An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• -containing peptide: glycine–arginine–glycine–aspartic acid–serine–proline (GRGDSP) or EILDV. Neither peptide, up to 2 mM, completely inhibited adhesion of WM-115 cells to fibronectin. We then decided to combine the peptidic integrin ligands with GSF to see if an antagonism or additive effect upon cell

Thiophene-based donor–acceptor co-oligomers by copper-catalyzed 1,3-dipolar cycloaddition

• Stefanie Potratz,
• Amaresh Mishra and
• Peter Bäuerle

Beilstein J. Org. Chem. 2012, 8, 683–692, doi:10.3762/bjoc.8.76

• sulfate, 10 mol % sodium ascorbate, which reduces Cu(II) to Cu(I), 10 mol % sodium carbonate and 20 mol % L-proline as ligand were reacted in the solvent system DMSO–water at 60 °C. The co-oligomeric product 5 was obtained in only 10% yield (Table 1, entry 1). When the stabilizing ligand was changed to N

A concise synthesis of 3-(1-alkenyl)isoindolin-1-ones and 5-(1-alkenyl)pyrrol-2-ones by the intermolecular coupling reactions of N-acyliminium ions with unactivated olefins

• Nianhong Lu,
• Lihong Wang,
• Zhanshan Li and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 192–200, doi:10.3762/bjoc.8.21

• 1-alkenylboronic acid, or esters [23][24] besides allylsilane. For example, Angst reported the coupling of styrylsilanes with N-acyl-2-chloroglycine esters catalyzed by SnCl4 to give the 3-styryl glycine derivatives in 1987 [19]; Wistrand reported the coupling of methyl 1-acyl-5-methoxy-L-proline

• with 1-alkenylcoppers catalyzed by BF3·OEt2 to give methyl 1-acyl-5-(1-alkenyl)-L-proline in 1992 [20]; Menicagli reported the coupling of N-acylisoquinolium chloride with di-isobutyl 1-hexenylalanes to give 1,2-dihydro-2-acyl-1-hexenylisoquinolines in 2008 [22]; Schaus reported the coupling of 1

Continuous proline catalysis via leaching of solid proline

• Suzanne M. Opalka,
• Ashley R. Longstreet and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2011, 7, 1671–1679, doi:10.3762/bjoc.7.197

• homogeneous catalyst can be prepared continuously via reaction with a packed-bed of a catalyst precursor. Specifically, we perform continuous proline catalyzed α-aminoxylations using a packed-bed of L-proline. The system relies on a multistep sequence in which an aldehyde and thiourea additive are passed

• through a column of solid proline, presumably forming a soluble oxazolidinone intermediate. This transports a catalytic amount of proline from the packed-bed into the reactor coil for subsequent combination with a solution of nitrosobenzene, affording the desired optically active α-aminooxy alcohol after

• reduction. To our knowledge, this is the first example in which a homogeneous catalyst is produced continuously using a packed-bed. We predict that the method will not only be useful for other L-proline catalyzed reactions, but we also foresee that it could be used to produce other catalytic species in flow

Tertiary alcohol preferred: Hydroxylation of trans-3-methyl-L-proline with proline hydroxylases

• Christian Klein and
• Wolfgang Hüttel

Beilstein J. Org. Chem. 2011, 7, 1643–1647, doi:10.3762/bjoc.7.193

• of trans-3-methyl-L-proline with the α-ketoglutarate (α-KG) dependent oxygenases, cis-3-proline hydroxylase type II and cis-4-proline hydroxylase (cis-P3H_II and cis-P4H). With cis-P3H_II, the tertiary alcohol product (3R)-3-hydroxy-3-methyl-L-proline was obtained exclusively but in reduced yield (~7

• %) compared to the native substrate L-proline. For cis-P4H, a complete shift in regioselectivity from C-4 to C-3 was observed so that the same product as with cis-P3H_II was obtained. Moreover, the yields were at least as good as in control reactions with L-proline (~110% relative yield). This result

• stereospecific hydroxylation of trans-3-methyl-L-proline to (3R)-3-hydroxy-3-methyl-L-proline with two different proline hydroxylases. In contrast to the mechanistically related and more common prolyl hydroxylases, which accept peptide bound proline as a substrate and play a key role in collagen biosynthesis

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• neurotoxins produced by cyanobacteria. A gene cluster for the alkaloid was first described for the strain Oscillatoria sp. PCC 6506 [36]. Analysis of the gene cluster and feeding studies suggested a biosynthetic scheme starting from L-proline and involving three polyketide synthases, with (S)-1-pyrolline-5

• ) Formation of the guanidinoacetate starter unit for the subsequent PKS assembly line of cylindrospermopsin (4). D) Formation of the (S)-pyrroline-5-carboxylate starter unit from proline in anatoxin-a (6) synthesis. ACP: Acyl carrier protein. Structures of NRPS and PKS products in marine cyanobacteria. A

Continuous-flow enantioselective α-aminoxylation of aldehydes catalyzed by a polystyrene-immobilized hydroxyproline

• Xacobe C. Cambeiro,
• Rafael Martín-Rapún,
• Pedro O. Miranda,
• Sonia Sayalero,
• Esther Alza,
• Patricia Llanes and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2011, 7, 1486–1493, doi:10.3762/bjoc.7.172

• Franqués, 1. E-08028, Barcelona, Spain 10.3762/bjoc.7.172 Abstract The application of polystyrene-immobilized proline-based catalysts in packed-bed reactors for the continuous-flow, direct, enantioselective α-aminoxylation of aldehydes is described. The system allows the easy preparation of a series of β

• -immobilized catalysts; proline; Introduction Optically active α-hydroxycarbonyl moieties are highly versatile functional synthons and are present in a wide range of biologically active natural products [1][2]. Traditional strategies for the preparation of these kinds of synthons involves the oxidation of

• organocatalytic approaches to the direct enantioselective α-aminoxylation of carbonyl compounds and, shortly after, to the implementation of the α-aminoxylation of aldehydes with proline as catalyst [14][15] (Scheme 1). In 2004, the scope of the reaction was extended to ketones [16][17] and the reaction was

PEG-embedded KBr₃: A recyclable catalyst for multicomponent coupling reaction for the efficient synthesis of functionalized piperidines

• Sanny Verma,
• Suman L. Jain and
• Bir Sain

Beilstein J. Org. Chem. 2011, 7, 1334–1341, doi:10.3762/bjoc.7.157

• tetrabutylammonium tribromide (TBATB) [30], bromodimethylsulfonium bromide (BDMS) [31], InCl3 [32] and L-proline/TFA [33] were reported for the one-pot syntheses of these heterocyclic compounds. However, tedious synthetic procedures, the need for high catalyst loadings, and the expense and non-recyclability of the

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• attempts to incorporate proline-derived moieties failed. N-Benzylproline (41) turned out to be almost insoluble in ethereal solvents, which might explain why the desired β-ketoenamide was not formed [43]. To increase the solubility of the proline component, we changed the protective group from benzyl to

• the more lipophilic trityl group [44]. Surprisingly, the use of trityl-protected proline did not give the β-ketoenamide 47 as main product (Scheme 3). Instead, a diastereomeric 1:1 mixture of the β-keto-enolester 48 was isolated in 49% yield together with minor amounts of the expected product 47. The

• of β-ketoenamides 16. Reaction of proline derivative 45 and formation of β-ketoenamide 47 and enolester 48. Synthesis of pyrid-4-yl nonaflate 52. O-Methylation of pyridine derivatives 22 and 30 followed by desilylation. Formation of 5-alkoxypyrimidines from β-alkoxy-β-ketoenamides. Scope of the

Asymmetric synthesis of tertiary thiols and thioethers

• Jonathan Clayden and
• Paul MacLellan

Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68

• secondary thiol derivatives. These were prepared by diastereoselective electrophilic additions in proline-derived systems [71][72] and asymmetric alkylation of thiocarbamates in the presence of a chiral ligand [73][74]. Stereospecific functionalisation of configurationally stable lithiated thiocarbamates

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• chloride 89 are added concurrently from two different sides of the reactor to stop these reagents reacting with each other. This method of adding the reagents circumvents the necessity to isolate the magnesium salt of the indole and increases the yield from 50 to 82%. The carbonyl group of the proline side

Effects of anion complexation on the photoreactivity of bisureido- and bisthioureido-substituted dibenzobarrelene derivatives

• Heiko Ihmels and
• Jia Luo

Beilstein J. Org. Chem. 2011, 7, 278–289, doi:10.3762/bjoc.7.37

• dibenzobarrelene derivative 1c which forms the chiral ammonium carboxylate 1c-P with (S)-proline (Scheme 2). After irradiation, acidic workup and subsequent esterification with diazomethane, the dibenzosemibullvalene 2c was obtained with high enantiomeric excess (>95% ee) [35][36]. Interestingly, several

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• bromide affected the yield only marginally [63]. A second example of intramolecular coupling is the synthesis of promazine drugs (56) that are interesting due to their clinical use for psychotropic medication. The CuI/L-proline-catalysed cascade process, developed by Ma et al., gave the best yields when 2

• , reaction temperatures (90–115 °C) and reaction times (48 h) are comparable to the palladium-catalysed processes. Ligand-free and ligand-assisted reaction conditions have been applied in the synthesis of biologically active compounds. DMEDA, proline and phenanthroline are the most commonly used ligands. In

Surfactant catalyzed convenient and greener synthesis of tetrahydrobenzo[a]xanthene-11-ones at ambient temperature

• Pravin V. Shinde,
• Amol H. Kategaonkar,
• Bapurao B. Shingate and
• Murlidhar S. Shingare

Beilstein J. Org. Chem. 2011, 7, 53–58, doi:10.3762/bjoc.7.9

• , synthetic methods that involve tetra(n-butyl)ammonium fluoride (TBAF) [25] and proline triflate [26] in water have been described. However, the major problems associated with these routes are the need for higher/reflux conditions and longer reaction times. Therefore, it was thought worthwhile to develop a

Anthracene appended pyridinium amide–urea conjugate in selective fluorometric sensing of L-N-acetylvaline salt

• Kumaresh Ghosh,
• Tanmay Sarkar and
• Asoke P. Chattopadhyay

Beilstein J. Org. Chem. 2010, 6, 1211–1218, doi:10.3762/bjoc.6.139

• excited state of anthracene is regulated in different ways. We presume that receptor 1 may follow any equilibrium-binding mode A, B or C with valine, alanine and phenylglycine salts in solution as shown in Figure 5. This is also true for the mandelate, pyruvate and proline salts. Relevance of the

Synthesis of a novel analogue of DPP-4 inhibitor Alogliptin: Introduction of a spirocyclic moiety on the piperidine ring

• Arumugam Kodimuthali,
• Padala Lakshmi Prasunamba and
• Manojit Pal

Beilstein J. Org. Chem. 2010, 6, No. 71, doi:10.3762/bjoc.6.71

• dipeptidyl peptidase-4 (DPP-4; CD26; E.C. 3.4.14.5) by small molecules has emerged as one of the key approaches for the treatment of type-2 diabetes [1][2][3][4][5]. DPP-4, a member of the prolyl oligopeptidase family of serine protease, cleaves the N-terminal dipeptide from peptides with proline or alanine

Synthesis of glycosylated β³-homo-threonine conjugates for mucin-like glycopeptide antigen analogues

• Florian Karch and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2010, 6, No. 47, doi:10.3762/bjoc.6.47

• pseudo-glycopeptide was assembled in an automated synthesiser by the Fmoc-strategy on a TentaGel S resin 5 equipped with a bulky trityl linker [38] to avoid diketopiperazine formation and pre-loaded with Fmoc-proline (Scheme 2). The first 13 amino acids of the MUC1 sequence were coupled under standard

• -L-valyl-O-[α-3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-galactopyranosyl]-homo-β3-threonyl-L-seryl-L-alanyl-L-prolyl-L-aspartyl-L-threonyl-L-arginyl-L-prolyl-L-alanyl-L-prolyl-L-glycyl-L-seryl-L-threonyl-L-alanyl-L-proline 7: The synthesis was carried out in an Applied Biosystems ABI 433A peptide

• -L-alanyl-L-prolyl-L-glycyl-L-seryl-L-threonyl-L-alanyl-L-proline 8: Peptide 7 was dissolved in 10 mL of methanol (HPLC grade). A fresh solution of sodium methanolate in methanol (0.5 g Na in 25 mL methanol (HPLC grade)) was added drop wise until pH 9.5 was reached. The reaction mixture was stirred

The C–F bond as a conformational tool in organic and biological chemistry

• Luke Hunter

Beilstein J. Org. Chem. 2010, 6, No. 38, doi:10.3762/bjoc.6.38

• enantioselectivity suggesting that the fluorine atom of 35 helps to rigidify the activated intermediate and thereby enhances selectivity. Another fluorinated organocatalyst has recently featured in the first example of an asymmetric transannular aldol reaction (Figure 10) [35]. (S)-proline (39) is able to catalyse

• Cγ-exo proline ring shape, reinforced by the F–C–C–N gauche effect, could be partly responsible for the high enantioselectivity of catalyst 41. As an illustration of the importance of this work, catalyst 41 has already been put to good use in a total synthesis of the natural product (+)-hirsutine (46

• is often proline (39) and Yaa is often 4(R)-hydroxyproline (63). The triple helix is partly held together by backbone hydrogen bonds and for many years it was thought that the hydroxyl groups of the 4(R)-hydroxyproline residues (63) contributed to the stability of collagen by providing extra hydrogen

C-Arylation reactions catalyzed by CuO-nanoparticles under ligand free conditions

• Mazaahir Kidwai,
• Saurav Bhardwaj and
• Roona Poddar

Beilstein J. Org. Chem. 2010, 6, No. 35, doi:10.3762/bjoc.6.35

• of attention has been focused on the development of Pd catalyzed arylation [8][9][10][11]. Another important protocol involves arylation of activated methylene compounds mediated by copper salts [12][13]. Recently, proline has also been used along with CuI for C-arylation [14]. But some of the

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

Enantioselective synthesis of tricyclic amino acid derivatives based on a rigid 4-azatricyclo[5.2.1.0^2,6]decane skeleton

• Matthias Breuning,
• Tobias Häuser,
• Christian Mehler,
• Christian Däschlein,
• Carsten Strohmann,
• Andreas Oechsner and
• Holger Braunschweig

Beilstein J. Org. Chem. 2009, 5, No. 81, doi:10.3762/bjoc.5.81

• at a more remote position of the molecule, but still in close spatial proximity to the amino function. Examples are β-proline (4) [18][19], the bispidinium salt 5 [20], and the binaphthyl-derived amino acid 6 [21][22][23], which provided excellent enantioselectivities in several aldol and Mannich

Can we measure catalyst efficiency in asymmetric chemical reactions? A theoretical approach

• Shaimaa El-Fayyoumy,
• Matthew H. Todd and
• Christopher J. Richards

Beilstein J. Org. Chem. 2009, 5, No. 67, doi:10.3762/bjoc.5.67

• anecdotally refer to a “good“ or “bad“ reaction, there is no system for comparing those reactions with each other. Well-known examples of asymmetric catalysis such as the Sharpless asymmetric dihydroxylation, the Corey oxazaborolidine ketone reduction or the proline-catalysed aldol reaction are almost

• asymmetric hydrogenation, which gives a product of 79% ee, is employed in the industrial multi-tonne synthesis of (S)-metolachlor [3]. An instructive comparison may be made between an antibody capable of catalysing an intramolecular, asymmetric aldol reaction and proline, capable of catalysing the same

• reaction (the Hajos–Parrish–Eder–Sauer–Wiechert reaction – entries 8 and 9). Proline performs slightly better in this reaction, despite being used at a loading of 48 mol % (!) in one of the original reports, and this is partly due to the very large molecular weight of the antibody. It can be challenging to

A convenient method for preparing rigid-core ionic liquid crystals

• Julien Fouchet,
• Laurent Douce,
• Benoît Heinrich,
• Richard Welter and
• Alain Louati

Beilstein J. Org. Chem. 2009, 5, No. 51, doi:10.3762/bjoc.5.51

• sealed tube over 72 h to afford 1-[4-(dodecyloxy)phenyl]-1H-imidazole (A) in a good (<80%) and reproducible yield (Scheme 2). Swager has already published the synthesis of compound A under standard Ullman conditions (K2CO3, CuI, L-proline in DMSO, 16 h at 110 °C) [22]. The aryl-imidazole A was purified

2-Phenyl- tetrahydropyrimidine- 4(1H)-ones – cyclic benzaldehyde aminals as precursors for functionalised β²-amino acids

• Markus Nahrwold,
• Arvydas Stončius,
• Anna Penner,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2009, 5, No. 43, doi:10.3762/bjoc.5.43

• employed in peptide chemistry as asparagine protective groups [52] and as proline mimetics [40]. The class of compounds described in this paper can therefore be considered as a versatile tool in peptide and amino acid chemistry. X-ray crystal structure of 10 [44]. Comparison of coupling constants (C5–C6

Asymmetric synthesis of biaryl atropisomers by dynamic resolution on condensation of biaryl aldehydes with (−)-ephedrine or a proline- derived diamine

• Ann Bracegirdle,
• Jonathan Clayden and
• Lai Wah Lai

Beilstein J. Org. Chem. 2008, 4, No. 47, doi:10.3762/bjoc.4.47

• Ann Bracegirdle Jonathan Clayden Lai Wah Lai School of Chemistry, University of Manchester, Oxford Rd., Manchester M13 9PL, UK 10.3762/bjoc.4.47 Abstract Atropisomeric biaryl aldehydes undergo diastereoselective condensation with (−)-ephedrine and with a proline-derived diamine, with selectivity

• ] and ureas [18][19][20], we have explored the opportunities offered by dynamic kinetic [21][22][23] and dynamic thermodynamic [24] resolution [11][16][25][26][27][28][29][30]. We reported methods for the latter based on resolving “auxiliaries” which include silylethyl groups [28], proline-derived

• substrates Previous success with stereocontrol employing ephedrine-derived oxazolidines [15][26][27][34][35] and proline-derived imidazolidines [25][27] prompted us to investigate the thermal stability and conformational preferences of similar products arising from condensation reactions of 2-formylbiaryls