Synthesis of fluorescent (benzyloxycarbonylamino)(aryl)methylphosphonates

• Michał Górny vel Górniak,
• Anna Czernicka,
• Piotr Młynarz,
• Waldemar Balcerzak and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 741–745, doi:10.3762/bjoc.10.68

• acids and their short peptides are a class of well-established inhibitors of serine proteases [11][12]. Their mechanism of action involves phosphonylation of the active-site of these enzymes with simultaneous release of the appropriate phenol [13][14]. Therefore, the synthesis of such inhibitors

• carrying fluorescent probes in their side chains or in the ester phosphonate moieties might find an application in constructing fluorescent probes for studying structural requirements of enzymes having serine in their active sites (proteinases and phosphatases) or to study their elevated level in various

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• be conveniently obtained by loading coenzyme A (CoA) thioesters onto active site serine residues of recombinant ACPs by using 4'-phosphopantetheinyl transferases [12][14]. However, coenzyme A thioesters are synthetically hard to access, especially if the substrate structure is complex. Results and

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• and triazines, whereas azepines form an important class of seven-membered cyclic peptidomimetics. Four membered ring constraints β-Lactams The smallest class of cyclic peptidomimetics is that of the β-lactams. β-lactams are effective antibiotics [30] but also show inhibitory activities against serine

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• (commercial trade names Halocur® (lactate salt) and Stenorol® (hydrobromide salt)) [22]. Other relevant examples are 3-hydroxypipecolic acids, which serve as (conformationally restricted) substitutes of proline and serine [23][24] and have been incorporated into diverse bioactive peptidomimetics [25][26], and

A unified approach to the important protein kinase inhibitor balanol and a proposed analogue

• Tapan Saha,
• Ratnava Maitra and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2013, 9, 2910–2915, doi:10.3762/bjoc.9.327

• developed using an efficient fragment coupling protocol which proceeded in good overall yield. Keywords: azepane; balanol; Garner’s aldehyde; PKC inhibitor; ring-closing metathesis; Introduction Protein kinase C (PKC) is a family of phospholipid-dependent kinases that phosphorylate serine and threonine

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• deleterious epimerization of the existing stereocenter in Garner’s aldehyde. Keywords: asymmetric synthesis; Garner’s aldehyde; natural product synthesis; L-serine; Introduction “The universe is a dissymmetrical whole. I am inclined to think that life, as manifested to us, must be a function of the

• (formed in situ from the reaction of AcCl with MeOH) in MeOH [27]. The serine methyl ester hydrochloride salt was then protected with Boc anhydride. The N,O-acetal was formed using BF3·Et2O and DMP in acetone (Scheme 2). For the reduction they followed Garner’s procedure. This method allows an easy access

• reduction can be used. The ester can be reduced to alcohol 6 (e.g., with NaBH4/LiCl) and then oxidized to 1 with non-basic methods (e.g., IBX/DMP [30] or TEMPO/NaOCl [31] to name a few), which will not epimerize the α-center. For our synthesis of 1, we adopted a slightly modified sequence [32]. L-Serine (2

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• than 30 published syntheses up to now. Most frequently they are based on transformations of starting materials available from the ”chiral pool”, e.g. L-serine [7][8][9][10][11][12][13][14][15][16][17][18], or by asymmetric catalysis [19][20][21][22][23][24][25]. Several publications also focused on the

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• -protected analog [40][41]. We prepared aldehyde (S)/(R)-2 on a multigram scale in three steps starting from commercial available (S)/(R)-serine methylester hydrochloride by treatment with Cbz-Cl [42], acetalization with dimethoxypropane [43], and ester reduction with DIBAL-H [44]. In our hands, this pathway

• ) was carried out (Scheme 5). The aldehyde (R)-2, which was prepared from D-serine [42][43][44], underwent chelation-controlled nucleophilic addition of metallated alkyne 3 [45] to give the propargyl alcohol 14 in 84% yield and a syn-diastereoselectivity of >95:5 [7][46][47]. After tosylation of 14 (85

Synthesis of mucin-type O-glycan probes as aminopropyl glycosides

• David Benito-Alifonso,
• Rachel A. Jones,
• Anh-Tuan Tran,
• Hannah Woodward,
• Nichola Smith and
• M. Carmen Galan

Beilstein J. Org. Chem. 2013, 9, 1867–1872, doi:10.3762/bjoc.9.218

• -deoxy-D-galactose to serine or threonine. This saccharide forms the inner part of the characteristic core oligosaccharides from where glycans are extended through common core (di- and trisaccharide) structures, cores 1–8 [6][7][8]. The mucin-type oligosaccharides identified to date have remarkable

New tridecapeptides of the theonellapeptolide family from the Indonesian sponge Theonella swinhoei

• Annamaria Sinisi,
• Barbara Calcinai,
• Carlo Cerrano,
• Henny A. Dien,
• Angela Zampella,
• Claudio D’Amore,
• Barbara Renga,
• Stefano Fiorucci and
• Orazio Taglialatela-Scafati

Beilstein J. Org. Chem. 2013, 9, 1643–1651, doi:10.3762/bjoc.9.188

• oxazole or thiazole rings) [10], papuamides (HIV inhibitory macrocyclic depsipeptides) [11], polytheonamides (cytotoxic linear polypeptides) [12], cyclotheonamides (thrombin and serine protease inhibitors) [13], perthamides (anti-inflammatory cyclopeptides) [14][15], solomonamides [16] and

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• involvement of carboxylesterase (EC 3.1.1.1) is probable even though the participation of other hydrolases cannot be excluded [42][43]. Carboxylesterase belongs to the large class of α/β serine hydrolases, is located in the lumen of the endoplasmic reticulum of cells in many tissues, and is highly expressed

Isotopically labeled sulfur compounds and synthetic selenium and tellurium analogues to study sulfur metabolism in marine bacteria

• Nelson L. Brock,
• Christian A. Citron,
• Claudia Zell,
• Martine Berger,
• Irene Wagner-Döbler,
• Jörn Petersen,
• Thorsten Brinkhoff,
• Meinhard Simon and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 942–950, doi:10.3762/bjoc.9.108

• -serine to L-cysteine. Elemental sulfur, hydrogen sulfide, or thiosulfate can be funneled via the lithotrophic sulfur oxidation (Sox) pathway to sulfate [18][19][20][21][22]. Analogous degradation steps for the selenium and tellurium derivatives of DMSP (dimethylseleniopropionate, DMSeP, and

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• in animal models of ALS and in the study of other diseases where glutamate toxicity plays an essential role. In addition to dysregulation of glutamate levels in ALS patients, recent studies have also detected elevated levels of D-serine (Figure 3), an activator/co-agonist of the N-methyl-D-aspartate

• (NMDA) ionotropic glutamate receptor, in the spinal cord of both ALS patients and transgenic mice carrying the SOD1 G93A mutation [17][18]. This increase in D-serine corresponded with a reduction of D-amino acid oxidase (DAO) in SOD1 mutant mice, the enzyme responsible for the metabolism of D-amino

• acids including D-serine. Interestingly, a new mutation in the D-amino acid oxidase (DAO) gene has been recently characterized to contribute to fALS [19]. This R199W DAO mutation inhibits the function of DAO, increases ubiquitin-containing aggregates, and reduces cell viability when expressed in

De novo synthesis of D- and L-fucosamine containing disaccharides

• Daniele Leonori and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 332–341, doi:10.3762/bjoc.9.38

• bacterium. In 2001, the P. aeruginosa pilin O-linked glycans were found to be linear trisaccharides that are covalently attached to serine (Figure 1). The O-glycans contain a D-fucosamine residue at the protein-binding site. This unusual monosaccharide is not present in eukaryotes, and therefore may be used

An improved synthesis of a fluorophosphonate–polyethylene glycol–biotin probe and its use against competitive substrates

• Hao Xu,
• Hairat Sabit,
• Gordon L. Amidon and
• H. D. Hollis Showalter

Beilstein J. Org. Chem. 2013, 9, 89–96, doi:10.3762/bjoc.9.12

• Michigan, Ann Arbor, MI 48109-1065, USA 10.3762/bjoc.9.12 Abstract The fluorophosphonate (FP) moiety attached to a biotin tag is a prototype chemical probe used to quantitatively analyze and enrich active serine hydrolases in complex proteomes in an approach called activity-based protein profiling (ABPP

• evaluated against isolated protein mixtures and different rat-tissue homogenates, showing its ability to specifically target serine hydrolases. We also assessed the ability of FP–PEG–biotin to compete with substrates that have high enzyme turnover rates. The reduced protein-band intensities resulting in

• biological processes. In this regard, fluorophosphonate (FP) probes have been extensively used in activity-based protein profiling (ABPP) in proteomic studies [1][2]. FP probes, specifically designed to target serine hydrolases, originate from diisopropyl fluorophosphonate (DFP) [3][4]. DFP is a serine

Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

• Rajendra Surasani,
• Dipak Kalita,
• A. V. Dhanunjaya Rao and
• K. B. Chandrasekhar

Beilstein J. Org. Chem. 2012, 8, 2004–2018, doi:10.3762/bjoc.8.227

• short reaction time (Table 6, entry 2). The chiral purity of the product was determined by chiral HPLC using Chiral Pak AD-H column. Amino acids without extra coordinating groups gave good coupling yields (Table 6, entries 3, 6 and 7). Coupling of L-serine(O-t-Bu)-OMe (6d) with 1c resulted in moderate

• yield of the product in 3 h (Table 6, entry 4). The catalytic system developed by us for the coupling of amino acid esters with N-protected 7-azaindoles was ineffective for L-proline (6f), L-serine (6g), and L-glutamic acid (6h) (Table 6, entries 8–10). This may be ascribed to the fact that these amino

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• of sequential mutations on the adsorption of such synthetic AFGP analogues onto ice surfaces, and to corroborate the molecular mechanism of antifreeze activity. Recently, we published the synthesis of monosaccharide-based AFGP analogues containing glycine, proline and serine instead of alanine

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