Building photoswitchable 3,4'-AMPB peptides: Probing chemical ligation methods with reducible azobenzene thioesters

• Gehad Zeyat and
• Karola Rück-Braun

Beilstein J. Org. Chem. 2012, 8, 890–896, doi:10.3762/bjoc.8.101

• we had to place the ligation junction next to the third amino acid serine of the SKV binding motif. In the case of the conventional NCL, we used cysteine at the ligation site, and for the auxiliary mediated ligations, we decided to introduce auxiliary-glycine-conjugates at the N-terminus, due to the

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• ]. EPO consists of 166 amino-acid residues with four glycosylation sites, one O-glycosylation site positioned at serine 126 and three N-glycosylation sites positioned at aspargines 24, 38 and 83. EPO has been found to contain multiple glycoforms and the efficacy of EPO is heavily dependent on the type

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

Mutational analysis of a phenazine biosynthetic gene cluster in Streptomyces anulatus 9663

• Orwah Saleh,
• Katrin Flinspach,
• Lucia Westrich,
• Andreas Kulik,
• Bertolt Gust,
• Hans-Peter Fiedler and
• Lutz Heide

Beilstein J. Org. Chem. 2012, 8, 501–513, doi:10.3762/bjoc.8.57

• or not they are involved in the biosynthesis of secondary metabolites. The gene orf1 (1002 bp) showed similarities to serine proteases, and orf2 (1029 bp) to aspartate-semialdehyde dehydrogenases. The gene orf3 (348 bp) showed homology to transcriptional modulators of the PemK-like protein family [19

Novel fatty acid methyl esters from the actinomycete Micromonospora aurantiaca

• Jeroen S. Dickschat,
• Hilke Bruns and
• Ramona Riclea

Beilstein J. Org. Chem. 2011, 7, 1697–1712, doi:10.3762/bjoc.7.200

• to a highly conserved serine residue of the ACP (Scheme 1A). The acetyl moiety is then taken over by a conserved cystein residue of the ketosynthase (KS) making the ACP in turn available for the uptake of an elongation unit, in most cases malonyl-CoA, which is again selected and transferred by the AT

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

• cyanobacterial modular biosyntheses. Anabaenopeptilide The anabaenopeptilide pathway in the strain Anabaena 90 was described soon after first reports about microcystin biosynthesis. Anabaenopeptilides 2 belong to the cyanopeptolin family of depsipeptides that were shown to inhibit different types of serine

• integrated formyl transferase domain in the initiation module and NAD-dependent halogenase. The formation of Ahp remains to be analyzed. Aeruginosin Aeruginosins are specific inhibitors of serine type proteases and produced by different genera of freshwater cyanobacteria. The strain Planktothrix agardhii

• multidrug resistance [59]. The patellamide gene cluster consists of seven genes, expression of which in E. coli leads to the production of the peptides [59]. Heterocyclization of serine, cysteine and threonine, respectively is catalyzed by the heterocyclase PatD [60]. In contrast to other heterocyclases

Highly efficient cyclosarin degradation mediated by a β-cyclodextrin derivative containing an oxime-derived substituent

• Michael Zengerle,
• Florian Brandhuber,
• Christian Schneider,
• Franz Worek,
• Georg Reiter and
• Stefan Kubik

Beilstein J. Org. Chem. 2011, 7, 1543–1554, doi:10.3762/bjoc.7.182

• the phosphonylation of this nucleophilic group, similar to the phosphonylation of the serine residue in the active site of AChE during OP-mediated inhibition of this enzyme. If the compound thus formed is hydrolytically unstable, it will be cleaved in the aqueous medium, releasing the original

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• D-xylulose (28) from D,L-serine (26) and D,L-glyceraldehyde (25) involving three enzymes in a single continuously stirred tank reactor (CSTR) was presented by Bongs (Scheme 9) [32]. Here, a D-amino acid oxidase was used to form hydroxypyruvic acid (27) from D-26, which was subsequently converted to

• resolution of (rac)-1-phenylethanol (22) in supercritical CO2 in a packed-bed reactor loaded with acidic zeolite (A) and Novozym 435 (E) [30]. Synthesis of D-xylulose (28) from D,L-serine (26) and D,L-glyceraldehyde (25) in a continuously operated enzyme membrane reactor. E1: D-Amino acid oxidase; E2

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• bearing an NH- or an OH-group. Negishi cross-coupling in the presence of a serine moiety. Radical catalysis for the performance of very fast Kumada reactions. MgCl2-mediated addition of functionalized aromatic, heteroaromatic, alkyl and benzylic organozincs to aldehydes, ketones and carbon dioxide

A novel high-yield synthesis of aminoacyl p-nitroanilines and aminoacyl 7-amino-4-methylcoumarins: Important synthons for the synthesis of chromogenic/fluorogenic protease substrates

• Xinghua Wu,
• Yu Chen,
• Herve Aloysius and
• Longqin Hu

Beilstein J. Org. Chem. 2011, 7, 1030–1035, doi:10.3762/bjoc.7.117

• since they are often the starting materials for the synthesis of chromogenic substrates for serine proteases. Due to the presence of the guanidino group, the synthesis of Nα-protected Arg-pNA was especially challenging. We used Boc-Arg-OH∙HCl directly without protecting the guanidino group and found

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

• María Martín-Rodríguez,
• Carmen Nájera,
• José M. Sansano,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2011, 7, 988–996, doi:10.3762/bjoc.7.111

• as NS2, NS3 (which bear serine proteinase, helicase, and NTPase activities), NS4A, NS4B, NS5A (regulators of RNA replication), and NS5B (the RNA-dependent RNA polymerase) are generated [2][3] and, in fact, constitute the main targets. At the moment, there are many drugs under clinical trial

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• broussonetines. For instance, the syntheses of broussonetines C, D, M, O and P were completed by Falomir, Marco et al. [62][63] in a convergent, stereocontrolled way starting from commercial D-serine (55) as the chiral precursor and by applying the critical step of cross-metathesis (the first-ever synthesis of

• (Scheme 12) [8]. Takahata et al. [64] exploited RCM for the contruction of the piperidine ring of 1-deoxynojirimycin (62) and its congeners (1-deoxymannonojirimycin (63), 1-deoxyaltronojirimycin (65), and 1-deoxyallonojirimycin (66), Scheme 13). In their methodology, the D-serine-derived Garner aldehyde

• et al. [72] based again on the Garner aldehyde 69 derived from D-serine. To construct the chiral 1,2,5,6-tetrahydropyridine core 125, the authors resorted to catalytic ring-closing metathesis induced by the 1st-generation Grubbs catalyst 2, with subsequent stereoselective dihydroxylation (under

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

• consequently slowing down the irreversible acetylation of a serine residue by aspirin itself. This finding is relevant as aspirin is clinically used in combination with celecoxib to attenuate its cardiovascular side effects. Based on this in vitro study, it is suggested that the cardioprotective effects of low

• a nearby phenylalanine residue, whilst the trifluoromethyl group interacts with serine and arginine residues in a lipophilic pocket (Figure 8) [83]. In the discovery chemistry route [84] the heterocycle core was prepared from a SNAr reaction between chloropyrazine (276) and excess hydrazine

Achiral bis-imine in combination with CoCl₂: A remarkable effect on enantioselectivity of lipase-mediated acetylation of racemic secondary alcohol

• K. Arunkumar,
• M. Appi Reddy,
• T. Sravan Kumar,
• B. Vijaya Kumar,
• K. B. Chandrasekhar,
• P. Rajender Kumar and
• Manojit Pal

Beilstein J. Org. Chem. 2010, 6, 1174–1179, doi:10.3762/bjoc.6.134

• ., serine, histidine, and aspartate) at the active site of CAL-B increases the nucleophilicity of the serine residue. This then interacts with the carbonyl group of the vinyl acetate to form the “acyl-enzyme intermediate” T-1 (Scheme 4) which finally transfers the acyl group to the substrate alcohol 4 via T

Hybrid biofunctional nanostructures as stimuli-responsive catalytic systems

• Gernot U. Marten,
• Thorsten Gelbrich and
• Annette M. Schmidt

Beilstein J. Org. Chem. 2010, 6, 922–931, doi:10.3762/bjoc.6.98

• , the immobilization of trypsin as a serine protease introduces biocatalytic activity. These components result in hybrid nanostructures, which serve as a recoverable reaction system that can be activated reversely by external ac magnetic fields, by using the thermal energy developed by magnetic heating

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

• antigen) linked to β3-homo-serine are known. Despite their importance as specific tumour antigens, conjugates of Fmoc-β3hSer and Fmoc-β3hThr carrying larger TACA structures such as the Thomsen–Friedenreich antigen (TF) or its sialylated variants (α2-6sTF and α2-3sTF) have not been reported to date. By

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

An enantiomerically pure siderophore type ligand for the diastereoselective 1 : 1 complexation of lanthanide(III) ions

• Markus Albrecht,
• Olga Osetska,
• Thomas Abel,
• Gebhard Haberhauer and
• Eva Ziegler

Beilstein J. Org. Chem. 2009, 5, No. 78, doi:10.3762/bjoc.5.78

• chelating moiety, which can form highly stable complexes with a series of first row transition metals. (ii) Chirality: The enterobactin-backbone is based on L-serine units and therefore is chiral (and enantiomerically pure). This chiral information gives all three ligand units the same spatial orientation

(−)-Complanine, an inflammatory substance of marine fireworm: a synthetic study

• Kazuhiko Nakamura,
• Yu Tachikawa and
• Daisuke Uemura

Beilstein J. Org. Chem. 2009, 5, No. 12, doi:10.3762/bjoc.5.12

• configuration (of the OH adjacent carbon atom) is R [4]. The similarity of the structures suggests a close relationship in their biosynthetic pathways. It can be hypothesized that complanine is biosynthesized from glycine, based on comparison with serine- or alanine-derived natural products [3][4][10][11]. The

Convenient method for preparing benzyl ethers and esters using 2-benzyloxypyridine

• Susana S. Lopez and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2008, 4, No. 44, doi:10.3762/bjoc.4.44

• trifluorotoluene, but toluene has a lower dipole moment and also is subject to Friedel–Crafts benzylation under the reaction conditions [6][22]. Trifluorotoluene (also known as benzotrifluoride or BTF) is recommended as a “green” solvent alternative to dichloromethane [23]. Benzylation reactions of N-Boc-serine 3d

• (entry 7, 84%) and methyl lactate (3e, 79%) verify compatibility with esters and carbamates. Note that the benzylation of N-Boc-serine methyl ester (3d) compares favourably to analogous reactions reported previously [24], because the neutral reaction conditions described herein are compatible with the

Synthesis of (S)-1-(2-chloroacetyl)pyrrolidine- 2-carbonitrile: A key intermediate for dipeptidyl peptidase IV inhibitors

• Santosh K. Singh,
• Narendra Manne and
• Manojit Pal

Beilstein J. Org. Chem. 2008, 4, No. 20, doi:10.3762/bjoc.4.20

• molecules [1][2][3]. DPP-IV, a member of the prolyl oligopeptidase family of serine protease, cleaves the N-terminal dipeptide from peptides with proline or alanine in the second position. As a result of intense pharmaceutical research, several DPP-IV inhibitors have been discovered and a few of them

Pd-catalysed [3 + 3] annelations in the stereoselective synthesis of indolizidines

• Olivier Y. Provoost,
• Andrew J. Hazelwood and
• Joseph P. A. Harrity

Beilstein J. Org. Chem. 2007, 3, No. 8, doi:10.1186/1860-5397-3-8

• modification of the route described by Righi and co-workers [11]. Accordingly, tosyl protection of (R)-serine 5 followed by esterification and TBDPS-protection provided 6 in good overall yield. Ester reduction was carried out conveniently on multigram scale using LiBH4 to give an amino alcohol that was