Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• 1995, was previously identified as a polyamine with C2 symmetry and a 1,3-syn-diol moiety on a C10 carbon backbone – one of very few substituted polyamines to be isolated from nature. Its absolute configuration was later established by our first reported total synthesis in 2010. Herein we report the

• first total synthesis of the enantiomer of pavettamine, ent-pavettamine. The symmetrical structure of the molecule allows for the synthesis of a common C5 fragment that can be divergently transformed into two synthons for later convergent coupling to furnish the target carbon framework. Based on the

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• industrialized total synthesis of a nontrivial natural product. The original experimental protocol was recently improved by replacing the inorganic base (KOH, NaOH) with the amidine base diazobicycloundecane (DBU) as well as ethanol with n-propanol [49]. The type-III Guareschi reaction is a three-component

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• enantioselectivities (85–99% ee; entry 1; Table 25) and used in the total synthesis of terpenoids (Scheme 14) [10]. In the same year, these terpenoids were also prepared by the Stoltz group [11]. Arylboronic acids bearing the appropriate functional groups were identified and the addition reactions to 3-methyl-2

• further used in the work published in 2020 by Bisai et al. for the addition of 4-tolylboronic acid to 3-methyl-2-cyclohexenone in the total synthesis of the aromatic sesquiterpene (−)-ar-tenuifolene (Scheme 16) [12]. Later in 2020, Bisai et al. published the application of the L9/Pd(TFA)2 catalytic system

• organoboron reagents to enones [3][26][35]. Enantioselective β-arylation of cyclohexanone [38]. Application of L2/Pd(OAc)2 in the total synthesis of terpenes [8]. Plausible catalytic cycle for the addition of phenylboronic acid to 2-cyclohexenone catalysed by L3/Pd(dba)2 [40]. Microwave-assisted addition of

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• the strategy has further been successfully applied in the total synthesis of bioactive macrocycles and related natural products. In this context, hundreds of valuable contributions have already been made in this area, and the present review is intended to provide the systematic assortment of diverse

• Prins cyclization strategies, covering the literature reports of the last twenty years (from 2000 to 2019), with an aim to give an overview on exciting advancements in this area and designing new strategies for the total synthesis of related natural products. Keywords: asymmetric; natural products

• . Thus far, several methods have been devised for the construction of substituted tetrahydropyran rings. Since the year 2000, a number of conceptually different reactions have been developed for the efficient construction of THP rings and were eventually employed in the total synthesis of natural

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

• , Yokohama University of Pharmacy, 601 Matano, Totsuka-ku, Yokohama 245-0066, Japan 10.3762/bjoc.17.62 Abstract The first total synthesis of the pyrrolo[2,3-c]quinoline alkaloid trigonoine B (1) was accomplished via a six-step sequence involving the construction of an N-substituted 4-aminopyrrolo[2,3-c

• medicinal chemists. The total syntheses of aplidiopsamine A (2) [5][6][7][8][9] and marinoquinolines 3 [10][11][12][13] have been achieved by various synthetic strategies. Nevertheless, the total synthesis of trigonoine B (1) has not yet been reported. We have been interested in the synthesis of

• MeAαC by the electrocyclization of 3-alkenyl-2-carbodiimidoindole derivatives obtained by an aza-Wittig reaction of indol-2-yl-iminophosphoranes and isocyanates [28]. In this work, we report the first total synthesis of trigonoine B (1) involving the construction of a pyrrolo[2,3-c]quinoline framework

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

• total synthesis sequence. Inspired by several enzymatic oxidations [22][23][24][25], we envisioned to carry out oxidation at C9 in an environmentally benign way using an oxidation by a whole-cell biocatalysis method. The first, and so far the only chemoenzymatic synthesis of 9,11-secosterols using

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• with inversed configuration of the double bond. Several synthetic strategies starting from isocyanate [22][23] or oxindole [4][12] precursors work well only with protected nitrogen(s) in the starting compounds whose preparation and protection/deprotection also lengthens the total synthesis and

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• cytotoxic against a variety of cancer cell lines, and both bohemamine and NP25302 inhibit HL-60 cell adhesion to Chinese hamster ovary cells expressing intercellular adhesion molecule ICAM-1 (CD-54). This interest led us to develop a total synthesis of NP25302 [25] and its 5-normethyl analog and, as

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

• -Leopoldshafen, Hermann-von-Helmholtz-Platz 1, Germany 10.3762/bjoc.17.22 Abstract The total synthesis of decarboxyaltenusin (5’-methoxy-6-methyl-[1,1’-biphenyl]-3,3’,4-triol), a toxin produced by various mold fungi, has been achieved in seven steps in a yield of 31% starting from 4-methylcatechol and 1-bromo

• compound due to the reduced accessibility of the precursors and since no experimental details have been published for the transformation. To continue our efforts in the total synthesis of mycotoxins [8][9][10][11][12][13][14][15][16][17][18] and to provide larger amounts of the polyketide 1 sufficient for

• %. Conclusion The total synthesis of decarboxyaltenusin (1) was achieved in seven steps in a yield of 31% starting from 4-methylcatechol (2) and 1-bromo-3,5-dimethoxybenzene (7), where the longest linear sequence has consisted of five steps. Decarboxyaltenusin turned out to be nontoxic towards human HeLa cells

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• application of various efforts towards the synthesis of inthomycins and their analogues systematically. Keywords: antibiotics; inthomycins; oxazololomycin; Stille coupling; total synthesis; Introduction Inthomycins, alternatively known as phthoxazolins, are a class of compounds in which a methylene

• have generated immense interest among the chemists. Over the past two decades, a wide variety of synthetic strategies have been dedicated towards the synthesis of the inthomycin class of antibiotics. An earlier report on the total synthesis of oxazolomycins provides an overview of the author’s

• Whiting [19][20], several racemic and asymmetric total syntheses of inthomycins A–C (1–3) have been carried out in many research groups (Figure 2). However, only four synthetic strategies that lead to the total synthesis of all three members of inthomycins A–C (1–3) are available (Figure 2, route b, d, h

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• these targets highly relevant when considering total synthesis. Since Tursch's pioneering work, several total and formal syntheses of homotropane alkaloids released by coccinellids have been carried out, contributing to a more accurate chemical and biological understanding of these alkaloids

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• of a triple bond, which has ultimately led to the total synthesis of several natural compounds [2][8]. The gold-catalyzed rearrangement of suitably substituted propargylic esters in particular provides a platform for cascade processes that involve a cationic or an allene intermediate generated in the

• to carry out a complete computational analysis to evaluate the entire reaction profile and to help us validate our hypothesis before embarking on a potential total synthesis, involving such a process, in the future. In parallel, a few suitable substrates were also subjected to gold catalysis with the

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• -workers used a platinum-catalyzed intramolecular [3 + 2] cycloaddition of a propargylic ketal derivative to complete the total synthesis of Kopsia indole alkaloids [67] (Scheme 11). The platinum-catalyzed intramolecular [3 + 2] cycloaddition of propargylic ketal derivative 142 afforded indoline 143 in 58

• reaction. Total synthesis of natural products reported by Yang and co-workers applying rhodium-catalyzed intramolecular [3 + 2] cycloaddition. (A) Synthesis of (−)-lingzhiol (17) [49]. (B) Synthesis of lycojaponicumin C (18) [58]. (C) Synthesis of sinensilactam A (20) [59]. (A) Platinum(II)-catalyzed

• mechanism. (C) The completion of total synthesis of kopsanone (19). (A) Synthesis of phyllocladanol (21) features a Lewis acid-catalyzed formal intramolecular [3 + 2] cross-cycloaddition of cyclopropane 1,1-diesters with alkenes [68]. (B) (5,6-Dihydro-1,4-dithiin-2-yl)methanol 151 used as a versatile allyl

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• with their complex structure, a number of total syntheses have been reported. This review will compare the synthetic strategies reported through the end of 2019. Keywords: antiproliferative; polyketide natural products; tetrahydropyrans; total synthesis; Introduction The spliceostatins/thailanstatins

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• the regiochemistry for terminal alkynes, affording the products substituted at the β-position. This regiochemistry switch might be regarded as the Holy Grail in Pauson–Khand chemistry. The synthetic potential of this methodology was demonstrated by the formal total synthesis of α-cuparenone [74][75

• intermediate in the total synthesis of α-cuparenone. Effect of the olefin partner in the regioselectivity of the PKR with trifluoromethyl alkynes [79]. Intermolecular PKR of trifluoromethylalkynes with 2-norbornene reported by the group of Konno [54]. Intermolecular PKR of diarylalkynes with 2-norbornene

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• applications in total synthesis, medium- and large-ring syntheses, and conjugate diene isomerization processes. In 2006, Crimmins successfully used this isomerization method in the syntheses of ophirin B and astrogorgin (Scheme 25) [31]. In the reaction, the intermediate 70 reacts with

• presence of PhSSPh, the new isomer 73 could also be converted to the desired (E,E)-isomer 71. In the total synthesis of the macrocyclic antibiotic antitumor agent (+)-hitachimycin, Smith used a disulfide-catalyzed isomerization [32] to synthesize the intermediate 75 with an E-configuration, which was

• disulfide-catalyzed enantioselective synthesis of ophirin B. Disulfide-catalyzed isomerization in the total synthesis of (+)-hitachimycin. Disulfide-catalyzed isomerization in the synthesis of (−)-gloeosporone. Acknowledgements I thank Prof. Xiao Wang (Nanjing University) for helpful discussions. Funding I

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• intermediate for the total synthesis of sesquiterpene thioalkaloids (Scheme 3). Spiro[3.3]heptane derivatives were recently used as the surrogates of piperazines, piperidines, morpholines, and thiomorpholines, which display pharmacological activities [35]. 1,6-Thiazaspiro[3.3]heptane (24) was synthesized for

• starting material was converted into bis(hydroxymethyl)quinolizidinone 56. After mesylation and the double displacement with sodium sulfide, spirothietane-quinolizidine 57 was obtained as a key intermediate. It was further applied in the total synthesis of four different natural products of Nuphar

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• the total synthesis of the natural product (+)-myrtine with 14% overall yield (Scheme 1B) [17]. For this application, the highest yield (73%) and enantioselectivity (96% ee) were obtained using the chiral ligand L3 and a copper salt as the catalyst. Despite the fact that examples of high yield and

• this reaction, in most cases providing the products with a high enantioselectivity and a moderate yield. An exception was found with diisopropylzinc, for which only 56% ee could be obtained. The methodology was also successfully applied to the total synthesis of the natural alkaloid (R)-coniine

• , and future developments in substrate and organometallics scope can be expected. Copper-catalysed ACA of organometallics to piperidones. A) addition of organozinc reagents; B) addition of organoaluminium reagent in the total synthesis of (+)-myrtine; C) addition of Grignard reagents. Copper-catalysed

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• group total synthesis of (–)-oxycodone. Biomimetic syntheses of rhodonoids A, B, E, and F. α-Photooxygenation of chiral aldehydes. Asymmetric photooxidation of indanone β-keto esters by singlet oxygen using PTC as a chiral inducer, and the related mechanism. Asymmetric photooxidation of both β-keto

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• metathesis in tandem with a diene cross-metathesis as the crucial steps were reported by Lee in the total synthesis of (−)-amphidinolide E (3) (Scheme 6) [70]. It is noteworthy that the second-generation Grubbs catalyst was quite active and stereoselective for both the enyne and cross-metathesis steps

• complexity, by essentially using a Ru-catalyzed alkene–alkyne (Ru-AA) coupling reaction and a macrolactonization step (Scheme 8). In this carefully designed total synthesis, after applying a Marshall coupling reaction aimed at installing a propargyl group into the initial acetylene component, an enyne

• -metal-catalyzed transformations were needed to achieve the total synthesis of des-epoxy-amphidinolide N, including a palladium asymmetric allylic alkylation (Pd-AAA), a Mukaiyama aldol reaction (with Sn), and a Krische allylation (with Ir) [72]. As special feature of this procedure, an Evans aldol

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• either an anthryl or naphthyl group, the use of which led to moderate to good enantioselectivities in most cases. An application of this method is shown for the total synthesis of the natural product (+)-blastmycinone (Scheme 24). As a follow up to this work, the same authors successfully accomplished

• . Interestingly, this protocol was applied to the total synthesis of (R)-oxiracetam (142), a drug used for the treatment of Alzheimer’s disease [61]. In a similar way, a ligand-free, intramolecular silylarylation of unsaturated amides 143 could be performed, albeit following a radical pathway leading to cyclic

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

Absolute configurations of talaromycones A and B, α-diversonolic ester, and aspergillusone B from endophytic Talaromyces sp. ECN211

• Ken-ichi Nakashima,
• Junko Tomida,
• Takao Hirai,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 290–296, doi:10.3762/bjoc.16.28

• were presented. Furthermore, Nicolaou and Li introduced a means by which the absolute configuration can be determined from the total synthesis of α-diversonolic ester (3) [5]. However, to the best of our knowledge, data that enabled the determination of the absolute configuration has not been published

• esters [3], and globosuxanthone B [4], among others. Diversonolic esters were firstly reported by Holker from cultures of Talaromyces diversus, anamorph Penicillium diversum [3]; however, the originally proposed structures of the diversonolic esters were revised after 25 years, following their total

• synthesis [5]. Furthermore, the compound with the originally proposed structure of β-diversonolic ester had already been isolated as blennolide C from the fungus Blennoria sp. prior to structural revision [2]. Consequently, the structures and spectroscopic data of the diversonolic esters and blennolide C