Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• under mild conditions and could be applied to peptides containing other nucleophilic and aromatic amino acids, such as serine, phenylalanine or tyrosine. Keywords: alkynes; C–H functionalization; gold catalysis; hypervalent iodine; peptides; Introduction Alkynes have always been important building

• other aromatic amino acids, such as phenylalanine or tyrosine (products 5c and 5d). Serine and proline containing dipeptides 5e and 5f could also be obtained in 64% and 53% yield, respectively. The reaction was therefore general for dipeptides bearing tryptophan at the C-terminus. On the other hand

Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• alcohols and bulky acids: Cherney and Wang observed an elimination of a serine derivative during esterification experiments [23]. During conversion of substituted benzyl alcohols to amines under Mitsunobu conditions, elimination also occurred [24]. Dehydration under Mitsunobu conditions has been applied in

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• , requires a tight regulatory network in predatory myxobacteria [80]. This is also reflected in the genome of M. xanthus DK1622, which features an unusual high duplication frequency of genes encoding regulatory proteins like serine-threonine kinases and enhancer binding proteins (EBPs) [43]. EBPs are

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• D-serine. Due to the presence in conidia, serinocyclines have also been hypothesized to play a role in the virulence of M. anisopliae. Chemical analysis of the entomopathogenic fungus B. bassiana yielded beauvericin (43), a depsipeptide with alternating methylphenylalanyl and hydroxyisovaleryl

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• phosphatase B (PtpB) [31] and serine protease [32]. The focus of this review is on pyridoacridine-related metabolites as one of the many interesting groups of alkaloids produced from marine sources. They are generally produced by marine sponges, ascidians [33] and tunicates [34] and they are structurally

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• amino acids like glycine, alanine or serine in the native process of N-terminal methionine excision (NME) [43]. This process exposes Ser2 at the N-terminus for subsequent N-terminal oxime ligation. It has to be noted that the incorporation of Aha, as known [42][44], can hamper NME and therefore delivers

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• higher bioactivity compared to their corresponding homodimers [57]. BMP receptors (BMPRs) belong to the group of serine/threonine kinase transmembrane receptors and are subdivided into type I and II receptors [64][65]. There are three type I receptors, namely BMPR-IA (also known as ALK-3, activin

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• derivatives of many amino acids often become annoyingly strenuous due to the necessity of employing protecting groups, on one or more of the amino acid functionalities, during the synthetic sequence. However, in the case of hydroxyamino acids such as hydroxyproline, serine, threonine, tyrosine and 3,4

• ; organocatalysis; serine; threonine; tyrosine; Introduction Any adept researcher within the field of organic synthetic chemistry will be mindful of the outstanding importance of amino acids as inexpensive chiral starting materials in the synthesis of a nearly infinite variety of synthetic end products. This

• the copper salt with hydrogen sulfide. This methodology has subsequently been employed in a more generic sense as a preparative method for synthesis of acrylic side-chain derivatives of amino acids such as lysine, ornithine, tyrosine and serine [6][7][8], having modified the original technique by

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

• Vicky Gheerardijn,
• Jos Van den Begin and
• Annemieke Madder

Beilstein J. Org. Chem. 2014, 10, 2566–2572, doi:10.3762/bjoc.10.268

• functionalities on the nucleoside. As proof of principle and with the catalytic serine–histidine–aspartate catalytic triad of serine proteases in mind, we illustrate the preparation of three different nucleosides equipped with three functional amino acids containing hydroxy, imidazole, amine and carboxylate

• assembly of the desired chain without DNA damage. In the current study, we have chosen to couple three amino acids, which contain functional groups commonly used in SELEX approaches to modify DNA or RNA, to 5-iodo-2’-deoxyuridine. We describe the direct and linker-less introduction of histidine, serine and

• accomplished under standard conditions and the corresponding derivative 5 was isolated and purified without problems. As a second example we decided to employ serine as amino acid for introduction onto the nucleoside. In view of the earlier illustrated need for imidazole protection during introduction of

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• Supporting Information File 1). The di- and trivalent guest strands 8–14 (Figure 1C, D) were synthesized by solid phase peptide synthesis using a standard Fmoc-protocol (Figure 3). Therefore the serine derivatives 15 and 16 (Figure 1E) and a water-soluble linker molecule were used. The purity of the guest

• strands is estimated to be >95% based on 1H NMR spectra (see Supporting Information File 1). The syntheses of the multivalent host and guest strands are described in detail in Supporting Information File 1. First of all, the selectivity of the complexation of the unprotected serine derivatives 17 and 18

• towards α- and β-CD was investigated by ITC experiments. The structures of the host–guest complexes were elucidated by NMR spectroscopy. The 1-adamantane-functionalized serine 17 shows complexation of α- and β-CD, forming 1:1 complexes. In both cases the adamantane moiety binds into the CD cavity, which

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• -workers led to a reassignment of its structure and that of the parent molecules, such as polyoxin A (69) [24][25][26]. The synthesis of the E-isomer of polyoximic acid started from protected D-serine 70, which was converted into diazoketone 71 by reacting a mixed anhydride with diazomethane (Scheme 10

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• is transferred to the glycan by a sialyltransferase. The serine or threonine residues in the O-glycosylation sites serve as acceptors for GalNAc using a convenient GalNAc transferase. This unit can be galactosylated by a galactosyltransferase and both, the monosaccharide and the disaccharide, may be

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• -α-amino acids serine and threonine, (2S,3S)-3-hydroxyleucine can be found as a substructure of several bioactive natural products. This structural motif often serves as a 'three-way-junction', as for instance in azinothricin [1], citropeptin [2], kettapeptin [3], pipalamycin [4], dentigerumycin [5

• protecting group pattern. The most promising strategy to achieve these goals appeared to be a variation of the ex-chiral pool synthesis developed by Zhu and co-workers [32]. They have utilized the stereocenter of D-serine in a diastereoselective Grignard addition to protected D-serinal as the key step of

• [32], we have employed their 7-step synthesis of a stereoisomerically pure amino alcohol as the key intermediate. According to the previously reported protocol, D-serine (2) was transformed into protected derivative 3 (4 steps, 59% overall yield, Scheme 1). Alcohol 3 was then oxidized to a D-serinal

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• the identification of new potent and selective ligands of ionotropic and metabotropic glutamate receptors (GluRs). To this aim, bicycle compound Ib was designed and synthesised from D-serine as novel [2.3]-spiro analogue of L-Glu. This frozen amino acid derivative was designed to further limit the

• from D-serine, their synthesis was accomplished in 10 steps in good overall yield. After an extensive investigation on the best synthetic approach, key intermediate 20 was successfully prepared by an efficient rhodium-catalyzed cyclopropanation of a terminal double bond of compound 18 with ethyl

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