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

• particular focus on recent developments in this methodology and its use in total synthesis. Keywords: carbon–carbon bond formation; Michael addition; nitrosoalkenes; oximes; total synthesis; Introduction Conjugated nitrosoalkenes (NSA) are close analogs of α-nitroalkenes, which are important Michael

• , Michael addition of C-nucleophiles to α-nitrosoalkenes opens access to synthetically valuable α-branched oximes, which can be further utilized as useful intermediates in total synthesis. The high potential of this carbon–carbon bond-forming strategy has been recognized since 1970s in works of Corey

• nucleophile as well as asymmetric catalysis still remains to be studied in these reactions. The high efficiency and stereoselectivity of the enolate addition to nitrosoalkenes make this strategy perspective for application in total synthesis that has been recognized since 1970s. Thus, Oppolzer and co-workers

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• ][11][12][13][14][15][16][17][18][19][20], which continue to remain in the focus of attention for many research groups worldwide as targets for total synthesis and to serve as inspiration for exercises in drug design. Although many preparative methods of assembly of these structural units have been

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• was then subjected to another round of Tf2O-mediated glycosylation leading to trisaccharide 20 in one pot (Scheme 5b). As compounds 16 and 20 have relatively simple structures, the scope of this 2-pyridyl glycosylation method will need to be established in the total synthesis of more complex

• /AgOTf (Scheme 17). This is presumably due to the inertness of the ditolyl disulfide side product from p-TolSCl/AgOTf promoted activation, which does not interfere with glycosylation. The p-TolSCl/AgOTf-promoted preactivation glycosylation has been successfully applied to the total synthesis of complex

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

• structure and fascinating biology, mycolactones have inspired various total synthesis endeavors and structure–activity relationship studies. Although this review intends to cover all synthesis efforts in the field, special emphasis is given to the comparison of conceptually different approaches and to the

• discussion of more recent contributions. Furthermore, a detailed discussion of molecular targets and structure–activity relationships is provided. Keywords: Buruli ulcer; mode of action; mycolactones; structure–activity relationships; target elucidation; total synthesis; Review I. Mycolactones and Buruli

• HPLC, neither of the isomers could be isolated in pure form, presumably due to rapid (re)equilibration during or after separation. Indeed, this presumption was later proven to be true by the (attempted) targeted total synthesis of each isomer; as part of this work, mycolactones A and B were shown to

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• acylation following Kunitomo’s strategy. Main advantage of this approach should be that the laborious introduction of the carboxy residue at a late stage of the total synthesis is circumvented. Alternatively, quenching of the 1-magnesiated alkoxyisoquinolines with iodine should lead to 1-iodoisoquinolines

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• structure and the suggested stereochemistry. The synthesis was based on a new strategy which includes an efficient access to the 15-guanidino-3-hydroxypentadecanoyl (GHPD) side chain from erucamide. Keywords: cyclodepsipeptides; fusaricidins; lipopeptides; structure elucidation; total synthesis

• allylation with BINOL-titanium catalysts failed due to low conversion [14]; however, in spite of good experience with the Maruoka–Keck allylation in another total synthesis, the conversion was not satisfying in this case [15]. After protection and guanidinylation with triflylguanidine 14, the homoallylic

• was performed with extensive NMR spectroscopy and tandem mass spectrometry. The full stereostructure of the major component, fusaricidin E, could be confirmed by total synthesis. It included a macrolactamization approach combined with a late stage attachment of the GHPD side chain which was

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• -series LFF571 developed by Novartis is currently evaluated for treating Clostridium difficile intestinal infections [10]. Due to their important biological activity, many groups such as Moody, Bagley, Bach, Nicolaou, Hashimoto–Nakata, Ciufolini and Alvarez are actively involved in the total synthesis of

• the neat synthesis of GE2270 central core in 33% yield over a 4-step sequence (Figure 1) including three Negishi and Stille cross-coupling reactions to achieve the direct introduction of mono- and dithiazolyl units to a 2,3,6-trihalopyridine [17]. The strategy has then extended to the total synthesis

Biomimetic molecular design tools that learn, evolve, and adapt

• David A Winkler

Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125

• learning matches that of humans) by between 2029 and 2045 are not so unrealistic. Hypothesized evolution of ‘life’ and ‘intelligence’. Structure of maitotoxin, one of the most complex natural products ever tackled by total synthesis. Reprinted with permission from [3]; copyright 2014 American Chemical

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• bacterium Chitinophaga sancti. They show antibacterial activity against Gram-positive bacteria. A second generation total synthesis of the antibiotic elansolid B1 (2) and the first synthesis of elansolid B2 (3) are reported. In contrast to previous work, the (Z,E,Z)-triene at C10–C15 was assembled by using

• an optimized C–C cross-coupling sequence with a Suzuki cross-coupling reaction as key step. Keywords: antibiotics; polyenes; polyketides; Stille reaction; Suzuki reaction; total synthesis; Introduction The elansolids are metabolites from the gliding bacterium Chitinophaga sancti (formerly

• elansolids B1 (2) and B2 (3) along with A3 (4) bearing the unusual p-quinone methide unit were isolated from the fermentation broth. All elansolids belong to the group of trans-polyketides type I [3][4][5][6]. For the first generation total synthesis of elansolid B1 (2) we utilized an endo-selective

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• ]. 5.1.2 Esterification of benzoic acids with glycosyl donors: Again in 2015 Kawabata and co-workers applied the Mitsunobu reaction to an unprotected and unactivated donor in the first step of the total synthesis of two ellagitannins. Using a moderate excess

Phosphorus pentasulfide mediated conversion of organic thiocyanates to thiols

• Chandra Kant Maurya,
• Avik Mazumder and
• Pradeep Kumar Gupta

Beilstein J. Org. Chem. 2017, 13, 1184–1188, doi:10.3762/bjoc.13.117

• reducing agents, as required by the reported methods. In this way, this method presents an attractive method for the preparation of thiols which, in addition, can be useful for the generation of a thiol functional group during a total synthesis. Experimental General experimental procedure: In a three-neck

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

• total synthesis of vital importance for the further preclinical development. This review describes in detail the various tactics and strategies employed so far in archazolid syntheses that culminated in three total syntheses and discusses the future synthetic challenges that have to be addressed

• . Keywords: anticancer agent; medicinal chemistry polyketides; synthetic methodology; total synthesis; Introduction The complex structures of polyketides continues to be a great challenge for synthetic chemists and has also been a key driver for the development of new methodologies [1][2][3][4][5][6][7][8

• ][9]. In many cases, total synthesis is of critical importance to enhance the supply of these often scarce metabolites and even complex polyketides have been prepared on an industrial scale [10][11]. These natural products are also valuable molecular probes for the discovery and evaluation of novel

Total synthesis of TMG-chitotriomycin based on an automated electrochemical assembly of a disaccharide building block

• Yuta Isoda,
• Norihiko Sasaki,
• Kei Kitamura,
• Shuji Takahashi,
• Sujit Manmode,
• Naoko Takeda-Okuda,
• Jun-ichi Tamura,
• Toshiki Nokami and
• Toshiyuki Itoh

Beilstein J. Org. Chem. 2017, 13, 919–924, doi:10.3762/bjoc.13.93

• Environment, Faculty of Regional Sciences, Tottori University, 4-101 Koyama-minami, Tottori 680-8551, Japan Center for Research on Green Sustainable Chemistry, Faculty of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan 10.3762/bjoc.13.93 Abstract The total synthesis of TMG

• electrochemical solution-phase synthesis developed by us. The synthesis of structurally well-defined TMG-chitotriomycin has been accomplished in 10-steps from a disaccharide building block. Keywords: automated synthesis; electrochemical oxidation; glycosylation; glucosamine; total synthesis; Introduction

• synthesis was completed by Yu [8][9]. Although the activity of TMG-chitotriomycin (1) was moderate, it selectively inhibits glucosaminidases derived from insects and fungi. Therefore, TMG-chitotriomycin (1) has a potential as a lead compound for safe insecticides and pesticides. Recently, the total

First total synthesis of kipukasin A

• Chuang Li,
• Haixin Ding,
• Zhizhong Ruan,
• Yirong Zhou and
• Qiang Xiao

Beilstein J. Org. Chem. 2017, 13, 855–862, doi:10.3762/bjoc.13.86

• Chuang Li Haixin Ding Zhizhong Ruan Yirong Zhou Qiang Xiao Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science & Technology Normal University, Nanchang, Jiangxi 330013, China 10.3762/bjoc.13.86 Abstract In this paper, a practical approach for the total synthesis of kipukasin A is

• subsequent Vorbrüggen glycosylation, the protecting group could be removed smoothly in the presence of 5 mol % Ph3PAuOTf in dichloromethane to provide kipukasin A in high yield and regioselectivity. Keywords: gold catalysis; kipukasin A; marine nucleoside; total synthesis; Vorbrüggen glycosylation

• studies of marine nucleosides, total syntheses of several marine nucleosides were accomplished in our group [14][15][16][17][18]. In the present paper, we reported a practical approach for the total synthesis of kipukasin A. Results and Discussion From the synthetic point of view, it seemed that the most

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• alternative for the delivery of simpler isoprenoid structures such as carotenoids [12]. Industrially relevant total synthesis of highly oxygenated terpenes comprising several chiral centers is often more complex since usually various different reaction steps have to be performed that regularly involve cost

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

• . Nakiterpiosin (117) is a marine sponge metabolite which demonstrates a potent cytotoxicity against the P388 leukemic cell line. The photo-variant of the Nazarov cyclization has been applied as one of the steps in the total synthesis of nakiterpiosin (117, Scheme 37) [63]. Starting from substrate 115, 1-indanone

• , potentially more selective than known compounds [87]. Transformation of diazo compounds 209 into 1-indanone derivatives 210, catalyzed by rhodium acetate, has been one of the steps in the total synthesis of atipamezole analogues 211 (Scheme 58). The most common symptom of the menopause is hot flash, which is

(Z)-Selective Takai olefination of salicylaldehydes

• Stephen M. Geddis,
• Caroline E. Hagerman,
• Warren R. J. D. Galloway,
• Hannah F. Sore,
• Jonathan M. Goodman and
• David R. Spring

Beilstein J. Org. Chem. 2017, 13, 323–328, doi:10.3762/bjoc.13.35

• , particularly in the field of total synthesis where it is often used to install vinyl iodides with high levels of geometric purity which can then be utilised in metal-catalysed cross-coupling reactions [2][6]. Hodgson et al. [7] and later Takai et al. [5] have proposed very similar models to explain the (E

• total synthesis programme, we subjected 6-chlorosalicylaldehyde (6) to standard Takai olefination conditions using iodoform (see Supporting Information File 1 for details) to form alkenyl iodide product 7 (Scheme 3). To our surprise a large excess of the (Z)-isomer of 7 relative to the corresponding (E

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• (15i–k). A series of aliphatic α-iminonitriles also gave good results (15n,o). Notably the labile dimethylacetal group tolerates this two-step transformation (15m). Using this protocol, the authors described a total synthesis of (±)-isoretronecanol (19), a pyrrolizidine alkaloid (Scheme 9). In this

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• better immunological understanding of the epitopes that protect from bacterial infection requires defined oligosaccharides obtained by total synthesis. The key to the synthesis of the S. pneumoniae serotype 12F CPS hexasaccharide repeating unit that is not contained in currently used glycoconjugate

• ] strategy that was not successful due to steric constraints. The synthetic hexasaccharide is the starting point for further immunological investigations. Keywords: carbohydrate antigen; glycosylation; oligosaccharides; Streptococcus pneumoniae; total synthesis; Introduction Streptococcus pneumoniae is a

• disaccharide branch at C3 of β-D-ManpNAcA and C3 of α-L-FucpNAc [15]. We established a total synthesis of the hexasaccharide repeat unit as a first step toward a detailed immunological analysis of S. pneumoniae 12F. Results and Discussion Retrosynthetic analysis. Initially, a convergent [3 + 3] synthesis of

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• ) this includes three and four crosslinks, respectively, which occur between the side chains of aromatic residues [3] within the parent heptapeptide (Figure 1b) [4]. This degree of crosslinking in turn renders the total synthesis of GPAs as unfeasible for production and hence both first and second

Chromium(II)-catalyzed enantioselective arylation of ketones

• Gang Wang,
• Shutao Sun,
• Ying Mao,
• Zhiyu Xie and
• Lei Liu

Beilstein J. Org. Chem. 2016, 12, 2771–2775, doi:10.3762/bjoc.12.275

• group [26][27][28][29][30], and they established a toolbox approach to search for the specific ligand with a given substrate in the Cr-catalyzed process [28]. They successfully applied the method to the natural product total synthesis like halichondrin B and norhalichondrin B, and in the subsequent

Symmetry-based approach to oligostilbenoids: Rapid entry to viniferifuran, shoreaphenol, malibatol A, and diptoindonesin G

• Youngeun Jung,
• Dileep Kumar Singh and
• Ikyon Kim

Beilstein J. Org. Chem. 2016, 12, 2689–2693, doi:10.3762/bjoc.12.266

• in the literature [4][5][6][7][8][9][10]. In connection with our research on benzofurans [11][12], our laboratory has been involved in the synthesis of these benzofuran-containing natural products for the last several years [13][14][15]. For example, we have reported a concise total synthesis of

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• methanol/dichloromethane/ammonium hydroxide. The spectroscopic data compared well with previously published results [7]. In particular, 13C chemical shifts for both tashiromine and epitashiromine were within ±1.0 ppm of those reported by Dieter et al. [32] and Kim et al. [33]. Conclusion A concise total

• synthesis of (±)-tashiromine (1) and (±)-epitashiromine (2) using enaminone chemistry is reported. The NMR spectroscopic data correlated well with those in previously reported syntheses. The synthetic approach indicated that there was reasonable tolerance of functionality at the 8-position, with only the

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• revised from S to R, upon total synthesis [33]. The mannopeptimycins contain a unique sugar substituted hydroxyenduracididine residue (blue, Figure 5). The mannopeptimycins displayed moderate activity against Gram-positive bacteria, including MRSA, but only exhibited weak activity against Gram-negative

• Minosaminomycin by Kondo et al.: The only total synthesis of minosaminomycin (9) to date was reported in 1977 by Kondo et al. (Scheme 14) [69]. Enduracididine (1) was prepared using the method reported by Shiba et al. [54] and was coupled with the isocyanate formed in situ from protected leucine 74 affording urea

• -isomer exhibited 80% lower bacteriostatic activity against Mycobacterium smegmatis ATCC 607 compared to the parent natural product. Synthesis of Mannopeptimycin aglycone by Doi et al.: In 2014, the total synthesis of the mannopeptimycin aglycone (77) was reported by Doi et al. [33]. The aglycone was

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug

• Wiesława Perlikowska,
• Remigiusz Żurawiński and
• Marian Mikołajczyk

Beilstein J. Org. Chem. 2016, 12, 2234–2239, doi:10.3762/bjoc.12.215

• atom and step economy. Since a detailed evaluation of the biological activity and preclinical studies requires gram quantities of each stereoisomer of 1, we sought a shorter and more efficient approach to our targets. Herein we disclose a new total synthesis of all enantiomerically pure rosaprostol

• preparation of rosaprostol stereoisomers 1a–d. Results and Discussion The total synthesis of stereoisomeric rosaprostols 1a–d commenced with the resolution of racemic 2-dimethoxyphosphoryl-3-hexylcyclopentan-1-one (3). Thus, a solution of (±)-3 in methylene chloride was reacted with (+)-(R)-1-(1-naphthyl

• formed in this reaction (not shown) were immediately hydrolyzed under basic conditions affording the two desired rosaprostol stereoisomers (−)-1b and (+)-1d in 71 and 68% yield, respectively. Finally, for the sake of completeness of our total synthesis of stereoisomeric rosaprostols 1, the p