPI signal targeting using alternating radiofrequency (LL‐EPI‐STAR)) are assessed and their advantages discussed. The application of vascular crushing to LL‐EPI‐FAIR is described and used to validate the insensitivity of the sequence to the perfusion difference signal. LL‐EPI‐STAR is used to assess changes in CBVa in response to a finger‐tapping task. LL‐EPI‐STAR signal difference curves are shown to have a shortened vascular transit delay and increased peak signal change on activation. A 33 ± 14% increase in CBVa on activation is found. CBVa is measured with a 6‐s temporal resolution and the temporal response is compared with the BOLD signal change. CBVa is shown to increase more rapidly and return to baseline significantly faster than the BOLD signal change, which supports the suggestion that a change in CBVa is an input to the BOLD response. Magn Reson Med 58:41–54, 2007. © 2007 Wiley‐Liss, Inc.