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

Design of a novel tryptophan-rich membrane-active antimicrobial peptide from the membrane-proximal region of the HIV glycoprotein, gp41

• Evan F. Haney,
• Leonard T. Nguyen,
• David J. Schibli and
• Hans J. Vogel

Beilstein J. Org. Chem. 2012, 8, 1172–1184, doi:10.3762/bjoc.8.130

• ; NMR solution structure; membrane interactions; peptides structure–function relationship; Introduction Antimicrobial peptides (AMPs) continue to attract significant attention as potential alternatives to conventional antibiotics. A large number of AMP sequences have been reported in the literature

• experiments. This work was supported by the Canadian Institutes of Health Research program for “Novel Alternatives to Antibiotics”. HJV is an Alberta Innovates – Health Solutions Scientist.

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

Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

• Tobias Knobloch,
• Gerald Dräger,
• Wera Collisi,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2012, 8, 861–869, doi:10.3762/bjoc.8.96

• . Keywords: ansamitocins; antibiotics; antitumor agents; mutasynthesis; natural products; Introduction Natural products still play an important role as lead structures for the treatment of infectious diseases and cancer. However, natural products have lost some of their attraction for the development of

• multienzymes are responsible for setting up the complete carbon backbone of both ansamycin antibiotics [21][22][23][24]. More precisely, the biosynthesis of ansamitocins relies on a type I modular polyketide synthase (PKS), with 3-amino-5-hydroxybenzoic acid (1, AHBA) [20] as the starter unit followed by chain

Synthesis and biological evaluation of nojirimycin- and pyrrolidine-based trehalase inhibitors

• Davide Bini,
• Francesca Cardona,
• Matilde Forcella,
• Camilla Parmeggiani,
• Paolo Parenti,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2012, 8, 514–521, doi:10.3762/bjoc.8.58

• potential fungicides or antibiotics [13], such as trehalostatin (4) [1][14] and some iminosugar glycoconjugates, e.g., 5 or MDL 25,637 (6) [1][15][16] (Figure 1). In this work we report the synthesis and the biological activity of a small set of nojirimycin- and pyrrolidine-based iminosugar derivatives and

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

• shown to increase the production of certain antibiotics [14]. Of each mutant obtained in this study, usually three independent clones were isolated, and secondary metabolite production was determined in three parallel cultivations for each clone. The variability of production between different clones

• well as the so-called cpk cluster, have been deleted, and which also lacks plasmids SCP1 and SCP2. Furthermore, strain M1154 was generated from strain M1146 by introducing mutations into the genes rpoB and rpsL, which has been shown to result in an increased production of certain antibiotics [15]. We

Aldol elaboration of 4,5,6,7-tetrahydroisoxazolo[4,3-c]pyridin-4-ones, masked precursors to acylpyridones

• Raymond C. F. Jones,
• Abdul K. Choudhury,
• James N. Iley,
• Mark E. Light,
• Georgia Loizou and
• Terence A. Pillainayagam

Beilstein J. Org. Chem. 2012, 8, 308–312, doi:10.3762/bjoc.8.33

• elfamycin antibiotics [5]. Interest has also been stimulated in these metabolites by the use of the entomopathogenic fungi such as Cordyceps sp., many of which contain pyridone metabolites, in traditional Chinese medicine to strengthen the immune system and improve cognitive function. Farinosone A (2d) from

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

• genus includes producers of important antibiotics such as the aminoglycoside gentamycin [15] and the antitumor antibiotics lomaiviticins A and B (Micromonospora lomaivitiensis) [16]. Here the results of the headspace analyses of M. aurantiaca are described. Besides compounds from other classes, several