Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• aminotrifluoromethylation of alkenes in an intramolecular version was reported by Zhang and co-workers in 2017 (Scheme 14) [33]. Langlois’ conditions with tert-butyl hydroperoxide and a catalytic amount of copper(II) triflate were used to prepare a series of CF3-containing indoline, pyrrolidine, lactam and lactone

Diastereoselective Mannich reactions of pseudo-C₂-symmetric glutarimide with activated imines

• Tatsuya Ishikawa,
• Tomoko Kawasaki-Takasuka,
• Toshio Kubota and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 2473–2477, doi:10.3762/bjoc.13.244

• lactones in good to excellent yields [4][5]. One of the most intriguing features of this protocol is the fact that the enantiomers at the lactone part were readily obtained only by the selection of the tertiary amines employed in the reaction. It is quite apparent that this success is, at least in part

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• ; metabolites; Introduction The group of steroid plant hormones called brassinosteroids (BS) currently comprises about 70 compounds [1]. It is generally accepted that only few of them (such as brassinolide, castasterone, epibrassinolide, etc.), possessing 2α,3α-, (22R,23R)-diol groups, B-lactone, and 6-ketone

• cyclic thiocarbonate 15 as a key reaction step gave the expected Δ2-olefin 16 in an excellent yield (Scheme 2). Subsequent deacetylation of 16 then afforded 24-episecasterol (17). An alternative procedure to Δ2-steroids was applied for the preparation of the B-ring lactone derivative 21 (Scheme 3). The

• mesylation of diol 18 produced dimesylate 19, which was treated with zinc dust and sodium iodide in refluxing DMF (Tipson–Cohen reaction [16]) to give, after deacetylation, B-lactone olefin 21 in 96% yield. 2α,3α- and 2β,3β-epoxides of type 4 and 5 Olefins of type 3 are evident intermediates for the

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

• José Enrique Barquera-Lozada and
• Gabriel Cuevas

Beilstein J. Org. Chem. 2017, 13, 1969–1976, doi:10.3762/bjoc.13.192

• rearrange to yield one or potentially two elemanolide configurations. The schkuriolide (1, Scheme 1) is a sesquiterpene lactone, specifically a (Z,E)-germacranolide, named melampolide, that coexists in the same natural source with the elemanschkuhriolide (3), which is an elemanolide with a stereochemistry

• considered when a prediction of the configuration of an elemane is determined before a Cope rearrangement. Finally, we studied the role the γ-lactone ring plays in the transformation of germacranes into elemanes. Takeda et al. carried out a series of experiments, which proved that γ-lactone rings prevent the

• Cope rearrangement of (Z,E)-germacranolides when the ring is closed but not when the ring is open [41]. A study of the Cope rearrangement in open ring (Z,E)-germacranolide 1 (7, Figure 3) and (E,E)-germacranolide 4 (8, Figure 3) was done in order to analyze the effect of the lactone ring. Figure 3

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• macrolactone ring are designated as C1–C11 (with the carbonyl carbon of the lactone ester group as C1), those in the carbon-linked (“upper”) side chain as C12–C20 and those of the oxygen-linked (“lower”) side chain as C1’–C16’ (with the carbonyl carbon of the exocyclic ester group as C1’). Finally, in our

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• theranostic applications. Keywords: BODIPY conjugates; cancer targeting; drug delivery; liposomes; natural compounds; sesquiterpene lactone trilobolide; Introduction Targeted (smart) drug delivery is a method for specific delivering of an active compound preferentially to some cells or tissues in the human

• describe the synthesis and application of a fluorescent construct (further called construct 6, depicted in Scheme 1) based on a green-emitting BODIPY dye and trilobolide–cholesterol (Tb-ChL) in a liposome formulation. Trilobolide (Tb, Figure 1) is a potent natural compound of the sesquiterpene lactone

• active construct 6 from the liposomes. Further tests are necessary to confirm this hypothesis. Conclusion In summary, in order to develop a drug delivery system for potential theranostic applications, we prepared a submicron liposome-based formulation of a cytotoxic agent, sesquiterpene lactone

Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• lactone 6-heptyl-4-hydroxypyran-2-one (6-HHP) within the scaffold of the Corynebacterium ammoniagenes FAS (a bacterial type I system). In an engineered reaction sequence, an initial FAS module was designed to produce SCFA as acyl esters, which are in a second FAS module elongated to the triketide and

• cyclized to the final lactone (Figure 4). A similar synthetic route can be found in norsolorinic acid synthesis, in which a fully reducing fungal FAS collaborates with a non-reducing PKS [4][56], as well as in resorcylic acid lactone synthesis, in which two iterative PKS systems work in sequence [57]. We

• -domain functional knockout, to synthesize the final lactone PK. The knockout in the AT-domain hinders the uptake of acetyl-CoA and encodes for modules acting in sequence. Acknowledgements M.G. thanks Dieter Oesterhelt for valuable discussions on FAS and PKS catalytic mechanisms, and continuous support

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• also pursued identical routes to this subunit. As shown in Scheme 5, this sequence started from L-leucine (26) which was first converted with nitrous acid to the hydroxy acid 27, which proceeds with retention of the configuration due to intermediate lactone formation after generation of the diazonium

A concise and practical stereoselective synthesis of ipragliflozin L-proline

• Shuai Ma,
• Zhenren Liu,
• Jing Pan,
• Shunli Zhang and
• Weicheng Zhou

Beilstein J. Org. Chem. 2017, 13, 1064–1070, doi:10.3762/bjoc.13.105

• other hypoglycemic agents. Only a few methods have been found in the literature about the synthesis of 1. It was reported that aryllithium reacted with per-hydroxy-protected D-glucono-1,5-lactone at −78 °C to obtain the lactol, followed by reduction with a large bulk silyl hydride in order to get high β

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• effective synthetic protocol to access [6,6]-bicyclic lactone moieties through a regio- and stereoselective intramolecular Mizoroki–Heck cross-coupling reaction followed by a 6π-electrocyclization. This method enabled the first synthesis of the elusive CD fragment of the Erythrina alkaloid DHβE. Preliminary

• pharmacological evaluations support the notion that the key pharmacophores of DHβE are located in the A and B rings. Keywords: DhβE; Mizoroki–Heck cross-coupling reaction; 6π-electrocyclization; [6,6]-bicyclic lactone; vinyl halide; Introduction The neuronal nicotinic acetylcholine receptors (nAChRs) have been

• ring and the B–C ring, which contrasts a mutational-computational study by Bermudez and co-workers suggesting that the lactone carbonyl is a hydrogen bond acceptor and hence locating the key pharmacophores in the C and D rings [9]. In order to weigh these hypotheses against one another, we have

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• phosphonates were compatible with the hydroxylation condtions, while monoalkyl phosphonate gave the phosphoryl lactone as product. Exploration of substrate scope showed that both electron-donating groups (such as Me, OMe) and electron-withdrawing groups (such as F, Cl, Br, CF3) are tolerable. 1.2.2.3 Phenol as

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• , 1-indanone has been obtained in 80% yield. Interestingly, when aluminum chloride was added to the lactone in benzene, the yield of this reaction decreased (30%) [34]. Irradiation of esters 44 possessing the photoremovable 2,5-dimethylphenacyl group in benzene or cyclohexane solutions led to free

Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• system bearing a γ-lactone terminus constitutes the right half of the molecule. To date, no structurally related natural products are known except for its demethyl congener butyrolactol B that was also isolated from the same strain and has an isopropyl group instead of the tert-butyl terminus [9]. Very

• intriguing feature of this molecule is the highly oxygenated carbon chain in which eight hydroxy groups, one of which is used for lactone formation, are contiguously aligned. A 1,3-diol is a common structural element in aliphatic polyketides because the incorporation of malonate-precursors gives rise to the

• with a parameter set optimized for 1JCC 50 Hz, cross peaks derived from the intact 13C2 acetate units were detected for the carbon pairs mentioned above (Table 1, Figure 4a). According to the incorporation result of the doubly labeled acetate, malonyl-CoA is not the extender unit for the lactone (C-1

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• stage. This modification results in an experimentally tractable δ-lactone 9 instead of the 14-membered macrolide, 6-deoxyerythronolide B. Notably, the two methyl centers in the lactone have opposite configurations (for clarity, that at C-2 will be referred to as D-configured, and that at C-4 as L), and

• (Figure 9), (2RS)-[2-2H]methylmalonyl-CoA (10) was prepared and provided to DEBS 1-TE (along with starter unit butyryl-CoA (11) and NADPH (12)), knowing that solely the (2S)- isomer would be utilized. Analysis by mass spectrometry and NMR of the triketide lactone product 13 showed that only a single

• lactone product). Sequestering of intermediates by the ACP domains has been proposed as a source of configurational stability at C-2 [82]. However, as all direct study of this question to date by NMR has failed to reveal any direct contact between modular PKS ACP domains and their attached substrates [83

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• ; pheromones; Introduction The lactone motif is found in many compounds that are used in chemical communication. Among them, macrocyclic lactones are an important class because of their biosynthetic availability and their inherent compound properties. During the biosynthesis of macrocyclic lactones, a fatty

Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase

• Hui Hong,
• Yuhui Sun,
• Yongjun Zhou,
• Emily Stephens,
• Markiyan Samborskyy and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2016, 12, 2164–2172, doi:10.3762/bjoc.12.206

• gene cluster for biosynthesis of the polyketide β-lactone ebelactone in Streptomyces aburaviensis has shown that, contrary to a recently-published proposal, the ebelactone polyketide synthase faithfully follows the colinear modular paradigm. Keywords: colinearity; ebelactone; enzyme catalysis

• the third is the PKS for the β-lactone ebelactone, a potent esterase inhibitor from Streptomyces aburaviensis 2a,b (Figure 1) [30]. These examples are particularly interesting as potential model systems because the chemical outcome of the two successive extensions catalysed by the iterative module is

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• diastereoisomeric lactone 52 in 76% yield. This lactone (52) was converted to enediol 53 in a further few steps. The second THF ring was then established using an epoxidation–cyclization sequence. Thus, asymmetric Sharpless epoxidation (SAE) [103][104] yielded an intermediary oxirane (not shown in Scheme 12) which

Diastereoselective synthesis of 3,4-dihydro-2H-pyran-4-carboxamides through an unusual regiospecific quasi-hydrolysis of a cyano group

• Mikhail Yu. Ievlev,
• Oleg V. Ershov,
• Mikhail Yu. Belikov,
• Angelina G. Milovidova,
• Viktor A. Tafeenko and
• Oleg E. Nasakin

Beilstein J. Org. Chem. 2016, 12, 2093–2098, doi:10.3762/bjoc.12.198

• presence thereof, but all acids promote only the iminolactone decyclization process without traces of lactone derivative 4 (Table 2). It is also important to note that during the reaction pathway (Scheme 3) a carbonyl-assisted carbonitrile hydration effect (CACHE) was occured. The carbonyl group, through

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• for the oxidative production of valuable intermediates [264][265][266][267][268][269]. The asymmetric oxidation of 3-substituted cyclopentane-1,2-diones 87a–f is an efficient tool in organic synthesis for the preparation of unsymmetrical γ-lactone acids 88a–f with high optical purity and good yields

• (Table 6). These γ-lactone acids are valuable substrates for the synthesis of compounds with potentially useful pharmacological properties, such as homocitrates, alkyl- and aryl-substituted nucleosides [270][271][272]. The reaction starts with an asymmetric epoxidation of the substituted cyclopentane-1,2

• -dione 87a to form epoxide 89a. The second step involves the Baeyer–Villiger oxidation of epoxide 89a to peroxide 90a followed by the rearrangement into intermediate 91a. The latter is hydrolyzed by H2O to form dicarboxylic acid 92a, which is cyclized under the acidic conditions to γ-lactone acid 88a

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• imine at the α-position (Table 1, entry 9). By using [RhCl(cod)]2, the α,β-unsaturated lactone was also converted to the product with a small improvement in the yield (Table 1, entry 11). Acrylamide 2i also gave the corresponding β-aminoamide 4Ai in a low yield (Table 1, entry 12). In the reaction using

• α,β-unsaturated lactone 2h, the β-lactam anti-3Ah that has a hydroxy group on the side chain was obtained in a low yield (Table 1, entry 11). This result was of interest because the reaction is applicable to the synthesis of ezetimibe. Ezetimibe is an inhibitor of the cholesterol transporter Niemann

• ). BF3·Et2O was found to be the most suitable Lewis acid, and the desired β-lactam (anti-3Bh) was obtained in moderate yield (Table 2, entry 9). Based on these results, we applied this reaction to the synthesis of ezetimibe (Scheme 3). The reaction of imine 1B with lactone 2j proceeded smoothly and gave

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

• annelated with a δ-lactone and a cyclopentanone or oxidation products of the latter. Aflatoxin biosynthesis has been studied since the late 1960s and has attracted attention, because the polyketide undergoes a series of oxidative rearrangements, which drastically alter the molecular scaffold. Due to the

• lactone that is decarboxylated towards the xanthone [103]. Studies with recombinant AflM and a lack of isolatable intermediates however made it clear that the order of steps in demethylsterigmatocystin (107) formation needs to be carefully re-evaluated [100]. Methylation by an O-methyltransferase and

• isoprenoid biosynthesis. The designated branching modules of lactone and glutarimide-producing PKS show similar designs: a branching domain (B or X), which is flanked by a KS and an ACP domain (Scheme 20b and c). In vitro reconstitution experiments with the branching module of the macrolide rhizoxin (130

Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells

• Bernardas Morkunas,
• Balint Gal,
• Warren R. J. D. Galloway,
• James T. Hodgkinson,
• Brett M. Ibbeson,
• Yaw Sing Tan,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2016, 12, 1428–1433, doi:10.3762/bjoc.12.137

• types of quorum sensing systems. Two of the QS signaling systems in P. aeruginosa utilise N-acylated-L-homoserine lactones (AHLs) as signalling molecules [20][21][22]. The rhl system utilises N-butanoyl-L-homoserine lactone (BHL) and it’s cognate receptor RhlR [20][21][22]. The las system utilises N-(3

• -oxododecanoyl)-L-homoserine lactone (OdDHL) and it’s cognate receptor LasR (Figure 1) [20][21][22]. Interlinking these two AHL signalling systems is a third signaling system utilising a quinolone signalling molecule (termed Pseudomonas quinolone signal, PQS) [20] to form an intricate hierarchical signaling

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• configurational assignment is ambiguous in this case, the NMR data and the fact that no γ-lactone is formed strongly support the trans-arrangement of the two functional groups as depicted. Under similar conditions (5 mol % Pd(PPh3)4, 90 °C, 3 d) the isopropyl-substituted ketone 2 furnished a mixture of the

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

• favoured attack at the more reactive δ-lactone carbonyl instead of that of the methyl ester. Pleasingly, this was indeed realised at the next stage; performing a nitro-Mannich lactamisation cascade on 13 with formaldehyde and butylamine in methanol afforded lactam 15 in 63% yield, possessing the