Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• was much lower (2.6:1 and 1:1, respectively). Acid hydrolysis of 64 gave (4S)-4-hydroxy-L-glutamic acid [(2S,4S)-3] as the hydrochloride, however, its enantiomeric purity was not checked. In connection with the total synthesis of thiopeptide antibiotic nosiheptide an orthogonally protected (4S)-4

• orthogonally protected (2S,4S)-4-hydroxyglutamic acid 85 as an intermediate in the total synthesis of antibiotic nosiheptide [83][84] employs the N-Boc derivative of natural (2S,4R)-4-hydroxyproline 82 as a starting material (Scheme 21) [84][85]. The inversion of configuration at C4 was carried out by

• precursor in the total synthesis of longicatenamycin A [25]. Syntheses of several modified cephems started from dimethyl (2S,4R)-N-Boc-4-hydroxyglutamate (81) [114]. Protected 4-hydroxyglutamic acids (2S,4S)-66 [75][76] and (2S,4S)-85a [84][85] after installation of the thiazole ring at the C1 terminus were

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• pentasaccharide chain [5][6]. The pioneering work by Paulsen was later followed up by a total synthesis by the Ogawa group [7] and an oligosaccharide synthesis by the Magnusson group [8]. With the increasing understanding of glycobiology, the Forssman antigen has remained an interesting target for vaccine

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

• potent antibacterial activity against Helicobacter pylori and induce growth defects in Escherichia coli and Staphylococcus aureus. Taking inspiration from a methodology used in our total synthesis of natural products, we applied this methodology to access analogues possessing bulky N-substituents

• proposed that this development should be limited under certain conditions [7]. We wished to investigate the potential of 1–8 to modulate QS in P. aeruginosa, however, the compounds are available in only trace amounts from natural sources [3], and so we embarked on the total synthesis of the compounds. We

• flash column chromatography, which may account for the slightly lower yields in these cases (13ad and 13ae). With the compounds 13 now in hand, their cyclisation to the desired analogues 14 was explored. However, whilst the conditions which had proved successful in the total synthesis of natural

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• application as advanced intermediates in the total synthesis of Lycopodium alkaloids [3][4][5][6], 3a-substituted 2,4-dicarbonyl compounds being particularly useful in this field. The synthetic approaches toward these versatile building blocks (i.e., compounds with the functionalization pattern A) are

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• (Figure 2b). We have been exploring the utility of hydrophobic B12 model complexes, such as heptamethyl cobyrinate perchlorate 1, that possess ester groups in place of the peripheral seven-amide moieties [28][29]. 1 was developed by Eschenmoser et al. as a model complex for the total synthesis of vitamin

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• , as they possess biologically validated structures, which could become suitable leads in drug discovery [2]. Recently, our research group reported the first total synthesis of leopolic acid A (Figure 1), a fungal metabolite from a terrestrial-derived Streptomyces sp. isolated from the rhizosphere of

• -pyrrolidinedione nucleus are quite rare [8][9][10][11]. The lack of similar compounds may be due to the instability of the 2,3 pyrrolidinedione moiety [12]. Indeed, while developing the total synthesis of leopolic acid A, we encountered several difficulties in the construction of the ring, most of the

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• carbinols afforded novel allene systems. Our study may be of help towards the total synthesis of solenopodin or klysimplexin derivatives. Keywords: conformational analysis; low valent titanium; marine natural products; pinacol coupling; ten-membered rings; Introduction Eunicellane-type diterpenoids share

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

• triphenylsiloxide ligands (type II) introduced by A. Fürstner and co–workers is frequently used in the total synthesis of natural products [23][24][25][26][27]. A unique catalytic reactivity towards conjugated diynes was observed for the tungsten benzylidyne complex with OSi(Ot-Bu)3 ligands (type III) [28][29][30

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

• 10.3762/bjoc.14.206 Abstract The stereoselective total synthesis of strongylodiol H and I has been accomplished. The synthetic procedure comprised the stereoselective reduction of a ketone functionality in an ene–yne–one employing CBS as a catalyst and a Cadiot–Chodkiewicz coupling reaction as the key

• concentrations [11]. There have been few contributions on the total synthesis of strongylodiols [12][13] employing alkynylation of an unsaturated aliphatic aldehyde catalyzed by Trost’s pro-phenol ligand [12][14], β-elimination of epoxy chloride [15], Noyori’s asymmetric reduction of ynones [16], diyne addition

• have accomplished the total synthesis of the diacetylenic polyol natural products petrosiols A, D, E (11,12,13) [22][23] and strongylodiols A–D (1–4) [24]. Herein we describe the total synthesis of strongylodiols H and I (9 and 10). Results and Discussion Retrosynthesis for strongylodiol H and

Studies towards the synthesis of hyperireflexolide A

• G. Hari Mangeswara Rao

Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185

• cyclopentane 5, a functionalized key intermediate, is presented. Compound 5 is involved in hydrolysis, α-allylation at C-8 and α-methylation at C-10 stereoselectively from the convex face. Then it is subjected to cross metathesis to give α,β-unsaturated ketone 11 as precursor in the total synthesis of

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• the desired biologic effect in living organisms, while the other enantiomer could be inactive, cause whole other biological responses or might even have the opposite effect. Hence, for the total synthesis of natural products or pharmaceuticals it is crucial to generate chirality with high

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• integration of experimental conditions with smaller laboratory footprint. In addition to the most obvious purpose of having such a platform that will facilitate the synthesis of any molecule including several intermediate stages, it will help in terms of the following: End-to-end synthesis: Total synthesis 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

• synthesis In 2005, Wipf and Spencer [79] reported the first total synthesis of the Stemona alkaloid (−)-tuberostemonine (40). In this report, PIDA (15) was used as an electrophile for the synthesis of spirolactone 16 in 35% yield by the cyclization of L-tyrosine 14 in nitromethane at room temperature for

• of ortho-spirocarbocyclic compounds which is broadly found to originate in most of bioactive natural products [111][112]. 4.3. Application of spirocarbocyclic compounds in natural product synthesis In 2003, Kita and co-workers [113][114] employed a iodine(III) reagent during the total synthesis of

• discorhabdin A (112). In 2006, Honda and co-workers [115] reported the total synthesis of spiro-isoquinoline alkaloid (±)-annosqualine (1). In this report, the substrate 113 was cyclized to form spirocyclic compound 114 via desilylation with TBAF in THF followed by reaction with n-BuLi in hexafluoroisopropanol

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• otherwise difficult to synthesize β-mannosides using the Mitsunobu procedure. This approach to 1,2-cis-mannosides is equally effective when cyclohexylidene protecting groups are used [28][47][62]. Mitsunobu glycosylation was also a successful method in total synthesis. In the course of a 17-step synthesis

•  15) [63]. Similar reaction conditions were applied by Nie et al. in the total synthesis of the nucleoside antibiotic A201A [64]. Notably, the n-Bu3P-ADDP reagent system led here to the formation of the pure α-glycoside. Likewise, a Mitsunobu glycosylation of complex phenols was successfully

• approach was recently adopted in a total synthesis of aurantoside G, involving the Mitsunobu ligation of a D-xylopyranose derivative 116 and N-nosylated methyl asparaginate 117 to give 118 (Scheme 22) [87]. Compared to N-sulfonylation, N-carbamoylation can also prove effective to enhance the acidity of a

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

• ) were obtained in the reaction of the N-benzyl 5-Br substituted substrate (R1 = 5-Br, R2 = Bn). Enantioselective Friedel–Crafts reactions The Friedel–Crafts reaction is widely employed in total synthesis [63][64][65]. In 2015, Pedro et al. reported the first asymmetric Friedel–Crafts reaction of N-Boc

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• [2][3]. Their high cytotoxicity prompted manifold studies that were initially focussed on the total synthesis and structure–activity relationships [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. This work resulted in the identification of cryptophycin-52, a highly biologically active

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• challenging and application-oriented conversions that can be applied for the total synthesis of natural products as well as in industry related to pharmaceutical and medicinal chemistry. These environmentally friendly, cheap and readily available reagents will surely attract the attention of scientists

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• ; oligosaccharides; stereoselectivity; total synthesis; Introduction Complex glycans serve as attractive targets for carbohydrate-based vaccines and therapeutics [1][2][3]. Streptococcus pneumonia (SPn) has been posing a serious threat in recent times. It is a major cause of pneumonia, bacteraemia, and meningitis

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• compounds. Wilson et al. successfully achieved the total synthesis of xyloketals 17 and 18, including cycloaddition of substituted dihydrofurans and 1-(2,4-dihydroxy-3-(morpholinomethyl)phenyl)ethanone via o-QM intermediates [69]. Osyanin et al. reported the synthesis of Uvaria scheffleri alkaloids

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

• Thaís A. Rossa,
• Nícolas S. Suveges,
• Marcus M. Sá,
• David Cantillo and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2018, 14, 506–514, doi:10.3762/bjoc.14.36

• the aziridine intermediate 3 was stable and could be isolated when the reaction was carried out in non-polar solvents. In particular, 2-(halomethyl)oxazoles 6 are a class of compounds rather underexplored, even though they are frequently key intermediates in the total synthesis of natural products [30

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• widespread use as activated donor substrates for endo-β-N-acetylglucosaminidase (ENGase) enzymes, an important application that has correspondingly stimulated interest in their production, both by total synthesis and by semi-synthesis using oligosaccharides isolated from natural sources. Amongst the many

• synthetic approaches reported, the majority rely on the fabrication (either by total synthesis, or semi-synthesis from locust bean gum) of a key Manβ(1–4)GlcNAc disaccharide, which can then be elaborated at the 3- and 6-positions of the mannose unit using standard glycosylation chemistry. Early approaches

• for any further protecting group manipulations, and simplifying synthetic strategies. As an alternative to total synthesis, significant quantities of several structurally complicated N-glycans can be isolated from natural sources, such as egg yolks and soy bean flour. Enzymatic transformations of

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

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

• based on the use of chiral substrates and enantioselective catalytic procedures. Keywords: asymmetric (aza)-Reformatsky reaction; asymmetric synthesis; chirality; diastereoselectivity; enantioselectivity; total synthesis; Introduction The Reformatsky reaction involves the formation of β

• enantioselective (aza)-variants by using chiral substrates or chiral ligands. As illustrated in this review, the diastereoselective Reformatsky reactions of chiral substrates or auxiliaries have been applied to the total synthesis of a number of important products, such as naturally occurring bioactive products

• to prepare these products. For example, this methodology was employed in 2014 by Kawanishi and Yamakoshi to develop the first total synthesis of naturally occurring prunustatin A, a novel inhibitor of glucose-regulated protein 78 expression [17]. As shown in Scheme 2, the key step of the synthesis

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• pharmaceutically useful chemicals. Further modification of this chloramphenicol scaffold as well as total synthesis of other natural chemicals are right now ongoing in our lab. Experimental General procedure for the synthesis of 9 Similarly as described in [37], with stirring under an atmosphere of nitrogen

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

• products and in drug development and hence, effective synthetic approaches are required. Here we present a novel method for the introduction of a methyl group at C1 of isoquinolines. This is exemplified by a new total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline. Direct metalation of

• derivative 5 in reasonable yield. Later on, hydrogenolytic cleavage of the generated benzylamine-type group at C1 should give the desired 1-methyl moiety. Related reductive cleavage reactions have been published earlier by Möhrle [20] for phenolic Mannich bases in the course of the total synthesis of the

• . In this manner alkaloid 1 was obtained in 94% yield (18% overall yield from commercially available precursor 2, Scheme 2). Conclusion In conclusion, we have worked out two novel protocols for the introduction of a methyl group at C1 of isoquinolines. These were applied to the total synthesis of the

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

• dimer was assigned as being trans, by X-ray crystallographic analysis. The kinetic reaction profile was determined by using 1H NMR reaction monitoring and revealed a second order overall kinetic profile. Furthermore, by employing this methodology, a diastereoselective total synthesis of a functionalized