Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• ]. Macrocyclization of bifunctional building blocks containing diacid/diisonitrile and diamine/diisonitrile [37]. Synthesis of steroid-biaryl ether hybrid macrocycles by MiBs [38]. Synthesis of biaryl ether-containing macrocycles by MiBs [39]. Synthesis of natural product-inspired biaryl ether-cyclopeptoid

• macrocyclizations [44]. Synthesis of steroid–aryl hybrid cages by sequential 2- and 3-fold Ugi-4CR-based macrocyclizations [46]. Ugi-MiBs approach towards natural product-like macrocycles [47]. a) Bidirectional macrocyclization of peptides by double Ugi reaction. b) Ugi-4CR for the generation of exocyclic diversity

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• . Hence, the natural product 1 was available through this domino metathesis strategy featuring dienediyne 8 in 10 steps from (S)-citronellal (5) in 14.5% overall yield. Conclusion In summary, we have accomplished two short and efficient catalytic routes from (S)-citronellal (5) to the guaiane

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• ; Introduction Marine soft corals are important sources of biologically active compounds, which made them attractive targets for natural product chemists. Soft corals of the genus Clavularia (class Octocorallia, order Alcyonacea, family Clavulariidea), are prolific sources of numerous biologically active

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• assembled by solution-phase synthesis and an open-chain analogue of the natural product was obtained. Keywords: jasplakinolide; marine natural products; Negishi coupling; polyketides; stereoselective synthesis; Introduction Our program on the synthesis of biologically active natural products with peptide

• partial structures is driven by an interest in the chemistry of photoreactive amino acids and heterocycles that may find application in photoaffinity labelling. Knowing the binding of a natural product to a biological target at atomic resolution, as it is the case for the cyclodepsipeptide jasplakinolide

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• ]. As artemisinin has poor solubility and bioavailability, several derivatives of this natural product like artesunate and artemether were developed and are currently used in combination with other drugs for the treatment of malaria [4]. However, the exact mechanism of action of this endoperoxide

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• Information File 1). As previously described, the minimum inhibitory concentration (MIC) of 1 improves by alkylation of the indole moiety as seen for 3 [16] even 1 and 3 show a good activity against MRSA. Although for all other tested compounds no better activity than that of the original natural product 1

A novel and efficient synthesis of phenanthrene derivatives via palladium/norbornadiene-catalyzed domino one-pot reaction

• Yue Zhong,
• Wen-Yu Wu,
• Shao-Peng Yu,
• Tian-Yuan Fan,
• Hai-Tao Yu,
• Nian-Guang Li,
• Zhi-Hao Shi,
• Yu-Ping Tang and
• Jin-Ao Duan

Beilstein J. Org. Chem. 2019, 15, 291–298, doi:10.3762/bjoc.15.26

• reactivity, shorter reaction times, and higher yields of the target compounds. Meanwhile, these flexible approaches to the phenanthrene derivatives would be expected to provide significant references to material chemistry, pharmaceutical agents and natural product synthesis. Experimental General remarks All

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• has been highlighted in a number of complex natural product syntheses. In this review, we have systematically summarized various oxidative radical strategies developed for the ring-opening and cyclization of cyclopropane derivatives. Despite these advances, there still exist opportunities for

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• ][6][7][8]. For example, Jacquinet, Lopin-Bon and co-workers presented the preparation of CS oligomers with different sulfation motifs, starting from a single GlcA-GalNAc disaccharide precursor easily obtained by depolymerization of the natural product [9][10][11][12][13]. CS tetrasaccharides

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• distinguishes between simple coumarins with substituents only at the benzene part (e.g., osthole, a natural product with Ca2+-channel antagonist activity) [9], coumarins with substituents at the pyrone part (e.g., warfarin, a synthetic clinically used anticoagulant) [10], and heteroannellated coumarins, in

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• derivatives. Their structures could only be unambiguously determined by comparison to all isomers with different substitution patterns. The substitution pattern of the main compound from H. griseobrunneum, the new natural product 2,4,5-trimethylanisole, was explainable by a polyketide biosynthesis mechanism

• that was supported by a feeding experiment with (methyl-2H3)methionine. Keywords: constitutional isomerism; gas chromatography; mass spectrometry; natural products; volatiles; Introduction Fungi release a large number of different volatiles that belong to all kinds of natural product classes [1

• (Scheme 1). Comparison of the GC retention index of the natural product (I = 1225) to the retention indices of all six standards narrowed the possible structures down to those of 2,4,5-trimethylanisole (I = 1225) and 2,3,5-trimethylanisole (I = 1227), while all other isomers could be ruled out. The final

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• glycal scaffolds are versatile building blocks with multiple applications in the field of natural product synthesis [6], the development of new asymmetric synthetic sequences with stereochemical diversity is still of high interest. Different approaches have been reported for the asymmetric synthesis of

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• of rapamycin) [34]. This natural product, isolated from Streptomyces hygroscopicus, was one of the first protein–protein interaction stabilizers reported: it first binds to its receptor (i.e., FKBP12) with high affinity, after which the FKBP12-rapamycin complex will associate with TOR resulting in

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• clinical infections. In S. aureus, virulence is mainly mediated by quorum sensing, a bacterial cell-to-cell communication system based on the secretion of signal molecules [9][10][11]. The natural product hamamelitannin (1) has been identified as a non-peptide analogue of RIP (RNAIII-inhibiting protein

• , Foodborne Toxin Detection & Prevention Research Unit, Agricultural Research Service, United States Department of Agriculture, Albany, CA 94710, USA 10.3762/bjoc.14.260 Abstract Interfering with bacterial cell-to-cell communication is a promising strategy to combat antimicrobial resistance. The natural

• product hamamelitannin and several of its analogues have been identified as quorum sensing inhibitors. In this paper the synthesis of pyrrolidine-based analogues of a more lead-like hamamelitannin analogue is reported. A convergent synthetic route based on a key ring-closing metathesis reaction was

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• their phenotype in response to changes in population density, regulating virulence and biofilm formation when most impactful to the host organism [5]. This process is mediated by signalling molecules such as PQS, and natural product structures 1–8 analogous to PQS may provide interspecies QS-modulator

• these species were grown in the presence of the compounds. The results for E. coli ESS are shown in Figure 2, split into the natural product series, the series of analogues with a saturated side chain, and the truncated series of analogues. As can be seen in Figure 2A, natural product 1 resulted in

• replacement of the N-Me of 4 with the methylthiomethylene substituent of 7, nor epoxidation of 4’s side chain to give 8, offered any improvement in the biological activity. The result for 8 is particularly intriguing, as this natural product was noted to have the strongest effect upon the growth of H. pylori

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