Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by ¹H NMR spectroscopy

• Yoshihiro Nishida,
• Mengfei Yuan,
• Kazuo Fukuda,
• Kaito Fujisawa,
• Hirofumi Dohi and
• Hirotaka Uzawa

Beilstein J. Org. Chem. 2017, 13, 1999–2009, doi:10.3762/bjoc.13.196

• -glycerols, which play essential roles in the metabolism and anabolism of glycerolipids [25][26][27][28]. Compound 3 is prepared by the catalytic hydrogenolysis of benzyl ether 2 (for the synthetic details, see Supporting Information File 1). The 1H NMR spectrum of 3 in a CDCl3 solution (Figure 2a) shows a

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

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

• unstabilized THF [22] while stabilized THF was used in our case. Due to solubility problems in 1,4-dioxane and other solvents suitable for hydrogenolysis, the deprotection was thus performed in DMF [23][24]. Unfortunately, an O→N acyl shift to product 26 could be observed as judged by NMR spectroscopy when

• aged DMF was used for this purpose. In fresh DMF, hydrogenolysis smoothly produced amine 7 instead. When the crude peptide was coupled to the GHPD side chain unit 3, HPLC showed only a single peak with the correct m/z ratio. This compound 24 was isolated by preparative HPLC and NMR analysis showed a

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

• perfect stereoselectivity (Scheme 30). Glycosylation of the resulting DBT-β-glycosides was carried out in various alcohols (selected examples shown in Table 7) under Pd/C-catalyzed hydrogenolysis conditions to liberate the desired 1,2-cis glycoside and cyanuric acid. The reductant was either H2 (non

• -alkynyl acceptors) or Et3SiH (alkynyl acceptors). In all cases the yields were very good and the stereoselectivity pretty good for the 1,2-cis glycoside diastereomer. The mechanism is thought to proceed through an initial hydrogenolysis of the benzyl groups to produce a reactive dihydroxytriazinyl

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• similar system [22], the final hydrogenolysis of the Cbz protecting group with H2 and either Pd/C or Pd(OH)2 (up to 50 mol % catalyst loading) in EtOAc, MeOH or AcOH was attempted, but no trace of the desired lactone 9 was observed. A control experiment with the addition of tosyl chloride after the

• hydrogenolysis to form the known tosyl-protected intermediate 7 indicated no signs of product and therefore the CBz strategy was also abandoned. Second strategy without protecting group Since the protective group removal was problematic we decided to preinstall the desired N-substituent and thereby avoid any N

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• catalytic hydrogenolysis. The latter reaction simultaneously cleaves the benzyl and isopropylidene groups affording compound 2 as a single isomer [22]. In the case of 5-(2’-deoxy-2’-methyl-2’-fluoro-β-D-ribosyl)-1,2,3-triazole-4-carboxamide (3) the synthesis was more delicate as it is necessary to

• with tetrabutylammonium fluoride leading to the mixture of diols 17 and 18 in quantitative yield which were easily separated (Scheme 3). Finally, the aminolysis of compound 17 followed by catalytic hydrogenolysis in the presence of palladium chloride led to the desired compound 3 [22] (Scheme 4

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• be obtained on a multigram scale from the chiral pool. In order to obtain a series of new organocatalysts with substituents of different sizes and stereoelectronic properties in the dioxolane moiety, the following reaction sequence was applied to compounds 2 and 4: a) N-deprotection by hydrogenolysis

• and subsequent hydrogenolysis of the benzylcarbamate with molecular hydrogen in the presence of catalytic Pd/C (Scheme 5) afforded OC11 in 43% overall yield for the two steps. With this series of pyrrolidines at hand, the well-established Michael addition of aldehydes to nitroolefins [16][17][18] was

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• , may produce traces to significant amounts of side-products via hydrogenolysis. Thus, we decided to modify Panda’s synthetic route to significantly increase the overall yield. We hypothesized that this problem might be circumvented by performing the debenzylation reaction prior to the epoxide-ring

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

• -Benzylidene-1-indanones 126a–o were obtained by a Knoevenagel condensation of 1-indanone 125 with various aromatic aldehydes. Hydrogenolysis of 2-benzylidene-1-indanone 126b using Pd/C allowed to obtain 2-benzyl substituted 1-indanone 127 (Scheme 40). 2-Bromo-6-methoxy-3-phenyl-1-indanone 130, as an

• hydrogenolysis of the resulting double bond with Pd(OH)2/C, gave benzoic acid 213. Next, the latter was converted to α-diazo-β-keto ester 214 which then was submitted to the rhodium(II) acetate catalyzed intramolecular, carbon–hydrogen insertion reaction to give the spiroindane 215. Finally, the spiroindane 215

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• furnished the protected dipeptides 8a and 8b, respectively. Hydrogenolysis with hydrogen gas and palladium on charcoal gave free amines 9a and 9b. Glorin (1) and glorinamide 2 were then obtained by treating amines 9a and 9b, respectively, with propionic anhydride. The main advantage of our synthesis over

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

• employing a more nucleophilic and less basic reagent such as a lithium hydroxide/hydrogen peroxide mixture did not provide relief from the problem, but instead also produced a mixture of undesired products. Adjustments in the sequence of deprotection steps by first carrying out hydrogenolysis using Pd/C in

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• proceeded well and afforded the expected 5-(1,2,3-triazolyl)-substituted 1,2-oxazine syn-26 in moderate yield (54%). Hydrogenolysis belongs to the well-established transformations of 1,2-oxazines, often successfully leading to valuable compounds including 1,4-amino alcohols or pyrrolidine derivatives. We

• therefore briefly examined the reaction of 5-aryl-substituted 1,2-oxazines syn-21 and anti-24 under previously established conditions [53]. The hydrogenolysis of 1,2-oxazine derivative syn-21 in methanol using palladium on charcoal as catalyst afforded the expected α-(3-methoxyphenyl)-substituted γ-amino

• 95:5). In contrast, when these hydrogenolysis conditions were applied to the D-arabinose-derived 5-phenyl-1,2-oxazine anti-24 merely an inseparable complex mixture of products was obtained. After shortening of the reaction time from one day to one hour, we were able to isolate two products, the N

Regiocontroled Pd-catalysed C5-arylation of 3-substituted thiophene derivatives using a bromo-substituent as blocking group

• Mariem Brahim,
• Hamed Ben Ammar,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2016, 12, 2197–2203, doi:10.3762/bjoc.12.210

• -phenylthiophene (27) in 60% yield. A higher yield of 80% in 28 was obtained for the coupling of 16 with phenylboronic acid. In order to further demonstrate that a bromo-substituent at C2-position of the thiophenes can be considered as a protecting group, we removed it via palladium-catalysed hydrogenolysis

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• (6) (Scheme 4). It was also possible to produce another carbohydrate using the same synthetic pathway. Thus, mono-protection of THF diol 5 followed by oxidation of the remaining free primary hydroxy group to the carboxylic acid and a final hydrogenolysis gave (+)-D-chitaric acid (7) with a yield of

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• ] with bisoxazoline catalyst 33, we have assigned the S,S configuration to the major isomer of product 32. By hydrogenolysis, we could now convert such a sample (40% ee) into 25. The product S,S-25 was formed as the dominant product (35% ee) thus confirming our previous assignment. Under mild basic

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• -oxazolopiperidines 52 with 58% yield and 79:21 dr. Further reduction and hydrogenolysis of 52 in the presence of Pd/C led to aminoester 53 which was converted to (S)-piperidin-2-phosphonic acid (54) through acidic hydrolysis and subsequent treatment with propylene oxide in 42% overall yield and 58% ee (Scheme 13

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• presence of a catalytic amount of Pd on activated charcoal under hydrogenolysis. Thus, we explored the substrate scope using β-N-arylamido benzyl ester or β-N-arylamido p-methoxybenzyl ester as starting materials for the oxidative coupling reaction shown in Figure 2. Towards this end, β-N-aryl amido

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• diastereoselectively converted with a Grignard reagent into the amine 53 as a key step of the synthesis [78]. Cbz protection followed by ozonolysis with subsequent reductive amination and hydrogenolysis led to the 1,3-diamine 54. The cyclisation to the guanidine functionality was achieved with the novel

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• in terms of product purity. Hydrogenolysis of 42 on palladium in ethanol/HCl followed by acetylation of the amino group furnished the target acetylated 3-fluoro-D-GlcNAc 5 as a chromatographically separable mixture of anomers (Table 1). Addition of HCl was found necessary to effect a clean

Diversity-oriented synthesis of analogues of the novel macrocyclic peptide FR-225497 through late stage functionalization

• Jyotiprasad Mukherjee,
• Suman Sil and
• Shital Kumar Chattopadhyay

Beilstein J. Org. Chem. 2015, 11, 2487–2492, doi:10.3762/bjoc.11.270

• solution phase peptide coupling between L-Phe-D-Pro-OMe (6) (prepared by hydrogenolysis of the corresponding carbamate 5) and L-Cbz-Phe-OH (7) followed by elaboration of the resulting tripeptide 8 via N-terminus deprotection leading to 9 followed by a second peptide coupling of the latter with the known

Total synthesis of panicein A₂

• Lili Yeung,
• Lisa I. Pilkington,
• Melissa M. Cadelis,
• Brent R. Copp and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 1991–1996, doi:10.3762/bjoc.11.215

• decided to selectively reduce the ketone to an alcohol – this would allow for the uncomplicated hydrogenolysis of the olefin. Following this, subsequent oxidation of the alcohol would give the desired ketone 13. The reduction of ketone 12 to alcohol 14 with NaBH4 was complete after a reaction time of 10

• minutes, giving 14 in an excellent 94% yield. Hydrogenolysis of the alkene in 14 using Pd/C in MeOH proceeded in 2 hours, providing alcohol 15 which was then oxidised to the desired ketone 13 with Dess–Martin periodinane in 75% yield over two steps. Although this approach was ultimately two steps longer

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

• -trichloroethyl)malonate to give the mixed malonyl derivatives 8a and 9a, respectively, were followed either by a palladium-catalyzed hydrogenolysis of the benzyl moiety to give 8b [26], or by a selective chemical removal of 2,2,2-trichloroethanol with Zn/AcOH to give 9b [27]. c) Enzymatic synthesis of symmetric

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

• 328 in ethanol saturated with ammonia was heated in a stainless sealed tube for 3 days to deliver the pyridinone derivative 329 (87%). Further, chlorination of the pyridinone 329 afforded the chloropyridine 330 (93%). Subsequently, hydrogenolysis of the pyridine derivative 330 gave the target

Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

• Qinggang Mei,
• Chun Wang,
• Zhigang Zhao,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 1220–1225, doi:10.3762/bjoc.11.135

• with reduced double bond. Then we tried a transfer hydrogenolysis method using ammonium formate/10% Pd/C [27], but the result was not improved. The desired product icaritin (3) was finally obtained in 84% yield from 10 when we used 1,4-cyclohexadiene/10% Pd/C in MeOH [28]. Hence, we optimized a

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

• -opened unstable diformyl intermediate (I1), which after work-up was immediately used without further purification (for several similar types of acyclic diformyl intermediates, see references [40][41][43][44]). Thus, the crude material was submitted to catalytic hydrogenolysis and after N-deprotection

• hydrogenolysis, followed by reductive cyclization, to give the corresponding indolizidine ester (±)-9 in 40% yield. Finally, ester reduction with LiAlH4 in THF resulted in epitashiromine (±)-10 [32][34][39] in 53% yield after isolation by chromatography (Scheme 3). The stereochemistry of (±)-epitashiromine was