Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• thorough biological investigations (as have been suggested by the European Food Safety Authority, EFSA [19]), we considered it useful to supply a more straightforward synthesis of this compound, for which we here propose the obvious name decarboxyaltenusin. Results and Discussion In a retrosynthetic

• analysis, we envisioned a Suzuki coupling of two suitably substituted arenes. Silyl protecting groups like the tert-butyldimethylsilyl group (TBS) were considered appropriate for all projected reaction steps. The boronate moiety 6a was prepared starting with 4-methylcatechol (2), which was initially

Synthesis of 6,13-difluoropentacene

• Matthias W. Tripp and
• Ulrich Koert

Beilstein J. Org. Chem. 2020, 16, 2136–2140, doi:10.3762/bjoc.16.181

• two fluorine substituents was investigated. The retrosynthetic analysis for this strategy is shown in Scheme 1. The formation of the C5,5a-bond colored in red could be accomplished by an intramolecular Friedel–Crafts type acylation with the acylium-cation intermediate 6. The corresponding carboxylic

• -difluoroanthracene. This strategy could be applicable for the synthesis of differently substituted 6,13-difluoropentacenes as well. Structures of pentacene and fluorinated pentacenes. UV–vis spectrum of F2PEN 5 in CH2Cl2. Retrosynthetic analysis of F2PEN 5. Synthesis of F2PEN 5. Decomposition of diol 13 in solution

Synthesis of the tetrasaccharide repeating unit of the O-specific polysaccharide of Azospirillum doebereinerae type strain GSF71^T using linear and one-pot iterative glycosylations

• Arin Gucchait,
• Pradip Shit and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 1700–1705, doi:10.3762/bjoc.16.141

• glycosylation in one pot was developed and is reported herein. Results and Discussion At the beginning, the retrosynthetic analysis suggested that a sequential glycosylation reaction using judiciously protected monosaccharide thioglycosides could be the best strategy for achieving the desired tetrasaccharide 1

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• . Mechanistic pathways for the reaction between cyclic anhydrides and imines. Retrosynthetic analysis of the target compounds. Reaction of 6,7-dimethoxy-3,4-dihydroisoquinoline (18) with anhydrides 5–8. Reagents and conditions: xylene, inert atmosphere, 120 °C, 6 h. Reaction of 1-methyl-3,4-dihydroisoquinoline

• system using the Castagnoli–Cushman reaction between 6,7-dimethoxy-3,4-dihydroisoquinoline (18) and its 1-substituted derivatives 19 and 20, and the anhydrides 5–8. This approach also could allow the construction of bioisosteric O- and S-analogs of the target systems as it is shown by the retrosynthetic

• analysis (Scheme 3). For the present studies the employed starting imines 18–20, were prepared by a Bischler–Napieralski condensation, using procedures available in the literature [30][31]. Reactions of 6,7-dimethoxy-3,4-dihydroisoquinoline (18) with anhydrides 5–8 The reaction between 18 and anhydrides 5

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

• Jan Geldsetzer and
• Markus Kalesse

Beilstein J. Org. Chem. 2020, 16, 670–673, doi:10.3762/bjoc.16.64

• ][19][20], whereas the (Z)-bromide 4 can be generated in a four-step sequence with a 39% overall yield, including a palladium-catalyzed, stereoselective dehalogenation [21][22][23][24][25]. Retrosynthetic analysis of chondrochlorene A (1). Synthesis of amide 3 [16][17][18][19][20]. TIPDSCl2 = 1,3

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• reducing end of the target pentasaccharide that will allow further conjugation using the terminal amine without affecting the glycosidic stereochemistry. Further retrosynthetic analysis of the target pentasaccharide 1 revealed that a [3 + 2] strategy will be the most suitable one for the total synthesis of

• repeating unit in the form of its 2-aminoethyl glycoside. Retrosynthetic analysis for the synthesis of the target pentasaccharide 1. Synthesis of the disaccharide acceptor 5. Synthesis of the trisaccharide acceptor 11. Synthesis of the non-reducing end disaccharides (16a and 16b). Synthesis of the target

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• using a HoloMonitor® M4 time-lapse cytometer. Cell proliferation was followed for 14.5 h (30 min between images) and corresponding time-lapse movies are available in Supporting Information Files 2–5, scale bar 50 µm. Comparison of optical properties of different silicon rhodamines. Retrosynthetic

• analysis of the proposed small molecule bimodal probe [18F]16 for both optical and PET imaging of cancer cells with up-regulated mitochondrial activity. Optimization of the HD rearrangement of 19 and subsequent reaction with xanthone 17 to the silicon rhodamine dye 15. Comparison of optical properties of

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• ]. Nevertheless, to the best of our knowledge, no asymmetric entry to this class of natural products has been described. Our retrosynthetic analysis of 5 is depicted in Scheme 1. The prenyl side chain would be introduced by transition metal-catalyzed cross coupling of vinyl iodide 9. Compound 9 in turn could be

• transformation requires enzymatic catalysis in nature. Selected members of the acremine family [3][4][5]. Retrosynthetic analysis of acremine F (5). Total synthesis of acremine F (5). Synthesis of acremines A and B through selective oxidation of acremine F. Proposed biomimetic dimerization of 5. Attempted

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• reasonable positioning for a reaction with Cys263. B) Ligand interaction diagrams for atrop-O-benzyl-desmethyl-abyssomicin C (left) and compound 2 (right), showing similar interactions and similar shape. Retrosynthetic analysis of the truncated derivatives 1 and 2 of abyssomicin C. Synthesis of the building

An efficient synthesis of the guaiane sesquiterpene (−)-isoguaiene by domino metathesis

• Yuzhou Wang,
• Ahmed F. Darweesh,
• Patrick Zimdars and
• Peter Metz

Beilstein J. Org. Chem. 2019, 15, 858–862, doi:10.3762/bjoc.15.83

• sesquiterpene (−)-isoguaiene (1) using either a trienyne or a dienediyne metathesis and highly diastereoselective organocatalytic Michael additions of aldehydes derived from 5 as the key steps. Structures of the sesquiterpene (−)-isoguaiene (1) and the trisnorsesquiterpene clavukerin A (2). Retrosynthetic

• analysis for (−)-isoguaiene (1). Synthesis of 1 by relay metathesis of trienyne 3. a) HC(OMe)3, 4 mol % LiBF4, MeOH, reflux, 80%; b) (i) BH3·Me2S, THF, 0 °C to rt, (ii) 30% H2O2, 10% NaOH, 0 °C to rt, 97%; c) 5 mol % TPAP, NMO, CH2Cl2, rt, 97%; d) 13, THF, rt to reflux, 96%; e) 25 mol % TsOH, THF, H2O

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• incorporation of an amidine moiety allows for regioselective alkylations with 14 and facilitates the synthesis of novel N7-substituted adefovir analogues. Adefovir (1) and its prodrug 2. Retrosynthetic analysis of 6 to synthons 9 and 10. Retrosynthesis of 6 to synthons 14 and 3. HMBC spectrum confirms N7

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• or a Tyr-Tyr linkage. Results and Discussion Synthesis of the biaryl bicyclic peptide 1 We first planned the synthesis of the biaryl bicyclic peptide 1 incorporating a Phe-Phe linkage based on the retrosynthetic analysis depicted in Scheme 1. According to this analysis, the key steps are the

• macrolactamization step. This work constitutes the first solid-phase synthetic approach to biaryl bicyclic peptides. The method described is general and allows access to a diversity of novel Phe- and Tyr-containing biaryl bicyclic peptides. Structure of biaryl bicyclic peptides 1–3. Retrosynthetic analysis for the

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• the influence of the acceptor structure and reactivity on the stereoselectivity of glycosylation reactions [49] and give information on the design of building blocks for the synthesis of long CS sequences. Retrosynthetic analysis for the preparation of CS oligosaccharides. Lev = levulinyl; Piv

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• of linkers are unsuitable, as they rendered the peptide inactive (results not shown). However, disulfide-bonded linkers retained activity, presumably by cleavage in the reductive milieu of cancer cells, if connected via a short ester or amide linkage at the C-terminus. The retrosynthetic analysis

• ). Retrosynthetic analysis of the modular attachment linker tubugi-1-SSPy (3). Synthesis of tubugi-1-SSPy (3): a) LiOH·H2O, THF/H2O, 0 °C → rt; b) Ac2O, py; c) 4, HBTU, DMF, DIPEA, MeOH, under N2 atmosphere, 42% (3 steps). Synthesis of the tubugi-1–NPY conjugate [K4(C(tubugi-1)-βA-),F7,L17,P34]-hNPY (8). Toxin

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• functionalized side chains are introduced prior to coupling and ring closure to afford 8. This new synthetic route would be more convergent and efficient for the preparation of 3. Retrosynthetic analysis led to 9 and 10 as two key synthons, which would be assembled via a Mitsunobu–Fukuyama reaction, and

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

• strongylodiol I The retrosynthetic analysis for strongylodiols H and I is delineated in Scheme 1. We envisaged that the target molecules strongylodiol H (9) and strongylodiol I (10) can be synthesized by a Wittig reaction of a common intermediate aldehyde 14 with triphenylphosphonium Wittig salts 15 and 16

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

• 5 could not only act as a surrogate for C-9 carbonyl but also facilitate installation of an angular methyl group. The retrosynthetic analysis for hyperireflexolide A is depicted in Scheme 1. We envisioned that hyperireflexolide A (1) could be synthesized by metal-catalyzed opening of the epoxide 2

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

• sequential glycosylation strategies. Results and Discussion Keeping in mind our objective to synthesize the SPn 6A tetrasaccharide following stepwise as well as one-pot synthetic strategies based on common building blocks, a retrosynthetic analysis was made which led us to galactose-based donor 2 [26

• linkages could be prepared with a yield and a selectivity which were high enough to allow the one-pot synthesis. The tetrasaccharides associated with the pneumonicoccal serogroup 6. Retrosynthetic analysis. Preparation of D-glucosyl donor 6. Reaction conditions: a) NapBr/PMBCl, NaH, DMF, rt, 12 h, 90% (6a

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• examples. X-ray crystal structure of hydantoin-fused triazolobenzodiazepine 10a. (Displacement ellipsoids are drawn at the 30% probability level.) Retrosynthetic analysis towards 2,5-diketopiperazine fused triazolobenzodiazepine. Ugi 4-CR reaction. Synthesis of diketopiperazine-fused triazolobenzodiazepine

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• efficient stereocontrol. To the best of our knowledge such approach involving a double auxiliary and catalyst stereocontrol was never applied before to asymmetric synthesis of enantioenriched isoindolinones. Results and Discussion Retrosynthetic analysis From a retrosynthetic point of view, (3S)-NH free 3

• active chiral 3-substituted isoindolinones. Esters 12a–e, 13 prepared, isolated yield. Benzamides 6a–d, 7a–e, 8 prepared, isolated yield. Phase transfer catalysts (PTC) used in this study. ORTEP plot of isoindolinone (2R,3S)-3a (CCDC 1590565) [68]. Retrosynthetic analysis of NH free chiral 3-substituted

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• ]. With these issues in mind, we carried out a retrosynthetic analysis (Scheme 2) in which 10, an iodo analogue to the starting material 3, could be generated in a single step via a decarboxylative ring-opening of α-acetyl butyrolactone 8. The iodo analogue 10 could then be used without isolation to

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• retrosynthetic analysis is depicted in Scheme 1. The initial step comprises the photodecarboxylative addition of phenylacetate to commercially available N-(bromoalkyl)phthalimides, yielding the corresponding benzylated hydroxyphthalimidine derivatives as key intermediates. Subsequent acid-catalyzed dehydration

• ]. Molecular structures of AL-12, AL-12B and AL-5. Crystal structures of photoaddition products 3a (left) and 3b (right). Crystal structure of (E)-7a. Side view and front view. Crystal structure of (Z)-8a. Side view and front view. Retrosynthetic analysis of AL-12, AL-12B and AL-5 (in their neutral forms) and

A semisynthesis of 3'-O-ethyl-5,6-dihydrospinosyn J based on the spinosyn A aglycone

• Kai Zhang,
• Shenglan Liu,
• Anjun Liu,
• Hongxin Chai,
• Jiarong Li and
• Lamusi A

Beilstein J. Org. Chem. 2017, 13, 2603–2609, doi:10.3762/bjoc.13.257

• to synthesize other rhamnose analogues. The structures of spinosad and spinetoram. Chemical modifications of spinosyn J and spinosyn L. Retrosynthetic analysis of 3'-O-ethyl-5,6-dihydrospinosyn J. Hydrolysis of spinosyn A and formation of the aglycone and D-forosamine. Synthesis of 3-O-ethyl-2,4-di-O

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• only to symmetrical products and can be detrimental for more fragile molecules such as substituted enantiomerically pure compounds. As shown by a retrosynthetic analysis (Scheme 1), a classical milder approach would consist in preparing first the dipeptide, followed by an intramolecular ester

Synthesis of substituted Z-styrenes by Hiyama-type coupling of oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane

• James R. Vyvyan,
• Courtney A. Engles,
• Scott L. Bray,
• Erik D. Wold,
• Christopher L. Porter and
• Mikhail O. Konev

Beilstein J. Org. Chem. 2017, 13, 2122–2127, doi:10.3762/bjoc.13.209

• established in applying the Buchwald–Hartwig coupling to 15, producing the benzoxocane 24, which contains the carbon skeleton of heliannuol A. Retrosynthetic analysis of heliannuol A. Hydrosilylation of alkynols. Hydrogenation of benzoxocane 24. Pd-catalyzed couplings of oxasilacycloalkenes with aryl iodides