Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• )-mediated cyclization. Neither of the reported spectral data for dihydrorosefuran match those of the synthetic product, suggesting that the isolated compound from Tagetes mendocina is in fact the natural product rosiridol, while the real structure of the product from Artemisia pallens remains unknown

• same structure was attributed to an isolated substance from the Argentinean herb Tagetes mendocina [9], although not all of its spectroscopic features did match point by point with those previously reported. This made us think that this could be a case of misassigned natural product [10], hence we

• those published for the allegedly dihydrorosefuran isolated from Artemisia pallens nor with those reported for the compound from Tagetes mendocina (see Table 1 and Table 2). The 13C NMR data of compound 1 are quite similar to those of the natural product isolated from T. mendocina, except for the

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• natural product preussochromone D (30) reported by Koert et al. [13]. The synthesis commenced with the efficient production of alcohol 26 from 5-hydroxy-4H-chromen-4-one (25, Scheme 5) [14]. The ketoester moiety was build up via oxidation and nucleophilic addition of methyl diazoacetate, yielding alcohol

• diastereomer not shown) via transition state VII where pseudo-1,3-strain is minimized. Nineteen further steps were necessary to give the naturally occurring jatrophen 51. (−)-Hopeanol In the synthesis of the polyphenolic natural product (−)-hopeanol (59), Nicolaou et al. used an α-ketoester moiety as a

• pentacyclic, antiproliferative quinoline alkaloid camptothecin (65), Peters et al. used an α-ketoester moiety in an auxiliary controlled approach towards the only stereogenic center present in the natural product (Scheme 10) [25]. First, the ketoacid 60 was esterified with 8-phenylmenthol (61) to yield the α

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• 33% (90% ee) over eight linear steps, establishing S configuration for the natural product from S. spectabilis that is likely reflected in the corresponding portion of hangtaimycin. A key step in the synthesis is the elimination of a MOM group using KH and 18-crown-6 that must be carried out with

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• structure is an important scaffold which can be found in many pharmaceutical active natural products and synthetic medicinal compounds [2]. Pramanicin, for example, is a 2-pyrrolidone-containing natural product isolated from a lactose-containg liquid fermentation of a sterile fungus growing in grass which

Enzymes in biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1131–1132, doi:10.3762/bjoc.18.116

• -Institut for their professional support. I wish the readers of this issue some stimulating new insights into enzyme research in natural product biosynthesis. Jeroen S. Dickschat Bonn, August 2022

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• , which extends the insights into P450-mediated biaryl coupling reactions in biosynthesis. Keywords: biaryl coupling; cytochrome P450; dimerization; isoflavone; natural product; Introduction Dimerization is a ubiquitous biotransformation in nature. Almost all forms of life, including bacteria, fungi

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• , antifungal, nematicidal, and cytotoxic activities (Figure 1) [1][2][3]. Since the discovery of the natural azoxy compound macrozamin in 1951 as the first example of a nitrogen–nitrogen bond-containing natural product [4], azoxy compounds have been isolated from various natural sources including bacteria

• distinct mechanism is employed in the biosynthesis of valanimycin, an aliphatic azoxy natural product. This involves the N-hydroxylation of isobutylamine, mediated by the flavin-dependent monooxygenase VlmH [15][16][17], and the following formation of O-(ʟ-seryl)-isobutylhydroxylamine by the tRNA-utilizing

• N2H4-detecting reactivity-based screening led to the identification of four new analogs and two types of biosynthetic gene clusters of azodyrecins, demonstrating its utility in natural product discovery and deorphanization of biosynthetic gene clusters. Evaluation of cytotoxicities of azodyrecins A

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• and biosynthetically constructed by two sequential DTSs from the common C20 linear allylic diphosphate GGDP [29]. Terpentetriene was the proposed biosynthetic intermediate of terpentecin, an anticancer and antibiotic natural product isolated from Kitasatospora griseolosporeus MF730-N6 in 1985 [24][30

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• Jamshid Amiri Moghaddam Huijuan Guo Karsten Willing Thomas Wichard Christine Beemelmanns Chemical Biology Leibniz Institute for Natural Product Research and Infection Biology e.V., Hans-Knöll-Institute, Beutenbergstraße 11a, 07745 Jena, Germany Bio Pilot Plant, Leibniz Institute for Natural

• Product Research and Infection Biology e.V., Hans-Knöll-Institute, Beutenbergstraße 11a, 07745 Jena, Germany Institute for Inorganic and Analytical Chemistry, Friedrich Schiller University Jena, Lessingstr 8, 07743 Jena, Germany Biochemistry of Microbial Metabolism, Institute of Biochemistry, Leipzig

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• Abstract Four new phenolic siderophores were isolated from the actinomycete Nocardia altamirensis along with the known natural product amamistatin B and a putative biosynthetic shunt product. The structures of all compounds were elucidated through 1D and 2D NMR analyses as well as mass spectrometry. The

• under the assumption of a shared biosynthetic origin. Compound 6 shows an optical rotation of = −10.6, which is consistent with the published value of pseudomonin A ( = −9.5) [12]. This natural product is structurally closely related to 6, featuring a terminal amide instead of a carboxylic acid

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• synthesis of sesquiterpene natural product derivatives [38][39] and the carbonyl olefin metathesis leading to 2,5-dihydropyrroles [40]. Herein we present our investigation on the ability of the hexameric capsule 16 to act as a supramolecular self-assembled organocatalyst for a series of unimolecular

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• construct a 3,4-fused tricyclic indole in a late stage of their total synthesis. Specifically, Michael-type addition of compound 4 took place regio- and diastereoselectively at the indole C3 position, furnishing tricyclic compound 5 (77%) which was then elaborated into the target natural product 6 in two

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• structurally related compounds for SAR studies. Of course, this approach is not limited to the development of HDAC inhibitors, but should be suitable for all kinds of natural product modifications. However, the structural motif of the natural products shown in Figure 2 is suitable to illustrate the concept. In

Earth-abundant 3d transition metals on the rise in catalysis

• Nikolaos Kaplaneris and
• Lutz Ackermann

Beilstein J. Org. Chem. 2022, 18, 86–88, doi:10.3762/bjoc.18.8

• , Germany 10.3762/bjoc.18.8 Keywords: C–H activation; 3d transition metals; green chemistry; late-stage functionalization; sustainability; Transition metal catalysis has emerged as a transformative platform for the assembly of increasingly complex compounds, with enabling applications to natural product

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• natural product synthesis, pigments and dyes. Different variety of α-amino carbonyls [2], α-amino acids [3] and 1,2-diamines were prepared from the nitriles using homogeneous and heterogeneous catalysis [4][5][6]. One of the astonishing aspects of nitriles is that it can be easily converted to amines

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• reactivated by protonation for further cyclisation steps, while previously discussed intra- and intermolecular hydrogen transfers are not supported. Furthermore, the isolation of the new natural product (2S,3S,7S,10R)-guaia-1,11-dien-10-ol from patchouli oil is reported. Keywords: biosynthesis; DFT

• natural product 17 [HRMS–ESI (m/z): 221.1904 [M + H]+, calculated for C15H25O+ 221.1900 and [α]D25 = −7.7, (c 0.26, benzene)] whose structure was elucidated by NMR spectroscopy (Table 1 and Figures S29–S35 in Supporting Information File 1). The 13C NMR spectrum showed signals for 15 carbons, including

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• 0.5% TFA in DCM. The Trt group was removed with aqueous solution of TFA to give 9-mer peptide 10 in good yield. The carboxylic acid of 9-mer peptide 10 was converted to the methyl ester with MeI and K2CO3 in DMF [18], delivering the final natural product hoshinoamide A in 2% yield (10 mg). The

• spectroscopic data of synthetic hoshinoamide A were in excellent agreement with the data previously reported for the natural product. Conclusion In summary, we have completed the first total synthesis of hoshinoamide A. By combining the liquid and solid-phase peptide synthetic strategy, hoshinoamide A was

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• on PIFA-initiated oxidative 5-exo-trig cyclization of 2-(3-butenyl)quinazolin-4(3Н)-ones, in turn prepared by thermal cyclocondensation of the corresponding 2-(pent-4-enamido)benzamides. The products obtained have a good natural product likeness (NPL) score and therefore can be useful for the design

• of natural product-like compound libraries. Keywords: [bis(trifluoroacetoxy)iodo]benzene PIFA; nitrogen heterocycles; oxidative cyclization; pyrrolo[1,2-a]quinazolines; Introduction An important design concept in current drug discovery includes structural modifications of naturally occurring

• their suitability for the synthesis of compound libraries relevant to medicinal chemistry. While many chemoinformatic tools are available for that purpose, we have turned our attention to Ertl’s natural product likeness (NPL) score since the target compounds were designed as natural product analogs [1

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• first prepared synthetically before its isolation from natural crude material, employing a stereoselective addition of an aryl Grignard reagent to a five-membered chiral cyclic nitrone derived from ᴅ-arabinose [2]. Its analytical data were consistent with those for the later isolated natural product

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• groups for phenols) and was further utilized in the first total synthesis of the natural product nobilone. Keywords: cross-dehydrogenative coupling; cyclization; fluorenones; nobilone; total synthesis; Introduction Fluorenones are an important class of aromatic natural products, and since the

• -radical reagents [62]. An extremely poor yield was further obtained with methylenedioxy substrate 15p. Our application of this new protocol to the first total synthesis of the natural product nobilone (1d) is depicted in Scheme 7. The commercially available phenol 16 was TBS-protected to give compound 17

• , TBHP-mediated radical cyclization is applicable to a wide variety of primary and secondary benzylamines bearing electron-donating and electron-withdrawing groups to synthesize fluorenones in poor to good yields, and utilized this method for the first total synthesis of the fluorenone natural product

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• from the above work from the Gademann group, Kalmode et al. incorporated the same synthetic strategy into their total synthesis of racemic periconianone A [12]. Interestingly, these authors not only tested the natural product for neural anti-inflammatory activity but also the two immediate synthetic

• reduction in conjugation. Another example of a tandem α-ketol rearrangement was used in the total synthesis of delitschiapyrone A (49), a cytotoxic natural product with previously demonstrated efficacy against several cancer cell lines. The final steps of the synthesis include a Diels–Alder reaction between

• continued development in these areas can be expected in the coming years. It is becoming apparent that nature also utilizes these rearrangements in natural product biosynthesis, and one might expect to see an increase in the discovery of enzymes governing these reactions. Generalized α-ketol or α-iminol

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• -spectrum biological functions which include antifungal [9][10][11] and antibacterial activities [12][13][14]. Natural product scaffolds isolated from species of this genus have contributed immensely as leads to drug discovery and development [15]. For instance, clofazimine [16], the antimycobacterial agent

• used for the treatment of leprosy and inflammation was inspired by the natural product phenazine [17][18]. Also, pseudomononic acid (mupirocin) isolated from Pseudomonas fluorescens by Fuller and co-workers in 1971 was discovered to possess novel antibacterial activities against 310 clinical isolates

• methanolic extract from a small-scale culture of Pseudomonas sp. UIAU-6B in modified SGG medium indicated the presence of some interesting peaks with molecular ions which gave no hits when they were searched in natural product databases (Antibase). At the same time, the 1H NMR fingerprints suggested the

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• . The Hg(OTf)2-catalyzed isomerization of the double bond in compound 205 yielded thermodynamically favorable isomer 206 as a major product [123]. In 2010, Ravindar et al. developed the total synthesis of the steroidal natural product hippuristanol (211) starting from 11-ketotigogenin 208 (Scheme 63

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• the synthesis of the simple phenanthridine natural product trisphaeridine (3). Results and Discussion To investigate the scope and limitations of the reaction we initially opted to prepare a number of biaryl substrates possessing one aromatic electron accepting ring possessing a variety of methoxy

• was demonstrated to be useful for the synthesis of the natural product trisphaeridine (3) [17]. Exposure of 1-bromo-2,4,5-trimethoxybenzene (19) to Suzuki–Miyaura coupling reaction conditions with boronic acid 20 resulted in the formation of aldehyde 21 (Scheme 5). Treatment of 21 with hydroxylamine

• proceeding by means of the initial generation of an iminyl radical that cyclizes onto the electron-rich aromatic ring or through the formation of a radical cation on the electron-rich benzene ring. Finally, the methodology has successfully been applied to synthesizing the natural product trisphaeridine

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• synthesizing betulinan A, a natural product isolated from Lenzites betulina [2], in two steps starting from commercially available starting materials. Analogs of the natural product 5a, such as 5b can also readily be prepared from the corresponding diarylquinone 3a (Scheme 2). Conclusion In summary, we have

• product. The reactive aryldiazonium salt is synthesized in situ, minimizing risks and enabling scale-up. The chlorine substituents on the quinone were successfully functionalized as part of the synthesis of natural product betulinan A, proving that this work may further facilitate the synthesis of new