Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• cyclization with the aid of HCl followed by pyridinium dichromate (PDC) oxidation (Scheme 8). Schmidt and co-workers [39] described an efficient route involving RCM and SM coupling towards the synthesis of 8-aryl-substituted coumarin 64, a natural product isolated from the plant Galipea panamensis. To this

• route to construct the dibenzocyclooctadiene lignan core of the natural product schisandrene via SM coupling and RCM as key steps. In this context, the SM reaction of boronic acid 102 with bromoaldehyde 103 in the presence of Pd2(dba)3 and the S-Phos ligand provided the cross-coupling product 104 (82

Efficient catalytic alkyne metathesis with a fluoroalkoxy-supported ditungsten(III) complex

• Henrike Ehrhorn,
• Janin Schlösser,
• Dirk Bockfeld and
• Matthias Tamm

Beilstein J. Org. Chem. 2018, 14, 2425–2434, doi:10.3762/bjoc.14.220

• metallacyclobutadiene (MCBD) intermediates [12]. Ongoing progress in the development of highly active homogeneous alkyne metathesis catalysts (Figure 1) has increased the value of this method in natural product and materials chemistry. The contributions from our group to the development of alkyne metathesis catalysts

The mechanochemical synthesis of quinazolin-4(3H)-ones by controlling the reactivity of IBX

• Md Toufique Alam,
• Saikat Maiti and
• Prasenjit Mal

Beilstein J. Org. Chem. 2018, 14, 2396–2403, doi:10.3762/bjoc.14.216

• highlights the advancement of quinazolin-4(3H)-ones synthesis chemistry and may find application in the context of mechanochemical reactions towards natural product synthesis and pharmaceutical chemistry. Experimental General methods. Ball-milling experiments were carried out open to atmosphere and at room

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• source of inspiration for insecticides [1][2]. Among natural product-based insecticides, spinosyns are a novel kind of green insecticides with broad insecticide spectrum. Spinosyns, derivatives of bioactive substances produced by the soil actinomycete Saccharopolyspora spinosa [3], have been widely

Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I

• Pamarthi Gangadhar,
• Sayini Ramakrishna,
• Ponneri Venkateswarlu and
• Pabbaraja Srihari

Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206

• strongylodiol H 9 in 85% yield (Scheme 4). Though the 1H NMR and 13C NMR spectra of the synthesized product were in full agreement with that of the reported natural product [10], the specific rotation of our synthetic product was determined as [α]D25 = +42.2 (c 0.81, CHCl3), and for the natural product it was

• natural product as 9a which is the enantiomer of the proposed structure 9 (Figure 3). Further, to reconfirm the structural revision, we synthesized the other enantiomer of strongylodiol H. Towards this we proceeded for the stereoselective reduction of prochiral ketone 17 with (R)-CBS as the catalyst

• optical rotation for 9a {[α]D25 = −40.2 (c 0.72, CHCl3)} was found to be in accordance with that reported for the isolated natural product {[α]D25 = −43.8 (c 0.35, CHCl3)} [10]. Thus, the total synthesis of the natural product (−)-strongylodiol H has been accomplished successfully. As the proposed

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• green alga Caulerpa taxifolia, exhibits antiproliferative activities as well as wound healing abilities with the latter resulting from rapid transformation to the highly reactive 1,4-dialdehyde, oxytoxin 2 (4) [4][5][6]. Oxytoxin 2 (4) is itself a natural product, produced by the mollusc Oxynoe olivacea

• of the enolester containing natural product to a 1,4-dialdehyde, which then undergoes Paal–Knorr pyrrole formation. Structurally simplified n-pentyl- and cyclohexylmethyl-dialdehydes were synthesized and found to undergo similar pyrrole forming reactions with pentylamine. These reactions were also

Bi-mediated allylation of aldehydes in [bmim][Br]: a mechanistic investigation

• Mrunesh Koli,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2018, 14, 2198–2203, doi:10.3762/bjoc.14.193

• ]; ionic liquid; Introduction The metal-mediated Barbier-type allylation of aldehydes has drawn considerable attention, because the resultant homoallylic alcohols are versatile intermediates for natural product synthesis [1][2][3][4][5][6][7]. The reaction, carried out in organic solvents, water, mixed

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• aromatics, heteroaromatics and fused aromatic and heteroaromatic systems with a variety of substituents to C–H amination using a wide range of heterocyclic amines. The functionalisation of molecules that are natural product-like such as 32c is demonstrated by the authors, which is an excellent example of

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• stereoselective synthesis. Additionally, the applications of these reagents in natural product synthesis are also covered. Keywords: hypervalent iodine reagents; iodoarenes; natural products; oxidative cyclization; spirocyclic compounds; Review 1. Introduction The chemistry of spirocyclic compounds is a well

• ). Furthermore, the absolute configuration of 88 was assigned by its single crystal X-ray analysis. 3.3. Application of spirolactams in natural product synthesis In 2001, Ciufolini and co-workers [103] employed PIDA (15) as an electrophile during the synthesis of naturally occurring tricyclic azaspirane

• 49 was converted to natural product 95 in few chemical steps. 4. Synthesis of spirocarbocycles 4.1. Using stoichiometric amounts of iodine(III) reagents Furthermore, O-silylated phenolic compound 96 was spirocyclized to spirocarbocyclic compound 97 in 95% yield using bridged iodine(III) reagent 28 as

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• ; Introduction Carbon–carbon bond formation is the fundamental and central transformation of synthetic organic chemistry. The elaboration and extension of a carbon framework via a series of carbon–carbon bond-forming reactions are extremely important for medicinal chemistry and agrochemical and natural product

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• enantioselectivities (90–94% ee), as shown in Scheme 5. The synthetic utility of this novel methodology was demonstrated through the total synthesis of the natural product (−)-psychotriasine (Scheme 5) and the biologically active compound AG-041R (Scheme 1). By using another type of organocatalyst, such as L

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• type 7 (B1, B2 = nucleobases). Structure of the natural product muraymycin A1 (44) and design concept of nucleosyl amino acid (NAA)-modified (partially) zwitterionic oligonucleotides of type 48 formally derived from structures 45–47 (B1, B2 = nucleobases). Structure of Letsinger's modified

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• ; cyclisation; fluorination; gauche effect; hypervalent iodine; oxazolines; Introduction Marine and terrestrial natural product bioprospecting has established a broad spectrum of structurally complex, bioactive metabolites containing the venerable 2-oxazoline unit [1][2]. This diversity is exemplified by the

Chlorination of phenylallene derivatives with 1-chloro-1,2-benziodoxol-3-one: synthesis of vicinal-dichlorides and chlorodienes

• Zhensheng Zhao and
• Graham K. Murphy

Beilstein J. Org. Chem. 2018, 14, 796–802, doi:10.3762/bjoc.14.67

• materials [7][8]. And as there is an abundance of chlorine-containing natural products, the synthesis of chlorinated functional groups, such as allyl- and vinyl chlorides, can represent challenging obstacles that practitioners of natural product synthesis must surmount [9][10][11][12]. More commonly, allyl

Volatiles from the xylarialean fungus Hypoxylon invadens

• Jeroen S. Dickschat,
• Tao Wang and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

• (2), another widespread fungal volatile, a plant growth promoting effect and an induction of systemic resistance in plants against fungi was observed [5]. The significant biological effects of these and other fungal volatiles recently resulted in a considerable interest of natural product chemists

• possibilities and retention indices were not available for all cases. All six constitutional isomers were obtained from commercial suppliers and compared to the natural product, establishing the identity of 15 and 3,4-dimethoxytoluene, for which an identical retention index and the best MS match was determined

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• . This constituted the key step of the first total synthesis of (30S)-apratoxin E and its (30R)-epimer. Comparing the spectroscopic data of these two diastereomers with those of natural apratoxin E unambiguously confirmed that (30R)-apratoxin E was the natural product and that (30S)-apratoxin E was

• constituted the key step of a nine-step total synthesis of the eastern fragment of jatrophane diterpene Pl-3, which is a complex natural product with high promising biological activities, such as antiproliferative activity and inhibition of the efflux-pump activity of multidrug resistance P-glycoprotein. The

• prepiscibactin through five supplementary steps, including Zn(II)-induced thiazolidine formation followed by lactamization. On the basis of NOE methods, the synthetic prebiscibactin was found spectroscopically indistinguishable from the natural product. More recently, excellent results were also reported by

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• natural product is 6-nonyl-2H-pyran-2-one. The antimicrobial and cytotoxic effects of the synthetic volatiles are also reported. Keywords: enantioselective synthesis; gas chromatography; mass spectrometry; natural products; volatiles; Introduction A large variety of volatile organic compounds from

• ethylmagnesium bromide gave 22 that was subsequently oxidised with PCC to the target compound 10. Comparison of the natural product to synthetic 10 established their identity by same retention time and mass spectrum. The mass spectrum of one of the two main compounds (11a) in the headspace extracts (Figure 2B

• 11 were separable by GC on a homochiral stationary phase, one of which matched the natural product in terms of same retention times and mass spectra (Figure 3). To clarify the relative and absolute configuration of the natural stereoisomer of 11 an enantioselective synthesis was performed (Scheme 5

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• as highly attractive building blocks for our project. A literature search revealed that compound 1 is in fact a natural product. It was isolated from the trunk bark of the Taiwanese tree Hernandia nymphaeifolia (Hernandiaceae) in 1996 [10]. No data on the biological activities of this alkaloid have

• been reported so far. Further, this literature search showed that two total syntheses of isoquinoline 1 had been published even before its identification as a natural product (Figure 1). In 1963, Franck and Blaschke [11] obtained 1 by dehydrogenation of its 1,2,3,4-tetrahydro analogue (which itself had

• naphthalene-derived natural product plumbagin. In fact, trapping 1-metalated isoquinoline 3 with Eschenmoser’s salt gave the aminomethyl derivative 5 in 37% yield. Chromatographic separation from starting material 3 (recovered yield: 32%) was unproblematic. Surprising results were obtained in our

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• been discussed [11], but due to the lack of functional groups, tetraoxaadamantanes have remained largely laboratory curiosities. It is worth noting that the 2,4,10-trioxaadamantanes, which are orthoesters, are well known [12][13], and the natural product muamvatin [14] is a 2,6,9-trioxaadamantane

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• diastereomer was assigned by X-ray analysis. Finally, one of the products was selectively reduced to provide a functionalized analogue of streptopyrrolidine, a marine natural product isolated from Streptomyces sp. As shown in Table 1, our studies started with the synthesis of dimer 2a using azlactone 1a in the

• significant anti-angiogenesis activity [31]. It is worth mentioning that this product has three consecutive stereocenters and different sites of variation from the original natural product. The hydride comes from the less hindered side of the ketone moiety, leading to the formation of a hydroxy group in cis

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• Xinli Pan Nicole Domin Sebastian Schieferdecker Hirokazu Kage Martin Roth Markus Nett Department of Biochemical and Chemical Engineering, Technical Biology, Technical University Dortmund, Emil-Figge-Strasse 66, 44227 Dortmund, Germany Leibniz Institute for Natural Product Research and Infection

• . aurantiacus 114-95T, we fed the strain with 13C-labeled glucose and, subsequently, searched for characteristic mass shifts in its metabolome. This approach led to the discovery of a new natural product, of which the isotope pattern is indicative for a diterpene originating from the methylerythritol phosphate

• natural product discovery. By comparing the ion chromatograms of cultures that were grown in the presence or absence of singly labeled glucose, it might be possible to identify terpenoid natural products in a complex metabolic background. To validate the feasibility of this approach, we chose the

Sulfation and amidinohydrolysis in the biosynthesis of giant linear polyenes

• Hui Hong,
• Markiyan Samborskyy,
• Katsiaryna Usachova,
• Katharina Schnatz and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2017, 13, 2408–2415, doi:10.3762/bjoc.13.238

• before or after the specific sulfonation step. The sequence of the sulfotransferase is a useful probe to uncover related gene clusters in public sequence databases. Sulfonation remains a rare and relatively poorly understood modification in natural product biosynthesis [27][28][29][30]. As our

• understanding of their specificity improves, sulfotransferases have been deployed to increase the structural diversity of several classes of natural products [31][32][33]. The slf genes of polyene biosynthesis reported here represent an additional starting point for such natural product diversification

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• displayed more potent activities than the parent natural product (Scheme 26) [63]. In their synthesis, 5-bromo-1H-indole was converted to the corresponding functionalized oxime 73 upon the action of ethyl bromopyruvate oxime in the presence of Na2CO3 in 60% yield. The adduct was transformed into carboxylic

Synthesis of substituted Z-styrenes by Hiyama-type coupling of oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane

• James R. Vyvyan,
• Courtney A. Engles,
• Scott L. Bray,
• Erik D. Wold,
• Christopher L. Porter and
• Mikhail O. Konev

Beilstein J. Org. Chem. 2017, 13, 2122–2127, doi:10.3762/bjoc.13.209

• ][17][18][19][20][21] and enyne metathesis [22][23]. We became interested in the cross-coupling of cyclic siloxanes in the context of preparing trisubstituted Z-styrenes for the synthesis of natural product targets [24]. Heliannuol A was the first member of a family of allelopathic [25][26][27

• of helianane. Conclusion In summary, we have confirmed the Hiyama cross-coupling of cyclic siloxanes is an efficient route to Z-trisubstituted styrenes that are useful for the synthesis of natural product frameworks. Although yields are low under the conditions attempted, a proof of concept has been

18-Hydroxydolabella-3,7-diene synthase – a diterpene synthase from Chitinophaga pinensis

• Jeroen S. Dickschat,
• Jan Rinkel,
• Patrick Rabe,
• Arman Beyraghdar Kashkooli and
• Harro J. Bouwmeester

Beilstein J. Org. Chem. 2017, 13, 1770–1780, doi:10.3762/bjoc.13.171

• ) for a compound isolated from the brown alga Dictyota dichotoma [30] was suggested (Scheme 2C). The same natural product is known from the higher plant Aglaia odorata [31], but in this case the reason for the assignment of the reported absolute configuration is unclear, because no optical rotation has