Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• thioester to a hydroxy group (d in Scheme 2). A Michael addition–lactonisation cascade leads to pyranones with a substituent in the 4-position 16 (e in Scheme 2). 3-Acylfuran-2-ones (19, 3-acyltetronates) are formed by acylation–Dieckmann condensation between 2-hydroxythioesters 18 and β-ketothioesters 17

• lactonisation yielding the pyran-2-one attached to the caged ring system [137]. 1.7 Furanones 1.7.1 Acylation–Dieckmann condensation: Tetronates. Tetronates (4-hydroxyfuran-2(5H)-ones, 145a/145b) are an abundant type of heterocycles with a broad spectrum of biological activities (Figure 5) [138][139]. In

• -activating FkbH-like protein, an acyl carrier protein (ACP) that intermediately carries the glycerate unit and a FabH-like protein that condenses the ACP-bound glycerate with an ACP-bound β-ketothioester in an acylation–Dieckmann condensation reaction cascade (Scheme 22) [139]. This scenario has been

Synthesis of ferrocenyl-substituted 1,3-dithiolanes via [3 + 2]-cycloadditions of ferrocenyl hetaryl thioketones with thiocarbonyl S-methanides

• Grzegorz Mlostoń,
• Róża Hamera-Fałdyga,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 1421–1427, doi:10.3762/bjoc.12.136

• described [1]. The latter substrates were prepared efficiently via acylation of ferrocene with in situ generated mixed anhydrides containing a trifluoroacetyl unit or, alternatively, by ferrocenylation of furan, thiophene or selenophene with mixed trifluoroacetyl anhydride. The obtained ferrocenyl

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• . The linker 4 is designed for functionalization of either commercial amino-modified oligonucleotides or amine-bearing polyamides. It contains an alkyne group for CuAAC and an activated ester for the acylation of amino groups. The linkers 5–7 of different lengths contain an azide group for CuAAC and a

• ) bearing either alkyne or azide groups were obtained via acylation of their N-terminal amine by the activated esters method in DMF in the presence of Hünig's base (see Supporting Information File 1 for experimental details). We have pursued several goals: 1) to synthesize a variety of modified MGBs with

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• . Acylation of the hydroxy group of quinidine resulted in complete loss of enantioselectivity, suggesting that hydrogen-bonding contacts between the catalyst’s hydroxy group and the substrate are important for organizing the transition state. Using catalytic quinine (25) the pseudo-enantiomer of the quinidine

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• these conditions, although this method had been successfully used for the alkylation and acylation of the tertiary alcohol function of analogous serine derived PHOX ligands [30]. Among various amines, 2,6-lutidine was finally identified as a suitable base for conversion to the desired derivatives in 67

• is available. The subsequent silylation or acylation of the hydroxy group gives access to a library of diverse NeoPHOX ligands. In this way the steric size and the coordination ability of the substituent at the stereogenic center can be tuned for a specific application. Structural motifs of

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• corresponding β-ketoenamines 2a–e were converted into different β-ketoenamides 3a–g by N-acylation with 2-pyridinecarboxylic acid derivatives. These β-ketoenamides were treated with a mixture of TMSOTf and Hünig’s base to promote the cyclocondensation to 4-hydroxypyridine derivatives. Their immediate O

• we reported on a new pyridine synthesis starting from symmetrically substituted 1,3-diketones 1a and 1b, respectively, that were converted into the corresponding β-ketoenamines and subsequently by N-acylation into β-ketoenamides such as 3a or 3b [1]. Their cyclocondensation followed by O-alkylation

• to this compound class the design of new derivatives is possible thus supplementing the existing collection of available 2,2´-bipyridines. Results and Discussion First we prepared the corresponding β-ketoenamines 2 required for the N-acylation step (Scheme 2). The known compounds 2a and 2b are

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• -controlled Michael reaction remained present. Accordingly, we chose to probe reactivity and establish relative stereocontrol using a close model system comprising pronucleophile 8 and furanyl nitroolefin 11 (Scheme 1). The δ-valerolactone pronucleophile 8 was synthesised by the enolate acylation of δ

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• aniline. The corresponding phenylurea can be prepared in high yield (96%), which is then subjected to C–H Suzuki–Miyaura coupling at room temperature (91%). Sequential deprotection and acylation with 2-chloronicotinoyl chloride result in boscalid in four steps in an overall yield of 86%, which compares

Reactions of N,3-diarylpropiolamides with arenes under superelectrophilic activation: synthesis of 4,4-diaryl-3,4-dihydroquinolin-2(1H)-ones and their derivatives

• Larisa Yu. Gurskaya,
• Diana S. Belyanskaya,
• Dmitry S. Ryabukhin,
• Denis I. Nilov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2016, 12, 950–956, doi:10.3762/bjoc.12.93

• , B under the superelectrophilic activation. N-Formylation and N-acylation of dihydroquinolinones 2. Superelectrophilic activation of the N-formyl group of compounds 5 and their reaction with benzene. Reactions of amides 1a–u with benzene (and other arenes) under superelectrophilic activation, leading

Hydroquinone–pyrrole dyads with varied linkers

• Hao Huang,
• Christoffer Karlsson,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 89–96, doi:10.3762/bjoc.12.10

• also investigated (vide infra), but did not produce satisfactory results. Settambolo et al. [20] reported a synthetic route starting from an acylation of pyrrole by phenylacetyl chloride via a Friedel–Crafts reaction, followed by reduction by NaBH4, and elimination to give the vinylpyrrole product

A convergent, umpoled synthesis of 2-(1-amidoalkyl)pyridines

• Tarn C. Johnson and
• Stephen P. Marsden

Beilstein J. Org. Chem. 2016, 12, 1–4, doi:10.3762/bjoc.12.1

• 4 [5] and the threonine tyrosine kinase inhibitor CFI-401870 (5) [6]. The 2-(1-amidoalkyl)pyridines are almost always synthesised by acylation of the related 2-(1-aminoalkyl)pyridines, which can be prepared by reduction of ketimines derived from 2-acylpyridines [5] or 2-cyanopyridines [6], addition

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• isobutene (36), an isomeric mixture of trans- and cis-fused [4.2.0]octanone was obtained (trans-38/cis-39 = 4:1). The more stable cis-bicycle 39 could be obtained by isomerization of trans-38 with base. Acylation with sodium hydride and dimethyl carbonate followed by methylation furnished β-keto ester 40

• construction of the cyclononene unit [49]. The synthesis started with a diastereoselective Evans syn-aldol reaction between substituted propanal 86 and E-crotonyl-oxazolidinone 85 (Scheme 9). The resulting secondary alcohol was silylated and the chiral auxiliary was cleaved with lithium borohydride. Acylation

Molecular-oxygen-promoted Cu-catalyzed oxidative direct amidation of nonactivated carboxylic acids with azoles

• Wen Ding,
• Shaoyu Mai and
• Qiuling Song

Beilstein J. Org. Chem. 2015, 11, 2158–2165, doi:10.3762/bjoc.11.233

• ][13][14][15][16][17][18][19][20][21], the acylation of amines with free carboxylic acids is still the most common method employed due to the availability of the starting materials and its relatively clean process feature, whereby water is the only byproduct in the transformation [22]. However

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• couplings with a Bestmann ylide linchpin have enabled direct lactone and lactam synthesis [12][13][14][15], including the preparation of macrolactones [16][17][18]. An extension of this methodology to γ-hydroxyenone substrates allows the preparation of α-alkylidene-γ-butyrolactones through tandem acylation

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

• efficient than the first. Other differences have been noted such as Friedel–Craft acylation in sulfuric acid that led to one product after chromatographic column purification, while in the second preparation, a mixture of two adducts was obtained after an absorbent-free purification. This may explain why

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• -iodoaniline, PPTS (pyridinium p-toluenesulfonate) and NaBH4 (64%) was followed by N-acylation of the aniline nitrogen atom (80%) provided the target precursor 10. The reaction of 7 with 1 equiv of tributyltin hydride was incomplete, but the use of 2.5 equiv of tributyltin hydride at fixed concentration ([7

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• ) Regioselective enzymatic acylation of natural products. Natural products are traditionally classified into groups of substances (terpenes, alkaloids, amino acids, lipids, etc), depending on their biosynthetic origin and on their chemical and structural features [19][20][21]. The complex structures of most of

• fungal β-N-acetylhexosaminidase evaluated [28]. Similarly, dimers of sylibin (11a,b, Figure 3) and dehydrosylibin, obtained by Novozyme 435-catalyzed acylation with the divinyl esters of dodecanedioc acid, were evaluated in terms of antioxidant activity and cytotoxicity [29]. The obvious hypothesis

• acylation [30]. As shown in Scheme 2, the protease thermolysin catalyzed the regioselective acylation of the side chain of paclitaxel (12) to give the 2’-vinyl adipate 12a in 60% isolated yields. Novozyme 435-catalyzed elaboration of this intermediate allowed either to hydrolyze the residual vinyl ester to

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• ketimine is followed by stoichiometric alkynylation with a trimethylsilyl-protected alkynyllithium reagent. Removal of the silyl and sulfinyl protecting groups allows for CuAAC with a resin-bound azide. Acylation of the amine followed by dehydration yields the active alpha-tetrasubstituted triazole [7

• -deprotection followed by acylation forms the triazole amide product [6][7][8]. N-[4-(Trifluoromethyl)benzyl]triazole 6c and morpholinyltriazole 6d are isolated in 76% and 72% yield, respectively. Cyclopentylamine-derived 6e and N-methylpiperazine-derived 6f provide additional choices for amine substituents

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• bromide gave the enyne product 166 (92%), which on further acylation of terminal alkyne with butanoyl chloride delivered compound 167 (82%). Then, it was subjected to an enyne metathesis with simple platinum salts such as PtCl2 and PtCl4 to give product 168 (79%). A subsequent reduction of the α,β

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• order to avoid downstream incompatibilities. The initial step was a Friedel–Crafts acylation of isobutylbenzene (10) with propionic acid (11) in the presence of excess triflic acid (12). The transformation was found to work very effectively and the acid catalyst was also tolerated in the subsequent 1,2

• (Friedel–Crafts acylation, 1,2-aryl migration and saponification) this report focuses on improved output by intensifying the overall sequence (Scheme 3). As such an in-line extraction is performed after the Friedel–Crafts acylation step, followed by dissolving intermediate 18 in trimethyl orthoformate and

Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors

• Joana Salta,
• Jens Dernedde and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2015, 11, 638–646, doi:10.3762/bjoc.11.72

• Schotten–Baumann acylation or by coupling employing HATU as reagent. The O-sulfation employing the SO3·DMF complex was optimized. It was crucial to follow this process by 700 MHz 1H NMR spectroscopy to ensure full conversion and to use a refined neutralization and purification protocol. Many of the

• route [24][27][28], whereas serinol (2) is commercially available. As a first approach to construct amide derivatives we envisioned the Schotten–Baumann acylation using acid chlorides. For this purpose a protection of the hydroxy groups of aminopyran 1 with the tert-butyldimethylsilyl (TBS) group was

Potential of acylated peptides to target the influenza A virus

• Daniel Lauster,
• Damian Pawolski,
• Julian Storm,
• Kai Ludwig,
• Rudolf Volkmer,
• Henry Memczak,
• Andreas Herrmann and
• Sumati Bhatia

Beilstein J. Org. Chem. 2015, 11, 589–595, doi:10.3762/bjoc.11.65

• of antiviral peptides by respective nanostructures will be perturbed or even inhibited. In conclusion, the acylation of those peptides as used in our study, and in previous studies does not resemble an advantage over other strategies of multivalent presentations. Volume size distribution profile of

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• -catalyzed ECA reactions During the early development of CA reactions, Grignard reagents were initially studied as potential nucleophiles for these reactions. Unfortunately, mixtures of the 1,4-addition and the acylation products were formed. Upon further investigation, it was discovered that the use of

• 1,4-addition of aryl amines to N-alkenoyloxazolidinones [244]. In that report, they sometimes obtained a mixture of products, where one was the desired 1,4-addition product and the other product resulted from the 1,4-addition and acylation of the amine (Scheme 35). The side product was formed in

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

• -dihydroxyphenylalanine (DOPA), many O-acyl side-chain derivatives are directly accessible via a particularly expedient and scalable method not commonly applied until recently. Direct acylation of unprotected hydroxyamino acids with acyl halides or carboxylic anhydrides under appropriately acidic reaction conditions

• renders possible chemoselective O-acylation, furnishing the corresponding side-chain esters directly, on multigram-scale, in a single step, and without chromatographic purification. Assuming a certain degree of stability under acidic reaction conditions, the method is also applicable for a number of

• more elaborate procedures for chemoselective O-acylation reactions, spur its further development, and finally to chronicle the informative, but poorly documented history of its development. Keywords: amino alcohols; chemoselectivity; DOPA; hydroxyamino acids; hydroxyproline; O-acylation

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

•  7). Compounds 30–34 were obtained through Friedel–Crafts acylation of 29 with corresponding acyl chlorides in 55–81% yield. Subsequent alkylation with geranyl bromide gave products 35–39 in moderate yields from 55 to 60%. Finally, p-toluenesulfonic acid (pTSA)-catalyzed cyclization afforded the

• target compounds 40 and 41 in 53 and 65% yield, respectively. The synthesis of the second series is shown in Scheme 8 [59]. Amberlyst 15 efficiently catalyzed the condensation of 1,3,5-trihydroxybenzene (29) with isoprene in 53% yield. The following Friedel–Crafts acylation gave the intermediates 43–46

• inhibited angiogenic processes in various in vitro and in vivo models [82][83]. The typical synthesis of genistein starts from 1,3,5-trihydroxybenzene (29, Scheme 10) [84]. After the Houben–Hoesch reaction or Friedel–Crafts acylation, the cyclization of the resulting hydroxyketone 59 in the presence of BF3