The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• , the asymmetric Diels–Alder (D–A) reaction between the N-sulfonamide-3-hydroxy-2-pyridone-based dienes 52 and different dienophile substrates was developed using the bifunctional cis-2-trialkylaminoindanol organocatalyst ent-41 [56]. We show herein the reactivity of this family of dienes with several

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

• substances were detectable on the cocoon surface for months during hibernation. Structurally, piericidins consist of a pyridone core attached to polyene side chains of variable size, a structural and physiochemical feature of ubiquinone. Therefore, it is not surprising that piericidins are potent inhibitors

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

• Kristen K. Merritt,
• Kevin M. Bradley,
• Daniel Hutter,
• Mariko F. Matsuura,
• Diane J. Rowold and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 2348–2360, doi:10.3762/bjoc.10.245

• -letter GACTSB DNA alphabet. This was an alternative to the AEGIS nucleotides 2-amino-8-(1’-β-D-2’-deoxyribofuranosyl)imidazo[1,2-a]-1,3,5-triazin-4(8H)-one (trivially named P) and 6-amino-5-nitro-3-(1’-β-D-2’-deoxyribofuranosyl)-2(1H)-pyridone (trivially named Z) (Figure 2), which give a GACTZP six

OligArch: A software tool to allow artificially expanded genetic information systems (AEGIS) to guide the autonomous self-assembly of long DNA constructs from multiple DNA single strands

• Kevin M. Bradley and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 1826–1833, doi:10.3762/bjoc.10.192

• (trivially named B), 2-amino-8-(1’-β-D-2’-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)one (trivially named P), and 6-amino-5-nitro-3-(1’-β-D-2’-deoxyribofuranosyl)-2(1H)-pyridone (trivially named Z) (Figure 2). In both cases, conversion is facilitated by forcing polymerases to mismatch AEGIS

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• derivatives streptazones B1 (1), B2 (2), C (3), the 4-pyridone derivative streptazone D (4) with a pentadienyl side chain, and streptazolin (5) (Figure 1) [8]. Streptazolin is produced by several streptomycetes [8][9][10][11][12], and is formed biosynthetically by a polyketide mechanism [13]. The respective

An efficient method for the construction of polysubstituted 4-pyridones via self-condensation of β-keto amides mediated by P₂O₅ and catalyzed by zinc bromide

• Liquan Tan,
• Peng Zhou,
• Cui Chen and
• Weibing Liu

Beilstein J. Org. Chem. 2013, 9, 2681–2687, doi:10.3762/bjoc.9.304

• 1a–1k could be easily converted into their corresponding 4-pyridone 2a–2k. All the reactions proceeded smoothly and afforded the desired product in good to excellent isolated yields (72–90%) in 4 h. This transformation appears quite tolerant with respect to the positions of the substituents on the

• In summary, we have established an improved efficient synthetic protocol for the synthesis of 4-pyridone derivatives by a sequence of intermolecular dehydration of β-keto amides in the presence of phosphorus pentoxide (P2O5), 1,3-acyl migration and intramolecular dehydration. Comparing to the similar

New syntheses of 5,6- and 7,8-diaminoquinolines

• Maroš Bella and
• Viktor Milata

Beilstein J. Org. Chem. 2013, 9, 2669–2674, doi:10.3762/bjoc.9.302

• .9.302 Abstract The synthesis of 5,6- and 7,8-diaminoquinoline derivatives starting from angularly annelated selenadiazoloquinolones is presented. Simple chlorination of the pyridone ring followed by reductive deselenation of the 1,2,5-selenadiazole ring afforded novel 4-chloro-o-diaminoquinolines

• -benzoselenadiazole skeleton while the pyridine ring can be obtained by transformation of the pyridone core [15]. The synthesis of 7,8-diaminoquinoline (3) starting from selenadiazolo[3,4-h]quinolone 1 is depicted in Scheme 1. In the first step, the aromatization of the pyridone ring by chlorination with POCl3 in DMF

Investigating the continuous synthesis of a nicotinonitrile precursor to nevirapine

• Ashley R. Longstreet,
• Suzanne M. Opalka,
• Brian S. Campbell,
• B. Frank Gupton and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2013, 9, 2570–2578, doi:10.3762/bjoc.9.292

• malononitrile) and bypass the pyridone intermediate used in the original CAPIC synthesis (Scheme 2a) by effecting the ring closure under Pinner reaction conditions (Scheme 2b) [14]. We set out to investigate the possibility of performing a continuous synthesis of 2-bromo-4-methylnicotinonitrile starting from

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

• instances different names are commonly used by the synthetic community (i.e. pyridone and pyridinone). Furthermore, in most cases throughout this review only the syntheses of the free-based form of the parent drugs is discussed although these are commonly formulated in their prescription form as salts

• readily prepared by chlorination of 2-pyridone (1.42) with phosphorous oxychloride (Scheme 8) [31][32]. The resulting primary alcohol 1.45 is then subjected to a second SNAr reaction with 4-fluorobenzaldehyde [33]. A Knoevenagel condensation of the aldehyde functionality in compound 1.47 with

• substituted 2-pyridones (Scheme 9) [34][35]. This protocol is closely related to the Hantzsch pyridine synthesis and offers access to a wide range of products with well-defined regioselectivity. The simple undecorated parent 2-pyridone (1.42) can be somewhat harder to access but is obtained in a linear

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• -alanine. The key step to access the enantiopure pyridone intermediate was achieved by a gold-mediated cyclization. Finally, various transformations afforded the natural product in a few steps and good overall yield. Keywords: epimyrtine; gold; gold catalysis; heterocycles; hydroamination; quinolizidine

• enantiopure α and β-aminoynones was successfully used in our group to access pyrrolidinone and pyridone heterocycles via a gold-mediated approach [19][20]. The use of β-aminoynone intermediates for the synthesis of 2,3-dihydropyridones was recently developed by Georg [21] (Scheme 1). This strategy involves

• lithium acetylide to furnish the β-aminoynone 2 with a yield of 71%. With this key building block in hand, efforts were directed toward the gold-mediated intramolecular hydroamination for the construction of the chiral pyridone intermediate 3. For this, PPh3AuSbF6 generated in situ from a 5 mol % mixture

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• addition to its interesting bioactivity, lyconadin A presents a significant synthetic challenge by virtue of its unique pentacyclic skeleton, which contains six stereocenters and a pyridone ring. It is therefore not surprising that 1 has attracted the attention of the organic synthesis community. The first

• for synthesis. Herein, we provide an account of our studies directed toward the construction of this alkaloid. Specifically, we describe our efforts to prepare advanced intermediates that could be employed in the aforementioned pyridone annulation and tandem radical cyclization processes. In the

• functional-group manipulations. Based on the aforementioned model study [11], 7-exo–6-exo tandem radical cyclization of phenyl selenoester 4 was expected to produce ketone 3. Disassembly of the pyridone moiety of 4 according to our annulation protocol [14] revealed thioester 5 as a suitable precursor. 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

• condensation to give new 3-alkenyl-4,5,6,7-tetrahydroisoxazolo[4,3-c]pyridine-4-ones, which are masked forms related to the acylpyridone natural products. Keywords: aldol reaction; fused-ring systems; heterocycles; isoxazole; metalation; pyridone; Introduction The 3-acyl-4-hydroxypyridin-2-one moiety 1

• 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

• conditions (toluene, reflux, PTSA, 1.3 mol equiv) to give the 3-alkenyl compound 8a (63%). This revised protocol has not yet been extended to the reaction of pyridone 6 with other aldehydes, but has been routinely employed for elaboration of the dehydro version 4 [16]. The acylpyridone antifungal natural

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• central problem we wished to address was the preparation of the 3-alkyl-2-pyridone moiety of 36 by an unusual [3 + 3] construction developed in our laboratory [80]. This chemistry (Scheme 7) promotes the condensation of a cyanoacetamide 37, with an enone or enal 38, in the presence of t-BuOK in DMSO

• ] upon the resultant 42 delivered the requisite 41 in 87% yield. Happily, it transpired that the conjugate addition chemistry of 41 is indeed controlled exclusively by the quinolyl ketone. This enabled the conduct of our pyridone-forming sequence, which in the present case, however, had to be implemented

• in the slightly modified form seen in Scheme 10. Thus, Michael addition of 2-methyl cyanoacetamide converted 41 into a mixture of diastereomers of hemiamidals 47 and 48. Attempts to force this mixture to advance to the desired pyridone under basic conditions yielded uniformly unsatisfactory results

A practical two-step procedure for the preparation of enantiopure pyridines: Multicomponent reactions of alkoxyallenes, nitriles and carboxylic acids followed by a cyclocondensation reaction

• Christian Eidamshaus,
• Roopender Kumar,
• Mrinal K. Bera and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2011, 7, 962–975, doi:10.3762/bjoc.7.108

• pyridines in Table 1 are depicted in their predominant tautomeric form as found in CDCl3 at ambient temperature. Interestingly, the pyridone/pyridinol equilibrium seems to depend on the substituents at the C-2 or C-6 side chains. In general, a hydrogen bond-acceptor seems to stabilize the pyridone tautomer

• , whereas the pyridinol tautomer is favored when a hydrogen bond-donor is present. Compound 37 exists exclusively as pyridone tautomer, but after desilylation the resulting product, with a free hydroxy group in the side chain, strongly prefers the pyridinol tautomer. It seems reasonable to assume that the

• pyridone tautomer is stabilized through an internal hydrogen bond between a silyl ether or a tertiary amine moiety of the side chain as observed for compounds 22 and 24. Moreover, we found that the equilibrium is strongly influenced by the solvent. In CDCl3 pyridine 40 exclusively exists in its pyridone

Desymmetrization of 7-azabicycloalkenes by tandem olefin metathesis for the preparation of natural product scaffolds

• Wolfgang Maison,
• Marina Büchert and
• Nina Deppermann

Beilstein J. Org. Chem. 2007, 3, No. 48, doi:10.1186/1860-5397-3-48

• precursors for the tandem conversions, 7 was deprotected and acylated with butenoic acid and pentenoyl chloride to give 8 and 10. However, first attempts to convert the bis-olefin 8 via RORCM to the bicyclic target structure failed and only pyridone derivative 9 was isolated in small quantities along with

• . Ruthenium based precatalysts used in this study. RORCM of 2-azabicycloalkenes 5 to bicyclic scaffolds 6. RORCM of 7-azabicycloalkenes 8 and 10 to pyridone 9 and isoindole scaffold 11. RORCM of 7-azabicycloalkenes 13 and 16 to bicyclic scaffolds 14, 15, 17 and 18. Conditions A: 10 mol % 1, C2H4, 3 equiv

Asymmetric aza-Diels- Alder reaction of Danishefsky's diene with imines in a chiral reaction medium

• Bruce Pégot,
• Olivier Nguyen Van Buu,
• Didier Gori and
• Giang Vo-Thanh

Beilstein J. Org. Chem. 2006, 2, No. 18, doi:10.1186/1860-5397-2-18

• highly efficient procedure for the synthesis of 2-substituted-2,3-dihydro-4-pyridone derivatives through the aza-Diels-Alder reaction under 'green chemistry' conditions. The reaction has been found to perform well at room temperature in ionic liquids using no Lewis acid catalyst or organic solvent.[30

Efficient synthesis of 5-substituted 2-aryl- 6-cyanoindolizines via nucleophilic substitution reactions

• Eugene V. Babaev,
• Natalya I. Vasilevich and
• Anna S. Ivushkina

Beilstein J. Org. Chem. 2005, 1, No. 9, doi:10.1186/1860-5397-1-9

• lead to substitution of oxo/oxy-group to chlorine giving the products 2 a – d. (It is well known that analogous 2-hydroxypyridines which exist in the pyridone tautomeric form can be easily converted to 2-chloroderivatives by reaction with POCl3.).[7] Indeed, heating of indolizinones 1 a – d in POCl3 at