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

• moiety attached to the scaffold. These compounds could find application as potent antibiotics, protease inhibitors or as cholesterol absorption modifiers (Scheme 37) [18]. In this particular reaction, the scaffolds were obtained by reacting the complex isocyanide 118 with different aldehydes and β-amino

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• introduce a thiol linker by Huisgen-type cycloaddition which can principally be utilized to create tumor targeting conjugates. In bioactivity tests, only those new ansamitocin derivatives showed strong antiproliferative activity that bear an ester side chain at C-3. Keywords: ansamitocins; antibiotics

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• , University of Cambridge, Lensfield Road, Cambridge CB2 1QW, UK 10.3762/bjoc.10.34 Abstract Polyether antibiotics such as monensin are biosynthesised via a cascade of directed ring expansions operating on a putative polyepoxide precursor. The resulting structures containing fused cyclic ethers and a

• tailoring step as well as polyether formation. Keywords: antibiotics; biosynthesis; natural products; polyketides; Streptomyces; synthetic biology; Introduction Monensin A (1) from Streptomyces cinnamonensis is one of the most prominent and best-studied of the polyether class of complex polyketides, an

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• vinyl ether, this approach was successfully applied in the key steps of the total synthesis of a member of the thiomarinol class of marine antibiotics (Scheme 19) [66][67]. More recently, Hall and co-workers described the total synthesis of a complex 20-membered marine macrolide, palmerolide A, a potent

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• explored a flow microreactor system for sequential transformation towards fluoroquinolone antibiotics such as ciprofloxacin via both inter- and intramolecular SNAr reactions (Scheme 10) [70]. Starting from the acylation reaction of (N-dimethylamino)acrylate with 2,4,5-trifluorobenzoic acid chloride

• [18F]-radiolabeled molecular imaging probes. Flow microreactor synthesis of dipeptides. Flow synthesis involving SNAr reactions. Flow synthesis of fluoroquinolone antibiotics. Highly controlled formation of PFPMgBr. Selective flow synthesis of photochromic diarylethenes. Flow microreactor system for

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

• substructures. This structural motif can be found in many natural products, such as iminosugars (7 and 9), peptide antibiotics (8), sphingosines and their derivatives (10 and 11, Figure 3). These naturally occurring polyhydroxylated compounds have attracted increasing interest from synthetic chemists, because

• of Garner’s aldehyde. Structures of some iminosugars (7, 9), peptide antibiotics (8) and sphingosine (10) and pachastrissamine (11). (a) i) Boc2O, 1.0 N NaOH (pH >10), dioxane, +5 °C → rt; ii) MeI, K2CO3, DMF, 0 °C → rt (86% over two steps); (b) Me2C(OMe)2, cat. p-TsOH, benzene, reflux (70–89%); (c

The total synthesis of D-chalcose and its C-3 epimer

• Jun Sun,
• Song Fan,
• Zhan Wang,
• Guoning Zhang,
• Kai Bao and
• Weige Zhang

Beilstein J. Org. Chem. 2013, 9, 2620–2624, doi:10.3762/bjoc.9.296

• -10-camphorsulfonic acid (CSA) in MeOH. Keywords: asymmetric dihydroxylation; chalcose; epimer; total synthesis; Introduction Chalcose (4,6-dideoxy-3-O-methyl-D-xylo-hexose, I [1][2]) is a structural component of many macrolide antibiotics, such as chalcomycin [3], neutramycin [4], and lankamycin [5

• sourced material and unsatisfactory overall yield. As part of our study concerning the structure–activity relationships and chemistry of new antibiotics, we sought to develop a reliable and efficient synthetic route starting from inexpensive, commercial sources to provide access to chalcose. We describe a

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• biosynthetic pathway. Keywords: antimycins; gene regulation; genome mining; natural products; Streptomyces; Review It is estimated that around 60% of all known antibiotics are derived from secondary metabolites made by filamentous actinomycete bacteria, most notably Streptomyces species [1]. Streptomyces

• neighbouring microbes [3]. In recent years genome sequencing has revealed that each Streptomyces species encodes many more specialised metabolites than it makes in laboratory culture, leading to new efforts to activate these so-called “silent pathways.” The number of known antibiotics made by Streptomyces

• host. This approach has already been used to identify novel chemical scaffolds of antibiotics produced by well-studied Streptomyces species [4][5][6] and to identify the biosynthetic gene clusters for commercially important antibiotics [7][8][9][10][11]. The latter allows cloning, optimisation and

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• ). Nalidixic acid is a prototype quinolone antibiotic that has been used extensively as an effective treatment against both gram positive and gram negative bacteria. In general, quinolone antibiotics act by interfering with the enzymes DNA-gyrase and/or topoisomerase of bacteria [55]. Moxifloxacin (1.102

• , Avelox) and levofloxacin (1.103, Levaquin) are two third-generation fluoroquinolone antibiotics which also appear amongst the top selling drugs. These compounds display similar SAR data [56]. For instance, in the case of moxifloxacin the fluorine atom in the C6 position enhances microbial activity while

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• discovery research. Several natural occurring anthracycline antibiotics. Total synthesis of daunomycinone 6 according to Hansen. Synthesis of simplified anthracycline derivatives. Retrosynthetic analysis of anthracycline aglycone mimics. Si: any silyl group. Synthetic route for the synthesis of various

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

• by Joullié and co-workers [2] and the X-ray analysis of the N-acetyl derivative of the natural product by Shiro et al. [3]. (+)-Furanomycin belongs to the smallest natural antibiotics [4]. Therefore, the compound found considerable interest in synthetic chemistry. Until today, five total syntheses

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• reference antibiotics (Table 4). Tetramate 2b was found to be active against virulent and resistant strains, such as methicillin and fluoroquinolone-resistant S. aureus and penicillin and/or erythromycin-resistant S. pneumoniae. Remarkably, tetramate 2b maintained the activities against all the strains and

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• amides in natural products including septacidin [3], teicoplanins [4], tunicaminyluracil-based antibiotics [5] (tunicamycins [6], corynetoxins [7], and streptovirudins [8]), the arylomycin glycopeptide antibiotics [9][10], maradolipids [11], plipastatin-type lipopeptides [12], Nod factors [13

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• ribonucleic acid polymerase. These compounds inhibit chain initiation of RNA synthesis in Staphylococcus aureus, a particularly infectious bacterial strain with reported drug resistance to the antibiotics vancomycin and methicillin [3]. Ripostatin A exists as an equilibrium mixture of ketone and hemiketal

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• synthesis of β-lactam antibiotics [58][85]. In this vein, the metal-independent character of the presented thermolysis of α-bromodiazoacetamides makes the transformation compatible with late-stage synthesis in medicinal chemistry. Additionally, in a preparative context, the formation of α-bromo-β-lactams

Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids

• Paweł Borowiecki,
• Małgorzata Milner-Krawczyk and
• Jan Plenkiewicz

Beilstein J. Org. Chem. 2013, 9, 516–525, doi:10.3762/bjoc.9.56

• or iodides, yielding novel optically active ionic liquids. Racemic salts were tested against a wide range of microorganisms. Keywords: antibiotics; antifungal agents; double derivatization; enzyme catalysis; ionic liquids; Introduction Aromatic heterocycles play a crucial role in medicinal

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• attention in recent years because of their broad biological activities [11][12] and therapeutic applications, ranging from antibiotics [13] to anticancer agents [14]. Moreover, the DKP moiety has been exploited as a peptidomimetic scaffold [15][16][17]. Structural unification of THBC and DKP pharmacophores

Multivalent display of the antimicrobial peptides BP100 and BP143

• Imma Güell,
• Rafael Ferre,
• Kasper K. Sørensen,
• Esther Badosa,
• Iteng Ng-Choi,
• Emilio Montesinos,
• Eduard Bardají,
• Lidia Feliu,
• Knud J. Jensen and
• Marta Planas

Beilstein J. Org. Chem. 2012, 8, 2106–2117, doi:10.3762/bjoc.8.237

• potential alternative to traditional antibiotics. To date, a very large number of antimicrobial peptides have been produced based on naturally occurring products or by de novo design, and most of them display a broad spectrum of antimicrobial activities [3][4]. Despite their remarkable structural diversity

Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups

• H. Bauke Albada,
• Alina-Iulia Chiriac,
• Michaela Wenzel,
• Maya Penkova,
• Julia E. Bandow,
• Hans-Georg Sahl and
• Nils Metzler-Nolte

Beilstein J. Org. Chem. 2012, 8, 1753–1764, doi:10.3762/bjoc.8.200

• ; medicinal organometallic chemistry; metallocenoyl; peptides; tryptophan; Introduction New antibacterial agents need to be discovered since established antibiotics are increasingly losing ground against resistant bacteria and at the same time the pipeline that is supposed to produce new antibiotics is

Synthetic studies towards bottromycin

• Stefanie Ackermann,
• Hans-Georg Lerchen,
• Dieter Häbich,
• Angelika Ullrich and
• Uli Kazmaier

Beilstein J. Org. Chem. 2012, 8, 1652–1656, doi:10.3762/bjoc.8.189

• ring system in a straightforward manner. Keywords: amidines; antibiotics; bottromycin; peptides; thiopeptides; Ugi reactions; Introduction Natural products are excellent sources as lead structures for the development of new antibiotics. Over millions of years microorganisms, such as bacteria and

• fungi, developed efficient defense strategies against their bacterial competitors [1][2][3]. Not surprising, a wide range of common antibiotics such as penicillin or vancomycin are natural products or derivatives thereof. In 1957 Waiswisz et al. reported a new antibiotic peptide isolated from the

• fermentation broth of Streptomyces bottropensis, called bottromycin [4][5][6]. This antibiotic inhibits the growth of a wide range of microorganisms by interfering with their protein biosynthesis [7][8][9][10][11][12]. In 1965 Nakamura et al. isolated closely related antibiotics from the strain Streptomyces No

Asymmetric one-pot sequential Friedel–Crafts-type alkylation and α-oxyamination catalyzed by a peptide and an enzyme

• Kengo Akagawa,
• Ryota Umezawa and
• Kazuaki Kudo

Beilstein J. Org. Chem. 2012, 8, 1333–1337, doi:10.3762/bjoc.8.152

• ][19][20]. Indoles with an oxygenated stereogenic carbon at the β-position of the ring, such as indolmycin [21][22] and diolmycin [23], are known as antibiotics (Figure 1). The framework of these compounds could be constructed though the conjugate addition of an indole to α,β-unsaturated aldehydes

Binaphthyl-anchored antibacterial tripeptide derivatives with hydrophobic C-terminal amino acid variations

• John B. Bremner,
• Paul A. Keller,
• Stephen G. Pyne,
• Mark J. Robertson,
• K. Sakthivel,
• Kittiya Somphol,
• Dean Baylis,
• Jonathan A. Coates,
• John Deadman,
• Dharshini Jeevarajah and
• David I. Rhodes

Beilstein J. Org. Chem. 2012, 8, 1265–1270, doi:10.3762/bjoc.8.142

• antibiotics [1][2], and of particular concern is the resistance to the cationic glycopeptide, vancomycin [3][4]. This challenge is being addressed in a number of ways, which include both detailed studies aimed at the further understanding of the mechanism of this resistance, as well as the development of new

Partial thioamide scan on the lipopeptaibiotic trichogin GA IV. Effects on folding and bioactivity

• Marta De Zotti,
• Barbara Biondi,
• Cristina Peggion,
• Matteo De Poli,
• Haleh Fathi,
• Simona Oancea,
• Claudio Toniolo and
• Fernando Formaggio

Beilstein J. Org. Chem. 2012, 8, 1161–1171, doi:10.3762/bjoc.8.129

• , Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 13883, Salmonella entereditis 13076, and Proteus mirabilis ATCC 10975. The well-known antibiotics bacitracin and tetracyclin (10 μg/disk) were used as controls. List of primary structures and abbreviations for the

Similarity analysis, synthesis, and bioassay of antibacterial cyclic peptidomimetics

• Workalemahu M. Berhanu,
• Mohamed A. Ibrahim,
• Girinath G. Pillai,
• Alexander A. Oliferenko,
• Levan Khelashvili,
• Farukh Jabeen,
• Bushra Mirza,
• Farzana Latif Ansari,
• Ihsan ul-Haq,
• Said A. El-Feky and
• Alan R. Katritzky

Beilstein J. Org. Chem. 2012, 8, 1146–1160, doi:10.3762/bjoc.8.128

• ; Introduction Diverse cyclic peptides, both natural and synthesized, are potent antibiotics [1][2][3]. Gramicidin S, vancomycine, bacitracin, polymixin B, colistin, valinomycin, actinomycin, and many more, have been tested and used clinically as antimicrobial and antifungal agents: It is believed that cyclic

• antibiotics roxithromycin and cefixime were used as positive controls. It is seen that peptidomimetic 37b exhibits moderate activity against Bordetella bronchiseptica, Micrococcus luteus, and Salmonella typhimurium. For a “bare” scaffold with no tailor-made substitution, this should be considered as an

Antibiotic and cytotoxic peptides

• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1144–1145, doi:10.3762/bjoc.8.127

• Journal of Organic Chemistry on “Antibiotic and cytotoxic peptides”: The fight against bacterial infections is in a critical phase. The excessive application of antibiotics in human therapy, and also in livestock breeding, leads to the rapid development of highly virulent bacterial strains resistant to

• the conventionally applied antibiotics. Consequently, the search for new antibiotically active compounds is of premier importance. On the other hand, highly cytotoxic peptides and peptide analogues, such as monomethyl auristatin E, are used as the “warhead” in antibody–drug conjugates for tumor