Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• et al. applied a fluorescence-based DNA cleavage assay coupled with HiTES to Streptomyces clavuligerus and identified the steroid 11α-hydroxyprogesterone (14) as an effective elicitor and characterized 10 cryptic enediyne-derived natural products, designated clavulynes A (15) and B–J with unusual

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• acetylenic scaffolds comprised of enediyne units are known to behave as good electron acceptors [15][16], and we became interested in combining the IF-DTF scaffold with such motifs to generate novel multi-redox systems. For example, the radiaannulene moiety RA shown in Figure 1 (or its truncated counterpart

• with one of the exocyclic enediyne units removed) [17][18] is a particularly good electron acceptor as it gains 14π-aromaticity upon reduction. In this work, we also want to further explore pyrrolo-annelated IF-DTFs with different substituents on the nitrogen atom, and the functionalization at the

• easily degrade, which made their characterization somewhat difficult (vide infra). We also targeted other enediyne acetylenic scaffolds with IF as central core as shown in Scheme 5. Starting from IF dione 1, compounds 24 and 25 were synthesized via Ramirez/Corey–Fuchs dibromo-olefinations. Four-fold

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• Streptomyces, are especially noted, accounting for more than 800 metabolites of actinomycetes origin [11], which include the antiinfective aminoglycoside gentamicin [13], antidiabetic glycoside acarbose [14], glycopeptide antibiotic teicoplanin [15], enediyne antitumor component of drug-antibody conjugate

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• -2,7-diyne reacted chemo- and stereoselectively in a Diels–Alder reaction with N-phenylmaleimide affording the tricyclic products as a mixture of two separable diastereoisomers, the configuration of which was estimated by DFT computations. The reported enediyne metathesis paves the way to the

• enantioselective enyne metathesis yielding chiral building blocks for compounds with potential biological activity, e.g., norsalvinorin or cacospongionolide B. Keywords: Diels–Alder reaction; enediyne; enyne metathesis; ring-closing metathesis; ruthenium precatalyst; Introduction Among the plethora of metathetic

• significantly more demanding strategy uses prochiral substrates and chiral metathesis precatalysts. Despite many examples of enantioselective RCM, only two examples of an enantioselective RCEYM have been reported (both featuring a dienyne substrate and a Schrock complex) [21][30], no enantioselective enediyne

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• habitat [6][7]. Their secondary metabolite machinery is activated in the sea, as indicated by the isolation of enediyne antitumor antibiotics from marine invertebrates. Namenamicin [8] and the shishijimicins [9], the chalicheamicin-type enediyne polyketides, were isolated from a colonial tunicate. These

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• )-one [29] derivatives, various enediyne [30][31][32], proflavine [33], N-nitroso carboxamide [34], naphazoline [35] and triazole [36] derivatives, azido carbonyl compounds [37] and N,O-diacyl-4-benzoyl-N-phenylhydroxylamines [38]. O-Acyl amidoximes, ketoximes and aldoximes (I, II and III, respectively

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

• stereoselective Michael addition of aldehyde 4 to methyl vinyl ketone [7][8][10] followed by chemoselective elaboration of the two carbonyl functions. Finally, aldehyde 4 was traced back to the commercially available starting material (S)-citronellal (5). On the other hand, a more rarely used enediyne metathesis

• ), which compares favorably with the previous synthesis of 1 from (+)-dihydrocarvone (10 steps, 6.9% overall yield) [6]. Scheme 3 depicts our first attempts to realize an alternative domino metathesis strategy using enediyne 7. Ozonolysis of the unsaturated acetal 10 gave aldehyde 23 [17][18] that was

• 28 with ylide 13 and alkyne formation with butyllithium in a one-pot procedure then gave rise to enediyne 7 in excellent yield. Unfortunately, all attempts to achieve a domino metathesis of 7 to hydroazulene 6 only met with failure. Thus, neither the Grubbs catalysts 22 or 29, nor the Hoveyda

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• NRPS or mixed NRPS/PKS clusters. This situation is hence quite similar to myxobacteria [56]. An unexpected finding, however, was the discovery of an enediyne PKS gene in H. aurantiacus 114-95T. Enediynes are highly potent antibiotics, causing DNA-strand scissions. Although an impressive number of 87

• enediyne clusters could be identified in sequencing projects over the past years, comparatively few loci were retrieved from microbes outside the actinobacteria [124]. This suggests an event of horizontal gene transfer (HGT) in H. aurantiacus 114-95T. Analysis of a large NRPS/PKS cluster in the same strain

Natural products in synthesis and biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 1897–1898, doi:10.3762/bjoc.9.223

• fascinating as is spectacularly demonstrated by the prominent examples of maitotoxin [3], the largest non-polymer secondary metabolite known to date, or calicheamycin (Figure 1), which possibly holds the record in carrying the most diverse functional groups including an enediyne subunit, a deoxysugar, an

Highly stereocontrolled synthesis of trans-enediynes via carbocupration of fluoroalkylated diynes

• Tsutomu Konno,
• Misato Kishi and
• Takashi Ishihara

Beilstein J. Org. Chem. 2012, 8, 2207–2213, doi:10.3762/bjoc.8.249

• ; carbometallation; diyne; enediyne; fluorine; highly regioselective; highly stereoselective; Introduction trans-Enediynes (trans-hex-3-ene-1,5-diynes), as shown in Figure 1, are well-recognized as one of the most important building blocks because they are frequently utilized for the synthesis of π-conjugated

• -coupling reaction of readily accessible 2,3,3,3-tetrafluoro-1-iodo-1-propene (1) and the following HF elimination reaction. The thus-obtained CF3-enediyne could participate in the carbocupration with various higher-ordered cyanocuprates very well to give the corresponding vinyliodides in good yields

• . Finally, the thus-obtained iodide underwent a smooth Sonogashira cross-coupling reaction to afford the various desired trans-enediyne derivatives in high yields. trans-Enediyne. Regio- and stereoisomers. Synthetic strategy for the preparation of trifluoromethylated diynes. Preparation of various enynes. A

Highly enantioselective access to cannabinoid-type tricyles by organocatalytic Diels–Alder reactions

• Stefan Bräse,
• Nicole Volz,
• Franziska Gläser and
• Martin Nieger

Beilstein J. Org. Chem. 2012, 8, 1385–1392, doi:10.3762/bjoc.8.160

• published total synthesis of Taxol (2) by Nicolaou. Two different [4 + 2]-cycloaddition reactions were applied to set up each of the two six-membered rings of the target molecule [9][10]. As a final example, Dynemicin A (3) should be mentioned, which is an enediyne consisting of a complex heterocyclic

Sonogashira–Hagihara reactions of halogenated glycals

• Dennis C. Koester and
• Daniel B. Werz

Beilstein J. Org. Chem. 2012, 8, 675–682, doi:10.3762/bjoc.8.75

• in a twofold Sonogashira reaction with an excess of phenylacetylene resulted in a chemoselective monoalkynylation of the pseudoanomeric position in quantitative yield (Scheme 2). Even the use of an elevated temperature did not lead to the formation of an enediyne. Further refunctionalization of the

Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates

• Wang-Yong Yang,
• Samantha A. Marrone,
• Nalisha Minors,
• Diego A. R. Zorio and
• Igor V. Alabugin

Beilstein J. Org. Chem. 2011, 7, 813–823, doi:10.3762/bjoc.7.93

• remarkable properties, the mechanism of DNA cleavage by photoactivated alkynes and enediynes is still not fully understood. Some light has been shed on the mechanism by the sequence selectivity of DNA cleavage in internally labeled DNA oligomers [28]. All enediyne-, alkyne-, and fulvene-based lysine

• mechanisms, such as guanine alkylation [29][30][31][32][33][34][35], which combine with the oxidative DNA damage to account for the efficient ds cleavage of plasmid DNA. In the case of enediyne conjugate 2, the additional DNA-cleavage mechanism may be provided by either photo-Bergman cyclization [3][36][37

• ][38][39][40][41][42][43][44] (akin to such well-known DNA cleavers as enediyne antibiotics) [45][46] or C1–C5 cyclization [47][48][49][50][51][52] (Figure 2). In the latter process, which transforms enediynes into indenes, four hydrogens are transferred from the environment (two as H-atoms and two as

Synthesis of 5-(2-methoxy-1-naphthyl)- and 5-[2-(methoxymethyl)-1-naphthyl]-11H-benzo[b]fluorene as 2,2'-disubstituted 1,1'-binaphthyls via benzannulated enyne–allenes

• Yu-Hsuan Wang,
• Joshua F. Bailey,
• Jeffrey L. Petersen and
• Kung K. Wang

Beilstein J. Org. Chem. 2011, 7, 496–502, doi:10.3762/bjoc.7.58

• enediynes. Specifically, treatment of the benzannulated enediyne 1a with potassium tert-butoxide in refluxing toluene for six hours promoted a 1,3-prototropic rearrangement to produce, in situ, the benzannulated enyne–allene 2a, which in turn underwent a sequence of Schmittel cascade cyclization reactions

• sensitive to the steric requirement of the substituent at the alkynyl terminus. The benzannulated enediyne 1b with a sterically demanding 2,6-dibromophenyl substituent was also smoothly converted to 3b [6]. With 1c having a 1,1'-binaphthyl substituent, a 1:1 mixture of the syn and the anti atropisomers of

• -(methoxymethyl)-1-naphthyl group at one of the alkynyl termini of the benzannulated enediyne system, the resulting naphthyl-substituted benzo[b]fluorenes could be regarded as 2,2'-disubstituted 1,1'-binaphthyls with two additional substituents at the 3 and 4 positions. The versatility of 1,1'-binaphthyl-2,2

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• . Oxidative release of 160 followed by Swern oxidation and Takai reaction provided the terminal vinyl iodide 161. Final Pd0-catalyzed coupling of alkyne 157 with vinyl iodide 161 gave the enediyne 162, which underwent selective hydrogenation and desilylation to give (+)-parviflorin (153). In 1997, Trost’s