Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• corniculatolides or isocorniculatolides. 2.2 Retrosynthetic analysis Due to the aforementioned biological activities and the low availability from natural sources to provide sufficient material for additional investigations, the combretastatin D series and their isomeric macrolides have become an attractive target

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• for biological screening. The era of scalability [2] in total synthesis prompts researchers in this field to make use of more direct retrosynthetic disconnections with the aid of “radical” retrosynthetic analysis, as the advancement in the area now allows to harness one-electron power in a highly

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• . Impressed by the structural features and biological profiles, our group embarked a project on the total synthesis of this natural product. Herein, we report our stereoselective synthesis of its 6-5-5 tricyclic skeleton. Our retrosynthetic analysis is shown in Scheme 1. For the formation of the D ring with

• natural product aberrarone from the key intermediate cyclopentenone 8 is currently underway, and will be reported in due course. Selected representative natural products with 6-5-5 tricyclic skeleton. Retrosynthetic analysis of aberrarone (1). Synthetic study toward aberrarone (1). Supporting Information

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• ]phenanthridine derivatives and further assessments of their bioactivities are currently in progress in our laboratory. Classification of benzo[c]phenanthridine alkaloids. Representative synthetic strategies for macarpine (1). Retrosynthetic analysis of marcarpine precursor 12 for a partial synthesis. Syntheses

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• . Preparation of racemic 3-propylnorleucin 16a. Unsuccessful direct coupling of amino acid methyl esters with the benzothiazine motif and retrosynthetic analysis of alternative linear reaction routes. a) Synthesis of 2H-benzo-1,4-thiazine amino acid conjugates 19a and 19b and b) 3D renderings of 19a and 19b

Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

• Tanmoy Halder and
• Somnath Yadav

Beilstein J. Org. Chem. 2021, 17, 2915–2921, doi:10.3762/bjoc.17.199

• stereoselective glycosylations. The work provides an access to the trisaccharide repeating unit of the O-polysaccharide of Providencia stuartii O49 with the stereospecific α-p-methoxyphenyl glycoside. Structure of the repeating unit of the lipopolysaccharide of Providencia stuartii O49 serotype. Retrosynthetic

• analysis for the synthesis of the target trisaccharide 1. Synthesis of the monosaccharide building blocks 3, 6, and 7. Linear synthesis of trisaccharide derivative 2. Synthesis of ᴅ-galactose donor 12. One-pot synthesis of trisaccharide derivative 2. Synthesis of trisaccharide derivative 1. Supporting

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• design new synthetic methodologies for reproducing these natural products and their analogues as well as to develop new pharmaceuticals from them. Structures of brevipolides A–O (1 – 15). Retrosynthetic analysis of brevipolide H (8) by Kumaraswamy. Attempt to synthesize brevipolide H (8) by Kumaraswamy

• . (R,R)-Noyori cat. = RuCl[N-(tosyl)-1,2-diphenylethylenediamine)(p-cymene)]. Attempt to synthesize brevipolide H (8) by Kumaraswamy (continued). Retrosynthetic analysis of brevipolide H (8) by Hou. Synthesis ent-brevipolide H (ent-8) by Hou. Retrosynthetic analysis of brevipolide H (8) by Mohapatra

• . Attempt to synthesize brevipolide H (8) by Mohapatra. Attempt to synthesize brevipolide H (8) by Mohapatra (continued). (+)-(IPC)2-BCl = (+)-B-chloro-diisopinocampheylborane. Retrosynthetic analysis of brevipolide H (8) by Hou. Synthesis of brevipolide H (8) by Hou. Retrosynthetic analysis of brevipolide

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• parameters are drawn at 50% probability level. Molecular structure of compound 17a, displacement parameters are drawn at 50% probability level. Retrosynthetic analysis of heterocycles A and B. Free-radical cyclization of N-protected and N-unprotected pyrroles 1a and 2. Synthesis of 2H-pyrido[2,1-a]pyrrolo

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• resulting from the low stability of amino sugar hemiacetals. The prepared polyfluorinated thiodonors and hemiacetals are valuable intermediates in oligosaccharide synthesis and their utility in glycosylation is currently being studied in our group. Retrosynthetic analysis of the target fluoro analogs

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• introduction of a tetrahydroquinoline moiety by direct amination to triflate 7. Retrosynthetic analysis of the pyrrolo[2,3-c]quinoline ring construction. Synthesis of N-substituted 4-aminopyrrolo[3,2-c]quinoline 18. Synthesis of the tetrahydroquinoline moiety through cycloamination. Synthesis of trigonoine B

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• approach to 9,11-secosterols is depicted in the retrosynthetic analysis in Scheme 1. There are two key steps in obtaining the skeleton of the secosterol. The first is (di)hydroxylation at C9 (C11), and the second is C9–C11-bond cleavage, which can be carried out by a well-developed chemical oxidation of

• ; HRMS (m/z): [M + H]+ calcd, 317.1747; found, 317.1755. A) Tetracyclic core of steroids and possible sites of bond cleavages for secosteroids. B)The first 9,11-secosteroid isolated in 1972 [7]. Retrosynthetic analysis of 9,11-secosterols. Synthesis of starting materials. Reagents and conditions: i

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