Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• equilibrium of the reaction can be pushed to the production of UDCA. An overview of reported enzymatic and chemoenzymatic cascades is summarized in Table 5 and Figure 6 [12][33][78][86][87][88][89][90][91][92][93][94]. From the comparison of the different routes, it can be observed that higher productions are

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

• labeling pattern in IPP and DMAPP (Figure 1) [8]. This feature has proven extremely useful to unravel complex cyclization cascades and carbon–carbon rearrangements in the biosynthesis of some terpenoids [9][10][11][12]. We anticipated that the resulting mass shifts could also be valuable in the field of

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

• different downstream signaling cascades. As the core component of these complexes, mTOR exhibits protein kinase activity and phosphorylates a variety of downstream meditators. One of the principal substrates of the mTORC2 complex is the serine/threonine kinase Akt, which gets activated upon phosphorylation

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

• established in four principal ways (Scheme 29). The biosynthesis of pyridinones (203, 207, 211 or 213) is mechanistically particularly diverse. It occurs via condensation reactions between carbonyl groups and nitrogen-containing functionalities, Michael addition–lactamisation cascades (similar to the

The EIMS fragmentation mechanisms of the sesquiterpenes corvol ethers A and B, epi-cubebol and isodauc-8-en-11-ol

• Patrick Rabe and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1380–1394, doi:10.3762/bjoc.12.132

• be a valuable source of information for many questions in natural product chemistry [23]. Many recent examples have shown how isotopic labelling experiments can unravel the complex and sometimes surprising cyclisation cascades that are catalysed by terpene cyclases in the conversion of simple linear

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• cyclopropene 97 reacted [93][94] to form the same products as the hydrazone 96 did directly when heated to 140 °C. Gold The work by the May group was soon followed by gold-promoted carbene/alkyne cascades. These cascades rely on Zhang’s discovery that the use of pyridine N-oxides allow for the formation of

• deuterium kinetic isotope effect of 2.34 was seen for C–H insertion with gold catalysis. Hashmi demonstrated the viability of dual gold catalysis for carbene/alkyne cascades with diynes like 109, which gave products from either a 1,2-methyl shift (not shown) or a C–H bond insertion to form enone 112 (Scheme

• . Platinum cascades. Tungsten cascade. Acknowledgements The authors are grateful to the Welch Foundation (grant E-1744) and the NSF (grant CHE-1352439) for financial support. J-L.S. is grateful for support by CBIP (UH) and the Studying Abroad Scholarship of Taiwan.

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• ) [63]. In 2010 and 2011, Wang demonstrated that the versatile β-unsaturated α-ketoesters 87 are capable of participating in multiple cascades, initiated by Michael addition of preformed stable enols 137 and 138. As a result, this methodology provided a highly efficient route to coumarins 139 and

• rings initiated by oxy/aza/sulfa-Michael addition In 2007, Wang and co-workers utilized 2-mercaptobenzaldehydes 163 and α,β-unsaturated systems as Michael acceptors, such as α,β-unsaturated oxazolidinones 164 and maleimides 52, in order to catalyze Michael aldol cascades to construct versatile

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• responses from a suite of receptors and creates patterns for diagnostic purposes that are beyond what can be achieved by the separate components alone. In fact, we are currently working to push this even further creating multicomponent cascades of reactions yielding a final result that the individual

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• mevalonate/deoxyxylulose-level for in vivo feeding experiments or oligoprenyl diphosphates for in vitro studies to understand the often complex cyclization cascades catalyzed by a single enzyme. In many cases, isotopes represent the only way of elucidating proposed hydride shifts, carbon–carbon

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• into products of interest [149]. Prospects and challenges for future biotechnological applications In order for CO2 biotransformation to target a broad range of commodity chemicals, the CO2-fixing enzymes must be used as part of multi-enzymatic cascades that convert CO2 through multiple steps [111][150

• order for these to be employed in suitable bioprocesses, where they may be assembled into multi-enzymatic synthetic cascades, suitable methodologies for facile recombinant expression need to be developed further. This will extend beyond simple expression of a single gene, and may require simultaneous

Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

• Christine Basmadjian,
• Fan Zhang and
• Laurent Désaubry

Beilstein J. Org. Chem. 2015, 11, 1017–1022, doi:10.3762/bjoc.11.114

• examined. In the course of these studies, numerous scaffolds were synthesized, including a furan, a cyclopentenone, an acyclic enone and even a naphthalenone. The diversity of these structural motifs lies in novel cascades of reactions originating from a common carbocationic manifold. Keywords

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• ][69][70]. In fact, the binding of BMP can induce different signaling cascades. Either the ligand binds to a preformed complex (PFC) consisting of a type I and II receptor, or the ligand mediates homodimerization of BMPR-I, followed by recruitment of BMPR-II (Figure 5b). The latter oligomerization mode

• , which is referred to as BMP-induced signaling complex (BISC), leads to internalization via caveolae and induces Smad-independent signaling cascades, resulting in alkaline phosphatase induction through p38 (mitogen-activated protein kinase (MAPK)) signaling cascade. Binding to PFCs triggers clathrin

• , which determine the three dimensional structure of the protein [59]. (b) Smad dependent and independent BMP signaling pathways. Smad-dependent signaling cascades are induced upon binding of the ligand to a preformed complex (PFC) of BMPR-I and BMPR-II and subsequent internalization via clathrin-mediated

Anionic sigmatropic-electrocyclic-Chugaev cascades: accessing 12-aryl-5-(methylthiocarbonylthio)tetracenes and a related anthra[2,3-b]thiophene

• Laurence Burroughs,
• John Ritchie,
• Mkhethwa Ngwenya,
• Dilfaraz Khan,
• William Lewis and
• Simon Woodward

Beilstein J. Org. Chem. 2015, 11, 273–279, doi:10.3762/bjoc.11.31

• , substituted phenyl, 2-thienyl) to ortho-C6H4(CHO)2 undergo cascades to tetracenes on simple admixture of LiHDMS, CS2 and MeI. Acene formation proceeds by [3,3]-sigmatropic rearrangement of xanthate anions followed by 6π electrocyclisations. The reactions are terminated by E2 or anionic Chugaev-type

• , the possibility of aromatisation of 6 through Chugaev [22] syn elimination. Finally the system of Scheme 2 provides a unique opportunity to probe if these rearrangements do indeed proceed from the neutral xanthates 1c or via the previously unprecedented 1d–2d–6d anionic cascades. Results and

• rearrangements of xanthates are normally considered to proceed via neutral species (such as 1c). The tetracenes 7 herein are not formed this way, instead the evidence here strongly suggests that the required [3,3]-6π–6π electrocyclic cascades takes place via anionic xanthate species before final capping with

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

• to the signaling cascades of pathological angiogenesis. Further criterion for inclusion in this survey was the presence of anti-angiogenic activity obtained in ex vivo and in vivo assays (Table 2). Additionally, the observed in vitro activity should be in the lower µM range (or higher), which is high

Towards allosteric receptors – synthesis of β-cyclodextrin-functionalised 2,2’-bipyridines and their metal complexes

• Christopher Kremer,
• Gregor Schnakenburg and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 814–824, doi:10.3762/bjoc.10.77

• processes. Multivalent [1][2] and cooperative binding [3][4][5] are two of the major concepts to ensure and control the efficiency in those events and the associated complex biochemical cascades following. In order to regulate several of their metabolical functions, a process named “allosteric regulation

Synthesis and biological activity of N-substituted-tetrahydro-γ-carbolines containing peptide residues

• Nadezhda V. Sokolova,
• Valentine G. Nenajdenko,
• Vladimir B. Sokolov,
• Daria V. Vinogradova,
• Elena F. Shevtsova,
• Ludmila G. Dubova and
• Sergey O. Bachurin

Beilstein J. Org. Chem. 2014, 10, 155–162, doi:10.3762/bjoc.10.13

• diseases [1][2][3]. Thus, one of the specific symptoms of such pathologies is a decrease in the ability of mitochondria to regulate the calcium homeostasis in cells and malfunction of mitochondrial permeability transition (MPT) that represents a key step in the cascades of cell death. From this point of

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• , XIAP, cAP2) in p53 status independent manner at nanomolar concentrations [30]. We have identified a new drimane sesquiterpene lactone, SF002-96-1, which inhibits survivin expression by interfering with critical signaling cascades (JAK/Stat, NF-κB) involved in transcriptional activation of the survivin

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

• , future studies of the scope and limitations of Lewis acid promoted Payne rearrangement–ring-opening cascades could establish their utility in organic synthesis. Lyconadin A. Retrosynthetic analysis of 1. Synthesis of triether 15. Synthesis and attempted ring-opening of epoxide 17. Attempted protection of

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• cascades yielded a diverse range of molecular scaffolds. The diversity of the products was increased through variation of all three of the building blocks used: the initiating, the propagating, and the terminating building block. The overall approach was facilitated by fluorous tagging of the initiating

Intramolecular carbolithiation cascades as a route to a highly strained carbocyclic framework: competition between 5-exo-trig ring closure and proton transfer

• William F. Bailey and
• Justin D. Fair

Beilstein J. Org. Chem. 2013, 9, 537–543, doi:10.3762/bjoc.9.59

• ’-tetramethylethylenediamine (TMEDA) to solutions of 3 in n-C5H12/Et2O (9:1 v/v) and subsequent warming of the reaction mixtures for various times at several different temperatures initiated the cascades. The results of these experiments are summarized in Scheme 4 and Table 1. Crude product mixtures were analyzed by capillary

Enantioselective total synthesis of (R)-(−)-complanine

• Krystal A. D. Kamanos and
• Jonathan M. Withey

Beilstein J. Org. Chem. 2012, 8, 1695–1699, doi:10.3762/bjoc.8.192

• from Eurythoe complanata in 2008, by Nakamura and Uemura [1]. Complanine induces inflammation by activating PKC (protein kinase C) in the presence of Ca2+ and TPA (12-O-tetradecanoylphorbol 13-acetate). PKC plays an important role in inflammation, namely through control of signal transduction cascades

• , and the biological activity of complanine may be understood in terms of controlling these cascades. From a structural perspective, complanine contains a novel trimethylammonium cationic group and can be characterized as possessing a homoconjugated all-Z-diene moiety and an amino alcohol N-acylated

Automated synthesis of sialylated oligosaccharides

• Davide Esposito,
• Mattan Hurevich,
• Bastien Castagner,
• Cheng-Chung Wang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 1601–1609, doi:10.3762/bjoc.8.183

• ; sialosides; Introduction Sialic acid (Sia) belongs to a family of nonulosonic acids, i.e., monosaccharides equipped with a carboxylic moiety and a nine-carbon backbone, which play a unique role in glycobiology. Sia-containing glycans mediate pathogen invasion [1] and are involved in signalling cascades

Multistep organic synthesis of modular photosystems

• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2012, 8, 897–904, doi:10.3762/bjoc.8.102

• experts only. As an example, we here focus in on the recent synthesis of multicomponent photosystems with antiparallel charge-transfer cascades in co-axial hole- and electron-transporting channels. The synthetic steps are described one-by-one, starting with commercial starting materials and moving on to

• fill them with functional π-stacks of free choice. Keywords: asparagusic acid; charge-transfer cascades; chromophores; disulfide exchange; hydrazone exchange; molecular switches; naphthalenediimides; π-stacks; surface-initiated polymerization; Introduction The architecture of photosystem 1 is rather

Volatile organic compounds produced by the phytopathogenic bacterium Xanthomonas campestris pv. vesicatoria 85-10

• Teresa Weise,
• Marco Kai,
• Anja Gummesson,
• Armin Troeger,
• Stephan von Reuß,
• Silvia Piepenborn,
• Francine Kosterka,
• Martin Sklorz,
• Ralf Zimmermann,
• Wittko Francke and
• Birgit Piechulla

Beilstein J. Org. Chem. 2012, 8, 579–596, doi:10.3762/bjoc.8.65

• ecological information is required. Most obviously it needs to be addressed as to whether X. c. pv. vesicatoria 85-10 emits volatiles while growing in the phyllosphere and whether the emission occurs continuously. Continuous volatile perception by the plant may be a prerequisite to induce signal cascades in

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• diastereoisomers in good yields (82% and 75%) when nitro-Mannich/lactamisation cascades were carried out with formaldehyde (3a) and butylamine (4c) or hept-5-yn-1-amine (4d), respectively. To extend the cascade methodology to the potential construction of architecturally complex piperidine-ring-containing