Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• (Scheme 6). The erythrina alkaloids are known to exhibit sedative, hypotensive and neuromuscular activity. This alkaloid skeleton consists of a tetracyclic spiroamine framework and synthetic chemists consider it as a challenging target. Simpkins and co-workers [11] have used the RRM sequence tactically to

• -1-ol (288) under optimized reaction conditions (MW, toluene, 80 °C) and the expected tandem metathesis product 289b was obtained along with the ROM–RCM product 289a. These compounds are useful synthones for the alkaloids synthesis (Scheme 61). In another instance, they also studied the efficiency of

• this method by isolating the RCM product of the ROM–CM byproduct 290, which was recovered in the ROM–RCM–CM cascade (Scheme 62). Kouklovsky and co-workers [62] have described a stereoselective synthesis of 2-(2-hydroxyalkyl)piperidine alkaloids by employing a RRM of NDA adduct 293. The required

Fe(II)/Et₃N-Relay-catalyzed domino reaction of isoxazoles with imidazolium salts in the synthesis of methyl 4-imidazolylpyrrole-2-carboxylates, its ylide and betaine derivatives

• Ekaterina E. Galenko,
• Olesya A. Tomashenko,
• Alexander F. Khlebnikov,
• Mikhail S. Novikov and
• Taras L. Panikorovskii

Beilstein J. Org. Chem. 2015, 11, 1732–1740, doi:10.3762/bjoc.11.189

• reaction with sulfur affording the corresponding imidazolethiones under very mild conditions. Keywords: imidazole; isoxazole; NHC carbene; pyrrole-2-carboxylate; relay catalysis; Introduction Pyrrole-2-carboxyate and imidazole units are present in bioactive pyrrole-imidazole alkaloids and pyrrole

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• , confirming its antimicrobial activity. The E-configuration of the chloroalkene moiety of indiacen B was confirmed by X-ray analysis. Keywords: biological evaluation; heterocycles; indoles; natural products; total synthesis; Introduction Indole alkaloids prenylated at the benzene ring are found in tropical

• -methylbuta-1,3-dien-1-yl)indole [7]. All enamine positions of the indole units are unsubstituted. As part of our program on the total synthesis of prenylated indole alkaloids [8][9][10][11], we considered it interesting to access indoles substituted only at the benzene ring and to conduct initial studies on

• product indiacen B (2), which was synthesized for the first time, was confirmed by X-ray analysis. The antimicrobial activity of synthetic indiacen B (2) was in the same range as that originally determined for the isolated natural product. Prenylated indole alkaloids raputindole A from the rutaceous tree

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

• on pyridoacridine-related metabolites as one biologically interesting group of alkaloids identified from marine sources. They are produced by marine sponges, ascidians and tunicates, and they are structurally comprised of four to eight fused rings including heterocycles. Acridine, acridone

• reported, pyridoacridine 13C NMR data. Observations have been made on the delocalization of electrons and the presence of some functional groups that lead to changes in the chemical shift of some carbon resonances. The lack of mass spectra information for these alkaloids due to the compactness of their

• structures is further discussed. Moreover, the biosynthetic pathways of some of these metabolites have been shown since they could inspire biomimetic synthesis. The synthesis routes used to prepare members of these marine alkaloids (as well as their analogues), which are synthesized for biological purposes

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

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

• release of torsional strain when the sp2 center in the six-membered ring is attacked, cyclohexanone represents a special case as this cyclic ketone is nearly as reactive as an aldehyde [24]. The resultant tetrasubstituted (red) cyclohexylamine is found in natural alkaloids such as (–)-lycodine (Figure 2

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

• Heck coupling: In 2003, Snieckus and co-workers [97] have synthesized the seco-C/D ring analogues of ergot alkaloids through the intramolecular Heck reaction as a key step. The coupling precursors 63 and 68 were prepared from 4-bromoindoles by a sequential Vilsmeier–Haack, Henry nitroaldol condensation

Hybrid macrocycle formation and spiro annulation on cis-syn-cis-tricyclo[6.3.0.0^2,6]undeca-3,11-dione and its congeners via ring-closing metathesis

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Rashid Ali

Beilstein J. Org. Chem. 2015, 11, 1123–1128, doi:10.3762/bjoc.11.126

• ][12][13][14][15][16][17][18][19][20][21]. Several approaches are available for the synthesis of carbocyclic quinanes, however, only a limited number of methods is available for oxa- [22][23][24][25] and aza-polyquinanes [26][27][28]. The indole unit is present in a variety of plant alkaloids (e.g

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• , University of Pardubice, Studentská 573, CZ 532 10, Pardubice, Czech Republic 10.3762/bjoc.11.99 Abstract 2-Aroylmethylidene-1,2,3,4-tetrahydroquinolines with the appropriate substituents can be suitable precursors for the synthesis of alkaloids from Galipea officinalis (cuspareine, galipeine, galipinine

• used in folk medicine for stimulation in the cure of some paralytic diseases [1] and for the treatment of fever [2]. In addition, antituberculous [3], antiplasmodial and cytotoxic [2] properties have been also described. The active constituents of the bark are mainly tetrahydroquinoline alkaloids such

• as galipinine, galipeine, cuspareine and angustureine (Figure 1) [1][4]. The synthesis of these alkaloids has attracted great interest in organic chemists and many procedures have been published to date [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• stereocontrolled approach has been developed for the syntheses of tashiromine and epitashiromine alkaloids from cyclooctene β-amino acids. The synthetic concept is based on the azetidinone opening of a bicyclic β-lactam, followed by oxidative ring opening through ring C–C double bond and reductive ring-closure

• reactions of the cis- or trans-cyclooctene β-amino acids. Keywords: alkaloids; amino acids; ring closure; ring opening; stereocontrolled synthesis; Introduction Indolizidine alkaloids are an important class of naturally occurring compounds which have received considerable attention as a result of their

• pyrrolizidine alkaloids [45]. Results and Discussion We describe here a novel access route for the synthesis of tashiromine and epitashiromine by starting from an unsaturated bicyclic β-lactam. The retrosynthetic concept of the synthesis is represented on Scheme 1 and was based on the lactam ring opening, in

Direct access to pyrido/pyrrolo[2,1-b]quinazolin-9(1H)-ones through silver-mediated intramolecular alkyne hydroamination reactions

• Hengshuai Wang,
• Shengchao Jiao,
• Kerong Chen,
• Xu Zhang,
• Linxiang Zhao,
• Dan Liu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 416–424, doi:10.3762/bjoc.11.47

• phytochemicals. They were extracted from a variety of plant families. Among the quinazolinone derivatives, such as the pyrrolo[2,1-b]quinazolinone alkaloids, are a multitude of biomedically active substances [1][2]. For example, deoxyvasicione (1), 8-hydroxydeoxyvasicinone (2), compound 73/602 (3

• through silver-catalyzed intramolecular hydroamination from readily available starting materials with a long-chain alkyne [35][36]. Motivated by the unique structural properties and the biological activities characteristic of the vasicinone type alkaloids, we extended our work in this direction by

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

• elements of secondary plant products. The quinoline skeleton is present in alkaloids derived from tryptophane-like quinine or camptothecine, whereas alkylated phenols with a varying alkyl side chain length are common metabolites from the shikimate pathway. Qsps were reported in a recent patent [50] to be

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• - and RNA-fluorescent markers (ethidium bromide), probes for cell viability (propidium iodide), but also “ill-famed” for various toxic (genotoxic) and mutagenic effects. After two decades of low interest, the discovery of phenanthridine alkaloids and new studies of antiparasitic/antitumor properties of

• . 5.5–6) yielding reversible positive charge. Here are also described novel approaches to reversible positively charged (DPP and DIP derivatives [45]), which are related to remarkable structural features of the naturally occurring benzophenanthridine alkaloids – pH-dependent structural transition

• various DNA and RNA were not studied in detail. One of several reasons for the increased research on phenanthridines is the discovery of naturally occurring analogues, e.g., some protoberberine alkaloids (Figure 12, sanguinarine and chelerythrine), widely distributed in several botanical families

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• -step of the synthesis of glycozoline 37, an antifungal and antibacterial agent. Analogously, 38 was converted to 39 as a part of the multistep synthesis of two different tetrahydropyrroloiminoquinone alkaloids 40 and 41 (Scheme 15) [58][60]. Tanaka et al. could achieve the electrochemical construction

• ). Electrosynthesis of 39 as part of the total synthesis of alkaloids 40 and 41. Wacker-type cyclization of alkenyl phenols 42. Cathodic synthesis of indol derivatives. Fluoride mediated anodic cyclization of α-(phenylthio)acetamides. Synthesis of 2-substituted benzoxazoles from Schiff bases. Synthesis of euglobal

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• . This publication highlights recent methods for setting quaternary and tetrasubstituted tertiary carbon stereocenters to address the synthetic hurdles encountered over many decades across multiple compound classes spanning carbohydrate derivatives, terpenes, and alkaloids. These enantioselective methods

• synthesis. This formal synthesis shows the power of the enantioselective allylic alkylation to access formerly racemic constructs as single enantiomers; Danishefsky’s synthesis is now rendered enantioselective. D) Aspidospermine The aspidosperma alkaloids have garnered much attention as beautiful targets

• for the synthetic chemist. Most of the 250-plus compounds in this class share a pentacyclic core, from the clinical anticancer therapeutics vincristine and vinblastine to the simpler aspidospermidine [60]. To address the challenging synthetic features of the aspidosperma alkaloids, many clever

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• aromatic ketones, using chiral alkaloids [96][97][98]. The most important semi-industrial scale electrocarboxylation processes are related to the synthesis of these NSAIDs. The α-hydroxy acid is an intermediate, still requiring a chemical hydrogenation to obtain the desired product. 2-Acetyl-6

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• material, the bridged tetracyclic framework of the Alstonia class of indole alkaloids was readily formed in high yield. This asymmetric [4 + 2] annulation was a seminal advance in the area of nucleophilic phosphine catalysis, attracting much attention toward chiral phosphine-catalyzed asymmetric reactions

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• analogs. Keywords: cyclopamine; C–H-functionalization; hedgehog signaling pathway; natural products; steroidal alkaloids; Introduction The isolation of cyclopamine (1, Figure 1) nearly 50 years ago followed by the determination of its biological target and pharmacological profile has drawn considerable

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• polyketides, nonribosomal peptides, terpenoids, alkaloids, lipids and others. Such compounds became a major source of biologically active natural products as antibiotics, cytotoxic compounds, immunosuppressants etc. In addition, actinomycetes are also able to produce and release a wide variety of volatile

• [2] such as methyl pyrrole-2-carboxylate, emitted by Stackebrandtia nassauensis, or 2-acetylpyrrole from Saccharopolyspora erythraea, volatile alkaloids are rarely produced by actinomycetes. We became interested in the strain Streptomyces sp. FORM5 to elucidate whether volatile formation is linked to

• ); HREIMS m/z: calcd for C10H13N, 145.0892; found, 145.0912; GC (BPX-5) I = 1368. Alkaloids produced by Streptomyces strain FORM5. Part of the total ion chromatogram of the headspace extract of Streptomyces sp. FORM5 with the structures of 2-propylpyridine (6), 2-pentylpyridine (7), (E)-2-(pent-3-en-1-yl

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• smenochromene D [21], pseudopteranes, furanocembranes [22], indole alkaloids [23], and antitumor cembrane lactones crassin and isolobophytolide [24][25]. Obviously, there is a need for P450s with changed chemoselectivity. Previously a systematic analysis of 31 P450 crystal structures and more than 6300 P450

Visible-light photoredox catalyzed synthesis of pyrroloisoquinolines via organocatalytic oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade with Rose Bengal

• Carlos Vila,
• Jonathan Lau and
• Magnus Rueping

Beilstein J. Org. Chem. 2014, 10, 1233–1238, doi:10.3762/bjoc.10.122

• Carlos Vila Jonathan Lau Magnus Rueping Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany 10.3762/bjoc.10.122 Abstract Pyrrolo[2,1-a]isoquinoline alkaloids have been prepared via a visible light photoredox catalyzed oxidation/[3 + 2] cycloaddition

• /oxidative aromatization cascade using Rose Bengal as an organo-photocatalyst. A variety of pyrroloisoquinolines have been obtained in good yields under mild and metal-free reaction conditions. Keywords: alkaloids; [3 + 2] cycloaddition; organocatalysis; oxidation; photochemistry; photoredox catalysis; Rose

• Bengal; visible-light; Introduction Pyrrolo[2,1-a]isoquinolines constitute the core structure of the natural products family lamellarin alkaloids (Figure 1) [1][2][3][4]. These alkaloids display numerous biological activities such as inhibitor of human topoisomerase I by lamellarin D [5] or inhibition

Visible light mediated intermolecular [3 + 2] annulation of cyclopropylanilines with alkynes

• Theresa H. Nguyen,
• Soumitra Maity and
• Nan Zheng

Beilstein J. Org. Chem. 2014, 10, 975–980, doi:10.3762/bjoc.10.96

• annulation. Fused indolines are common structural motifs that appear in a number of biologically active alkaloids and pharmaceuticals [37][38]. The [3 + 2] annulation of monocyclic cyclopropylanilines with alkynes provides a fast entry to this motif (Scheme 1). Starting from commercially available 1-bromo-2

Addition of H-phosphonates to quinine-derived carbonyl compounds. An unexpected C9 phosphonate–phosphate rearrangement and tandem intramolecular piperidine elimination

• Łukasz Górecki,
• Artur Mucha and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 883–889, doi:10.3762/bjoc.10.85

• ; Introduction Medicinal, organocatalytic and stereoselective properties of quinine make it the most prominent representative of Cinchona alkaloids [1], a group of natural compounds of a unique three-dimensional structure. The structure involves a particular arrangement of two rigid heterocyclic fragments

• novel contribution to the reactivity of quinine although similar eliminations of piperidine in Cinchona alkaloids have been reported in the literature. Accordingly, heating of quinine or derivatives in acids provided either quino-/cinchotoxine ketones or their tautomeric enol esters, depending on the

• stereoselective properties of the alkaloids [44][45]. An elimination associated with the phosphonate–phosphate rearrangement was also reported for other 1-hydroxyphosphonate systems [46][47][48]. Conclusion An intriguing chemical behavior of C-9 quinine-derived ketones was demonstrated in the Abramov (phospha

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• ] and anticancer [5] activities. The bioactive β-carboline alkaloids canthinone [6] and vinpocitine [7] also bear these substructures. Vinpocetine is a dehydrated derivative of the natural alkaloid of vincamine [8]. It is reported to have cerebral blood-flow enhancing [7] and neuroprotective effects [9

• ], and is used as a drug in Eastern Europe for the treatment of cerebrovascular disorders and age-related memory impairment [10]. We are interested in the isoindolo[2,1-a]quinoline skeleton (Figure 1) due to its structural similarities with these alkaloids. The most common method of synthesizing

Chromatographically separable rotamers of an unhindered amide

• Mario Geffe,
• Lars Andernach,
• Oliver Trapp and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 701–706, doi:10.3762/bjoc.10.63

• .10.63 Abstract Surprisingly stable formamide rotamers were encountered in the tetrahydroisoquinoline and morphinan series of alkaloids. We investigated the hindered rotation around the amide bond by dynamic high-performance liquid chromatography (DHPLC) and kinetic measurements of the interconversion of

• for the syntheses of various isoquinoline alkaloids [5][6][7]. Spontaneous dehydrocyanation afforded the 1-benzylated 3,4-dihydroisoquinoline which was subsequently reduced in situ to tetrahydroisoquinoline 3 in a one-pot procedure with sodium borohydride in 63% yield. N-Acylation was effected