bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Approach towards 2,3,5‐Trisubstituted Thiophenes via tandem Michael addition/intramolecular Knoevenagel condensation
Authors: Obrecht Daniel , Gerber Fernand , Sprengeir Daniel , Masquelin Thierry 
Published: December 2004

AbstractStarting from the easily available, highly functionalized acetylenic ketories 4a–i (Scheme 1), novel 2,3,5‐trisubstituted thiophenes 1a–i (Scheme 2) were synthesized in good yields using a tandem Michael‐addition/intramolecular Knoevenagel‐condensation strategy, featuring Cs2CO3/MgSO4 (1:2) as an efficient base to effect the cyclization. Subsequent simple one‐step transformations yielded 2,3‐disubstituted thiophene‐5‐carbaidehydes 7a–c, carboxylic‐acid derivatives 8, 9, and 11, and alcohol 10 (Scheme 3). These molecules constitute interesting novel thiophene‐containing building blocks, useful for the preparation of low‐molecular‐weight compound libraries by combinatorial and parallel‐chemistry techniques.
Solid‐Phase Total Synthesis of Cyclosporine Analogues
Authors: Ko Soo Y. , Wenger Roland M. 
Published: December 2004

AbstractSyntheses of cyclosporine analogues are reported wherein the peptide couplings were achieved in solid phase. The Wang resin was used as the solid support, and the peptide couplings commenced with the residue 11 of the cyclosporine skeleton. The couplings proceeded in a stepwide manner up to the residue MeBmt1, using symmetric anhydrides. The peptides were then cleaved off the resin, and the cyclization was achieved in solution using Castro's reagent. The solid‐phase synthesis described herein offers a very efficient method for the rapid synthesis of structurally diverse cyclosporine analogues in small quantities. The biological activities of the synthetic cyclosporine analogues were evaluated in two in vitro assays, including the IL‐2 reporter gene assay and the cyclophilin binding assay. The structure‐activity relationship is discussed.
Metal Complexes with Macrocyclic Ligands. PartXLV Axial coordination tendency in reinforced tetraazamacrocyclic complexes
Authors: Kowallick Ralph , Neuburger Markus , Zehnder Magareta , Kaden Thomas A. 
Published: December 2004

AbstractThe Cu2+ and Ni2+ complexes of three reinforced tetraazamacrocycles, containing a piperazine subunit and one or two alkyl substituents at the other two N‐atoms have been prepared and their structural properties studied. In solution, the Ni2+ complexes are square‐planar and show no tendency to axially coordinate a solvent molecule or an N ion. In contrast, the Cu2+ complexes change their geometry depending upon the donor properties of the solvent, being square‐planar in MeNO2 and pentacoordinate in DMF. They also easily react in aqueous solution with N to give ternary species with pentacoordinate geometry, the stabilities of which have been determined. In the solid state, the X‐ray crystal structures of three Cu2+ complexes also show both geometrical arrangements, two having a square‐planar, the other one a distorted square pyramidal geometry. The difference behavior of Ni2+ and Cu2+ stems from the fact that the structural change from square‐planar to square‐pyramidal can easily be accomplished for Cu2+, whereas, for Ni2+, it is accompanied by an electronic rearrangement from the low‐spin to the high‐spin configuration. The relatively rigid ligands cannot Adapt to the somewhat larger high‐spin Ni2+ion.
1,3‐Dipolare Cycloadditionen eines Carbonyl‐ylids mit 1,3‐Thiazol‐5(4H)‐thionen und Thioketonen
Authors: Meier Karl‐Richard , Linden Anthony , Heimgartner Heinz , Mlostoń Grzegorz 
Published: December 2004

1,3‐Dipolar Cycloadditions of a Carhonyl‐ylide with 1,3‐Thiazole‐5(4H)‐thiones and ThioketonesInp‐xylene at 150°, 3‐phenyloxirane‐2,2‐dicarbonitrile (4b) and 2‐phenyl‐3‐thia‐1‐azaspiro[4.4]non‐1‐ene‐4‐thione (1a) gave the three 1:1 adduets trans‐3a, cis‐3a, and 13ain 61, 21, and 3% yield, respectively (Scheme 3). The stereoisomers trans‐3a and cis‐3a are the products of a regioselective 1,3‐dipolar cycloaddition of carbonylylide 2b, generated thermally by an electrocyclic ring opening of 4b (Scheme 6), and the CS group of 1a. Surprisingly, 13a proved not to be a regioisomeric cycloadduct of 1a and 2b, but an isomer formed via cleavage of the OC(3) bond of the oxirane 4b. A reaction mechanism rationalizing the formation of 13a is proposed in Scheme 6. Analogous results were obtained from the reaction of 4b and 4,4‐dimethyl‐2‐phenyl‐1,3‐thiazole‐5 (4H)‐thione (1b, Scheme 3). The thermolysis of 4b in p‐xylene at 130° in the presence of adamantine–thione (10) led to two isomeric 1:1 adducts 15 and 16 in a ratio of ca. 2:1, however, in low yield (Scheme 4). Most likely the products are again formed viathe two competing reaction mechanisms depicted in Scheme 6. The analogous reactions of 4b with 2,2,4,4‐tetramethylcyclobutane‐1,3‐thione (11) and 9H‐xanthene‐9‐thione (12) yielded a single 1:1 adduct in each case (Schemes). In the former case, spirocyclic 1,3‐oxathiolane 17, the product of the 1,3‐dipolar cycloaddition with 2a corresponding to 3a, was isolated in only 11 % yield. It is remarkable that no 2:1 adduct was formed even in the presence of an excess of 4b. In contrast, 4b and 12 reacted smoothly to give 18 in 81 % yield; no cycloadduct of the carbonylylide 2a could be detected. The structures of cis‐3a, 13a, 15, and 18, as well as the structure of 14, which is a derivative of trans‐3a, have been established by X‐ray crystallography (Figs. 1–3, Table).
Non‐destructive Removal of the Bornanesultam Auxiliary in α‐Substituted N‐Acylbornane‐10,2‐sultanis under Mild Conditions: An efficient synthesis of enantiomerically pure ketones and aldehydes
Authors: Oppolzer Wolfgang , Darcel Christophe , Rochet Patrick , Rosset Stephane , De Brabander Jef 
Published: December 2004

Abstractα‐Substituted N‐acylbornane‐10, 2‐sultams 6, 9, and 10 can be converted into enantiomerically pure ketones 5. 13, and 14, respectively, via a two‐step procedure involving a known mercaptolysis reaction followed by an [Fe(acac)3]‐mediated coupling of the resulting S‐benzyl thioesters with Grignard reagents. Furthermore, enantiomerically pure aldehydes 23 can be obtained from α‐substituted N‐acylbornane‐10,2‐sultams 6 via a one‐step reduction with (i‐Bu)2AIH. No epimerization at the α‐chiral center is observed during the cleavage reaction whereby the chiral auxiliary, bornane‐10,2‐sultam 1 or ent‐l, was recovered. By using this methodology, several natural products or precursors thereof can be prepared.
Breakdown of Chlorophyll: Partial synthesis of a putative intermediary catabolite. Preliminary communication
Authors: Kräutler Bernhard , Mühlecker Walter , Anderl Maximilian , Gerlach Benjamin 
Published: December 2004

AbstractThe partial synthesis of 10,22‐dihydro‐4,5‐dioxo‐4,5‐secopheophorbide a (1) from pheophorbide a methyl ester (2) is described. A regioselective, photooxygenolytic reaction of (pheophorbidato a methyl ester)cadmium(II)(3) provides the entry to the crucial 4,5‐secoporphinoid structure in form of the (10,22‐dihydro‐4,5‐dioxo‐4,5‐seco‐pheophorbidato a methyl ester)cadmium(II) (4). The hydride reduction of this 4,5‐dioxo‐4,5‐secophytoporphyrin ester occurs selectively at the ‘eastern’ meso‐position to lead (after demetallation) to 10,22‐dihydro‐4,5‐dioxo‐4,5‐secopheophorbide a methyl ester (5). This oxobilin‐carbaldehyde has the structure assigned earlier to an ester of an isolation form of the red pigment(s) from Chlorella protothecoides. Hydrolysis of the propanoate ester function of 5, selectively catalyzed by pig liver esterase, then yields the title compound 1. The red tetrapyrrole 1 may represent an intermediary chlorophyll catabolite in degreening plants.
Synthesis of Benzo[a]heptalene
Authors: Guspanová Jana , Knecht Roger , Laganà Markus , Weymuth Christophe , Hansen Hans‐Jürgen 
Published: December 2004

AbstractBenzo[a]heptalene has been synthesized by two different approaches. The first one follows a pathway to hexahydrobenzo[a]heptalenone 19a that has been already described by Wenkert and Kim(Scheme). Indeed, 19a was obtained in a mixture with its double‐bond‐shifted isomer 19b. Reduction of this mixture to the corresponding secondary alcohols 26a/26b and elimination of H2O lead to a mixture of the tetrahydrobenzo[a]heptalenes 23a‐d (Scheme7 and 8). Reaction of 23a‐d with 2 equiv. of triphenylmethylium tetrafluoroborate in boiling CHCl3, followed by treatment with Me3N in CH2Cl2, generated directly 2, unfortunately in a mixture with Ph3CH that could not be separated from 2 (Scheme 10 and 11). The second approach via dimethyl benzo[a]heptalene‐6,7‐dicarboxylate (30) (Scheme 12) that was gradually transformed into the corresponding carbaldehydes 37 and 43 (Scheme 14) both of which, on treatment with the Wilkinson catalyst [RhCl(PPh3)3] at 130° in toluene, smoothly decarbonylated, finally gave pure 2 as an unstable orange, viscous oil. UV/VIS, NMR, and mass spectra of 2 are discussed in detail (cf. Chapt.3).
Solid‐Phase Synthesis of a Sialyl‐Tn‐Glycoundecapeptide of the MUC1 Repeating Unit
Authors: Liebe Beate , Kunz Horst 
Published: December 2004

AbstractThe synthesis of glycopeptides carrying tumour‐associated antigens is of interest for cancer diagnosis and treatment. Here, a very efficient route lo disaccharide threonine building block 8 is presented which allows the introduction of the sialyl‐Tn antigen into a peptide. The syntheses of the undecapeptide and the sialyl‐Tn‐containing glycoundecapeptide, which are a part of the repeating unit of MUC1, were performed by solid‐phase synthesis with an allylic anchor cleavable under neutral conditions. After detachment from the resin, the peptide and the glycopeptide arc completely deprotected giving the target compounds 13 and 15, respectively.
Synthesis and Properties of First and Second Generation Chiral Dendrimers with Triply Branched Units: A Spectacular Case of Diastereoselectivity
Authors: Murer Peter K. , Lapierre Jean‐Marc , Greiveldinger Guy , Seebach Dieter 
Published: December 2004

AbstractChiral triols (which may be considered as derivatives of tris(hydroxymethyl)methane), without (3‐5) and with aliphatic (6) or aromatic (7) elongating units, and the 1st‐ and 2nd‐generation benzylic branched bromides, 17, 18, 23, 24, 29, and 30 are subjected to Williamson etherification conditions (NaH in THF). This gave the first ‘fully chiral’ dendrimers, with triple branching and with a stereogenic center at each and every branching point (including the central building block: see 33‐42, 44, and 46‐49). Higher than 2nd‐generation dendrimers of this type could not be prepared. Certain combinations of diastereoisomeric 2nd‐generation branched bromides, 23, 24, 29, and 30, and enantiomeric center‐piece triols, 3 and 4, would smoothly react to give the desired dendrimers (e.g., 44, and 46‐49) and others would not, with the reactions stopping at the dendritic alcohols containing only two branches (e.g., 45, and 50‐53; see Schemes 4 and 5). Considering the distance at which the intermediate diastereoisomeric ‘doubly coupled’ dendritic alcohols differ in their configuration, this diastereodifferentiation or molecular recognition phenomenon (discovered by trying to prepare only 8 out of 239 possible diastereoisomers!) is a most surprising result. All compounds were fully characterized, and the 2nd‐generation dendrimers, e.g., 38, 40, and 47 with and without elongation were shown to be monodisperse and without defects, by MALDI‐TOF mass spectroscopy (cf. Fig. 4). A simple, unambiguous nomenclature for identification of the novel dendritic compounds is proposed and applied in the Exper. Part.
Conformation and Dynamics of (−)‐β‐Caryophyllene
Authors: Hübner Matthias , Rissom Beate , Fitjer Lutz 
Published: December 2004

Abstract(−)‐β‐Caryophyllene (1) adopts three conformations in solution: αα(48%), βα(28%), and ββ(24%). The conformations were identified by an analysis of the 13C‐ and 1H‐NMR spectra at −87.2 and −153.8° in connection with APT, HETCOR, and COSY spectra, and subsequent NOESY experiments. The activation parameters of the conversion αα → βα were determined from a bandshape analysis of exchange‐broadened 13C‐NMR spectra of 8‐[methylene‐13C]‐1 to give ΔH≠ = 5.9 ± 0.3 kcal/mol, ΔS = −8.1 ± 1.8 cal/mol. · K. and ΔG = −8.3 ± 0.8 kcal/mol. The observed population ratio of the different conformers is best described by MM3.
Dendritic styryl TADDOLs as novel polymer cross‐linkers: First application in an enantioselective Et2Zn addition mediated by a polymer‐incorporated titanate. Preliminary communication
Authors: Rheiner P. Beat , Sellner Holger , Seebach Dieter 
Published: December 2004

AbstractTADDOLs (α,α,α′,α′,‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanols) with dendritic branches attached to the aryl groups and with 8 or 16 peripheral styryl double bonds have been synthesized (4 and 5). With these compounds, dendritic molecules were employed for the first time as cross‐linkers in a polymerization. The resulting polystyrene was loaded with titanate (Ti(OCHMe2)4) to generate polymer beads incorporating Ti‐TADDOLate centers (Figs. 1 and 2) for enantioselective catalysis (Et2Zn addition to PhCHO). Compared with conventionally polymer‐attached, insoluble Ti‐TADDOLates (cf. 3), the new materials have a much higher catalytic activity, rather close to that of soluble analogs (Fig. 3).
Novel leptomycins from a streptomyces strain A92‐308902: Inhibitors of the Nucleo‐cytoplasmic translocation of the HIV‐1 regulatory protein Rev
Authors: Wang Ying , Ponelle Monique , Sanglier Jean‐Jacques , Wolff Barbara 
Published: December 2004

AbstractAs one of the regulatory gene products in the HIV‐1 genome, Rev protein must be translocated from the nucleus to the cytoplasm to exert its function. Therefore, inhibition of Rev protein translocation could be a useful target for HIV therapy. An extract from the Streptomyces strain A92‐308902 with very potent inhibitory activity was found in the course of a high throughput screening with a Rev translocation assay (RTA). Bioassay‐guided fractionation with gel filtration, normal‐phase and reversed‐phase chromatography yielded six RTA‐active metabolites belonging to the leptomycin family, the known leptomycin A (1), leptomycin B (2), kazusamycin B (3), and kazusamycin A (4). and the hitherto unknown dilactonmycin (5) and delactonmycin (6), together with an inactive cyclic hexadepsipeptide L‐156,620 (7). The structures were established mainly by spectroscopic methods (UV, FT‐IR, FAB‐MS, 1H‐NMR, 13C‐NMR(JMOD), DQ‐COSY, ROESY, HSQC, and HMBC). The configuration of all CC bonds of 1–6 was unambiguously established by analysis of coupling constants and ROESY spectra. All isolated leptomycins 1–6 inhibit Rev translocation at nanomolar concentrations. Six derivatives (2a–c and 4a–c) of leptomycin B (2) and kazusamycin A (4) were also prepared and tested in the RTA for preliminary investigations on structure‐activity relationships.
Structure and reactivity of a sulfoximine‐stabilized chiral dilithiocarbanion
Authors: Müller Jürgen F. K. , Neuburger Markus , Zehnder Margareta 
Published: December 2004

AbstractThe synthesis and X‐ray analysis of a racemic dilithiated S‐ethyl‐N‐methyl‐S‐phenylsulfoximine cluster 2 with N,N,N′,N′‐tetramethylethane‐1,2‐diamine (TMEDA) as coordinating solvent is presented. The lithium complex 2 consists of a mixed tetrameric mono‐ and dilithio salt. Unexpectedly, a separation of the enantiomers in mono‐and dilithiated antipodes with respect to the chirality center on the S‐atom is observed. Dilithiation of S‐ethyl‐N‐methyl‐S‐phenylsulfoximine (1) affords a chiral dinucleophile which undergoes highly regie‐ and stereoselective alkylation reactions with bis‐electrophiles.
Synthesis and structure of (carboxymethyl)‐functionalized cyclobuta‐fused uracil dimers
Authors: Carell Thomas , Epple Robert , Gramlich Volker 
Published: December 2004

AbstractHerein, we report a convenient method for the preparation of four benzyl‐ester‐protected, (carboxymethyl)‐functionalized cyclobuta‐fused uracil dimers 1–4, including the desired cis‐cisoid‐cis,syn‐ configured isomer 1, a compound which is suitable for the preparation of catalytic antibodies, synthetic receptors, and model compounds, required for the investigation of the DNA‐lesion, recognition step and DNA‐repair mechanisms. A comprehensive structure determination of each isomer by 1H‐NMR, and in the case of the cis‐cisoid‐cis,syn‐ and the cis‐traftsoid‐cis,Syn‐dimers by X‐ray crystal‐structure analysis, is also provided.
Ein erstes Beispiel eines porphyrinoiden Fulvalens: Synthese, Struktur, ESR‐ und elektrochemische Untersuchungen
Authors: Markl Gottfried , Hafner Markus , Kreitmeier Peter , Stadler Christian , Daub Jörg , Nöth Heinrich , Schmidt Martin , Gescheidt Georg 
Published: December 2004

AbstractA First Example of a Porphyrinoid Fulvalene: Synthesis, Structure, ESR and Electrochemical InvestigationsThe macrocyclic tetraepoxy‐1H‐[21]annulen‐1‐one 4 can by synthesized by the cyclizing Wittig reaction of 5,5′‐carbonylbis[furan‐2‐carboxaldehyde] (11) and the bisphosphonium salt 12, obtained from 2,2′‐bifuran‐5,5′‐dicarboxaldehyde (13). According to an X‐ray structure analysis, the annulenone 4 is not planar in the crystal; the 1H‐NMR spectra of 4 reveal an averaged planarity with respect to the NMR timescale. The McMurry reaction of 4 yields fulvalene 3 in 43% yield as the most expanded fulvalene hithertoo known. The X‐ray structure analyses of 3 surprising establishes a ‘syn’‐orientation of the two rings with respect to the central CC bond, thus forming a basket‐like molecule. The 1H‐NMR spectrum confirms the averaged planarity of both macrocycles in 3. CV and spectroelectrochemical measurements of 3 suggest a reversible two‐electron reduction producing dianion 15 with two aromatic, anionic 5a,15a‐didehydro‐10H‐21,22,23,24‐tetraoxa‐5a,15a‐dihomocorrole (= tetraoxa[22]porphyrin(2.1.2.0)) ring systems containing 22π electrons each. The formation of 15 can also be achieved chemically by reaction of 3 with metallic potassium. The dication 16 of 3 may be antiaromatic, but the exact electronic structure is dubious. ESR and ENDOR investigations on the radical cation and the radical anion of 3 indicate that the free electron is delocalized in the entire molecule.
Enantioselective 1,4‐Addition of Aliphatic Grignard Reagents to Enones Catalyzed by Readily Available Copper(I) thiolates derived from TADDOL. Preliminary communication
Authors: Seebach Dieter , Jaeschke Georg , Pichota Arkadius , Audergon Laurent 
Published: December 2004

AbstractTwo simple thiols derived from the parent TADDOL, α,α,α′,α′ tetraphenyl‐2,2‐dimethyl‐1,3‐clioxolan‐4,5‐dimethanol, are used to prepare Cu1 complexes C and D to catalyze (0.05 equiv.) 1,4‐additions of Grignard reagents RMgCl to cyclic enones with enantioselectivities which are comparable to or better than previously reported (enantiomer ratios up to 92:8).
Preparation and Absolute Configuration of (−)‐(E)‐α‐trans‐Bergamotenone
Authors: Chapuis Christian , Barthe Michel , Muller Bernard L. , Schulte‐Elte Karl H. 
Published: December 2004

AbstractThe synthesis, absolute configuration, and olfactive evaluation of (−)‐(E)‐α‐trans‐bergamotenone (= (−)‐(1′S,6′R,E)‐5‐(2′,6′‐dimethylbicyclo[3.1.1]hept‐2′‐en‐6′‐yl)pent‐3‐en‐2‐one; (−)‐1), as well as its homologue (−)‐19 are reperted. The previously arbitrarily attributed absolute configuration of 1 and of (−)‐α‐trans‐bergamotene (= (−)‐(1 S,6R)‐2,6‐dimethyl‐6‐(4‐methylpent‐3‐enyl)bicyclo[3.1. 1]hept‐2‐ene; (−)‐2), together with those of the structurally related aldehydes (−)‐3a,b and alcohols (−)‐4a,b, have been rigorously assigned.
Asymmetric Synthesis of (S)‐5,5,5,5′,5′,5′,5′‐Hexafluoroleucine
Authors: Zhang Cong , Ludin Christian , Eberle Marcel K. , Stoeckli‐Evans Helen , Keese Reinhart 
Published: December 2004

Abstract(S)‐5,5,5,5′,5′,5′‐Hexafluoroleucine ((S)‐13) of 81 % ee is prepared from hexafluoroacetone (l) and ethyl bromopyruvate (= ethyl 2‐oxopropanoate) in 7 steps with an overall yield of 18% (Schemes 1 and 2). Key step in this sequence is the highly enantioselective reduction of the carbonyl group in α‐keto ester 4 either by bakers' yeast (91 % ee) or by ‘catecholborane’ 6 utilizing an oxazaborolidine catalyst, yielding hydroxy ester (R)‐5 with 99% ee. The absolute configuration was determined by X‐ray analysis of the HCl adduct (S,R)‐9b of (2S)‐N‐[(R)‐ l‐phenylethyl]‐5,5,5,5′,5′,5′‐hexafluoroleucine ethyl ester.
7‐Deazapurine Oligodeoxyribonucleotides: The effects of 7‐deaza‐8‐methylguanine on dna structure and stability
Authors: Seela Frank , Chen Yaoming , Mittelbach Cathrin 
Published: December 2004

AbstractOligodeoxyribonucleotides containing 7‐deaza‐2′‐deoxy‐8‐methylguanosine (m8c7Gd; 2b) were prepared. For this purpose, the phosphonate 3a and the phosphoramidite 3b were synthesized and employed in solidphase oligodeoxyribonucleotide synthesis. The structures and the thermodynamic data of duplex formation of oligodeoxyribonucleotides containing 2b were investigated by temperature‐dependent CD and UV spectra and compared with those containing 7‐deaza‐2′‐deoxy‐7‐methylguanosine (m7c7Gd) or 7‐deaza‐2′‐deoxy‐guanosine (c7Gd; 2a). In general, compound 2b reduces the duplex stability. In case of the sequence d(m8c7G‐C)4 (18), the B → Z transition was facilitated by the incorporation of 2b. Moreover, a single 7‐deaza‐8‐methylguanine residue present in an oligodeoxyribonucleotide tract of guanine residues destabilizes the dG quadruplex significantly. This destabilization is more pronounced than in the case of 7‐deazaguanine or 7‐deaza‐7‐methyl‐guanine.
Synthesis and Study of New β‐Cyclodextrin ‘Dimers’ Having a Metal Coordination Center and carboxamide or urea linkers
Authors: Sallas Florence , Marsura Alain , Petot Virginie , Pintér István , Kovács Joseph , Jicsinszky Laszlo 
Published: December 2004

AbstractThe synthesis of new ‘bridged’ β‐cyclodextrin (β‐CD) ‘dimers’ 7–12 was successfully achieved by two one‐pot reactions from β‐CD (3) and 6A‐azido‐6A‐deoxy‐β‐CD (4). The ‘phosphine imine’ reaction was shown to be a superior approach compared to the Mitsunobu reaction as coupling strategy for the preparation of these ‘dimers’. NMR Data, along with molecular‐modelling calculations, suggest a ‘helical‐like’ arrangement for the phenanthroline‐diyl‐linked ‘dimer’ derivative 9. Complexation properties of 9 were established by UV‐VIS‐spectrophotometric titration toward four metals. Among them CuII or EuIII ions were complexed selectively by 9, but no complexation occurred with LaIII and ZnII. In addition a specific and interesting esterase activity toward the phosphodiester bond of bis(4‐nitrophenyl) phosphate anion was found in the case of the CuII complex of 9.
A Novel Solution‐ and Solid‐Phase Approach to 2,4,5‐tri‐ and 2,4,5,6‐tetrasubstituted pyrimidines and their conversion into condensed heterocycles
Authors: Masquelin Thierry , Sprenger Daniel , Baer Roman , Gerber Fernand , Mercadal Yves 
Published: December 2004

AbstractA novel general synthesis of 2,4,5‐tri‐ and 2,4,5,6‐tetrasubstituted pyrimidines 5a–d and 7a, e, f, g by condensation of thiouronium salts of type 3 with (ethoxymethylidene)malononitrile (4) and [bis(methylthio)methylidene]malononitrile (6), respectively, was first established in solution (Scheme 1) and successfully transferred onto solid support by using the polymer‐bound thiouronium salt 11 (Scheme 3). Further investigations were directed toward a multidirectional cleavage procedure of the 2‐(alkylsulfinyl) intermediates, obtained from the 2‐(alkylthio)pyrimidines 7a (Scheme 2) or 12 and 14 (Schemes 3 and 4), with different nucleophiles to form highly substituted pyrimidines. In addition, fused‐heterocycle derivatives 22a‐‐h, 24a–c, and 26a–e were generated in good‐to‐excellent yields by condensation of 7a, e, h with versatile isocyanates and isothiocyanates, with subsequent alkylation (Scheme 5).