Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• pikromycin and the aglycones in this family, 10-deoxymethynolide (24) and norbonolide (25), using asymmetric aldol reaction, Yamaguchi esterification, and ring-closing metathesis as key steps [65][66]. Nevertheless, the inherent complexity of these natural products demands high step counts, leading to low

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• moderate to good yield (35–82%). 3.5 Ring-closing metathesis Olefin metathesis is a metal-catalysed reaction wherein carbon–carbon double bonds are cleaved and formed through an intermediate cyclometallacarbene 114, thus allowing for transalkylidenation and the formation of mixed alkenes 115 (Scheme 24

• ) [66]. Variations of this reaction include alkyne metathesis [67] and carbonyl metathesis [68]. Ring-closing metathesis (RCM) gave access to a series of dibenzo[b,f]heteropines, as reported by Matsuda and Sato [31] (Scheme 25). The authors synthesised a series of Si-, Sn-, Ge- and B-tethered dienes 118

• –Grubbs catalyst) catalysed ring-closing metathesis gave dibenzo[b,f]heteropines 122 in excellent yields (>80%). Unfortunately, the metathesis reaction required elevated temperatures (>100 °C) and dilute solutions to reduce unwanted self-metathesis competing with RCM. While excellent yields for

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• applied for the synthesis of seven to fourteen-membered phostam, phostone, and phostine derivatives. 1.1 Synthesis via C–C bond formation Most medium and large phostams, phostones, and phostines were prepared via C–C bond formation, especially via ring-closing metathesis (RCM). 1.1.1 Synthesis via C–C

• bond formation through RCM reaction: Ring-closing metathesis (RCM) is an efficient strategy for the construction of common to large cyclic compounds via the formation of a C=C bond [26], which can be further reduced to a C–C bond. To prepare phostam-derived antitumor agents, ethyl N-allyl-N-(but-3-en-1

• -azaphosphocin-1(4H)-yl)acetate (4), respectively, in the presence of the Grubbs first generation catalyst via ring closing metathesis. The products 3 and 4 were further transformed to antitumor agents 5, 6, 9 and 10 through aminolysis with O-TMS hydroxylamine or hydrogenolysis followed by aminolysis with O-TMS

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• following criteria: position/stage of the key cyclooctane ring formation in the synthesis plan, the selectivity, and the opportunity for late-stage functionalization. Review 1 Metathesis: ring-closing metathesis and related methods The metathesis reaction, first discovered by serendipity in the 1950s, has

• synthesis of five- and six-membered rings can be readily achieved through ring-closing metathesis (RCM), but the synthesis of eight-membered rings has been carried out later [13][14]. In this part, we will focus on the use of RCM to achieve total syntheses of natural products or to access the carbon

• skeleton of natural products, and more particularly to construct the cyclooctane ring that is part in these motifs. 1.1 Ring-closing metathesis (RCM) Among all metathesis reactions available in the chemist’s toolbox, ring-closing metathesis (RCM) is nowadays one of the most popular and has been used

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• -oxides 56a in 23% and 93 in 63% yields, respectively, showing the limited scope of the synthetic method (Scheme 17) [39]. Ring-closing metathesis (RCM) is an efficient strategy for the construction of cyclic compounds via the formation of a C=C bond [40][41], which can be reduced to the C–C bond. 2

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• ]. Therefore, Roberge, Fogg, and co-workers investigated the advantages of continuously stirred tank reactors (CSTR) and tube reactors in comparison to the corresponding batch reaction for the ring-closing metathesis of diene 58, producing macrocyclic olefin 60 (Scheme 14) [52]. Although, macrocycle 60 is not

• 20 min at 80 °C using 1 mol % of catalyst 59 [52]. Due to the fact that ethylene formed in the ring-closing metathesis can result in the formation of unstable ruthenium methylidene species, causing degeneration of the metathesis catalyst, the continuous removal of ethylene from the reaction mixture

• can be highly beneficial. Therefore, Skowerski and co-workers constructed a tube-in-tube reactor for the ring-closing metathesis of dienes 62 and 63 to macrocycles 65 or 66, respectively, mediated by ruthenium catalyst 64 (Scheme 15) [53]. The substrate and the catalyst are mixed in a Q-piece and

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• equivalents of the acyclic precursor (S)-46 were preorganized by a Ca template and catenation was achieved by two-fold ring closing metathesis. This reaction yielded catenane (S,S)-47 (14% yield, see Figure 12) together with the non-interlocked macrocycle (S,S)-48 (22% yield, for the structure see Figure 13

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

• compound, we decided to use the Cyl-1 amino acid backbone and introduce a double unsaturated side chain (Scheme 1). In principle, selective modifications at the two different double bonds (internal and terminal) should be possible. Ring-closing metathesis (RCM) should generate an allylglycine unit, which

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• stapling and the most prominent methodology was developed by the groups of Grubbs and Verdine using ring-closing metathesis (RCM) [4][5][6]. The optimised protocol for these so-called hydrocarbon-stapled peptides uses α-methyl-, α-alkenylglycines in a distance of i, i + 3/i + 4 for one helix turn or i, i

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

• –Smith cyclopropanation; Hyptis brevipes Poit; ring-closing metathesis; Introduction Hyptis brevipes Poit. is an invasive plant species belonging to the mint family Lamiaceae [1][2][3][4]. This plant has been reported to originate from tropical America but is now distributed broadly in other tropical

• followed by esterification with 3-butenoic acid (37) under Steglich conditions (Scheme 3). The resulting product 38 was isolated in 86% yield. A subsequent ring-closing metathesis reaction and DBU-assisted double bond migration then furnished the anticipated structure 39. The PMB functionality was removed

• acid (17) (Scheme 4). The β-hydroxy moiety in 44 can be installed via Sharpless dihydroxylation of the silyl enol ether derived from ketone 45. The 5,6-dihydro-α-pyrone group in ketone 45 is envisaged from protected diol 46 by the sequence of Mitsunobu esterification, ring-closing metathesis, and base

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• ; organofluorine chemistry; selectivity; Introduction Olefin metathesis is considered to be a powerful synthetic tool for the creation of olefin bonds [1]. Several types of metathesis reactions, such as ring-opening metathesis (ROM), cross-metathesis (CM), ring-closing metathesis (RCM) or ring-opening/cross

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• published in 2018, de Koning and co-workers reported a new methodology to synthesize the benzo[a]anthracene skeleton of angucycline derivatives 146 by using a multistep strategy based on Suzuki–Miyaura, isomerization, and ring-closing metathesis reactions (Scheme 33) [67]. The commercially available 2

• . AuCl-catalyzed double cyclization of diiodoethynylterphenyl compounds. Iodonium-induced electrophilic cyclization of terphenyl derivatives. Oxidative photocyclization of 1,3-distyrylbenzene derivatives. Oxidative cyclization of 2,3-diphenylnaphthalenes. Suzuki-Miyaura/isomerization/ring closing

• metathesis strategy to synthesize benz[a]anthracenes. Green synthesis of oxa-aza-benzo[a]anthracene and oxa-aza-phenanthrene derivatives. Triple benzannulation of substituted naphtalene via a 1,3,6-naphthotriyne synthetic equivalent. Zinc iodide-catalyzed Diels–Alder reactions with 1,3-dienes and aroyl

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• properties (absorption and emission) for these versatile systems has been revealed. Keywords: Clauson–Kaas reaction; heterocycles; ring-closing metathesis; truxene; Ullmann-type coupling; Van Leusen reaction; Introduction The two-dimensional phenylene-based π-conjugated star-shaped architectures has

• functional materials and the opportunities are now open. Herein, we have assembled diverse truxene scaffolds containing heterocyclic systems involving trimerization, ring-closing metathesis, Clauson–Kaas and Van Leusen reactions as vital steps. Moreover, we have revealed the preliminary photophysical

• -closing metathesis (RCM), Clauson–Kaas and Ullmann-type coupling reactions as key steps. Moreover, we have also assembled some other interesting heterocyclic systems possessing oxazole, imidazole, benzimidazole, and benzoxazole in the framework of truxene. Additionally, the preliminary photophysical

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

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

• number of classical methodologies have been used for their synthesis, in which the key step is the generation of the six-membered ring, including the aldol reaction, the reductive amination, Mannich reaction, ring closing metathesis, Diels–Alder reaction with imines as dienophiles, aza-Prins cyclization

• subsequent steps, including ring-closing metathesis [133], (−)-cermizine B (171) and (+)-serratezomine E (172) were obtained 57% and 72% yield, respectively (Scheme 43) [134][135]. Cyclizations involving a position in the attacking nucleophile Isosolenopsin (177) and solenopsin (178) are two isomeric

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

• products [1][2][3][4][5][6][7][8]. Prins and related cyclization reactions [9][10], hetero-Diels–Alder cyclization [11], cyclization onto epoxides [12], Petasis–Ferrier rearrangement [13], intramolecular oxa-Michael reactions [14], cyclization through oxidative C–H bond functionalization [15], ring-closing

• metathesis (RCM) [16], halo etherification [17], reductive etherification [18][19], and metal-mediated cyclization [20][21], etc. are the most frequent strategies utilized for THP ring construction (Scheme 1). Amongst all, the Prins reaction has proven as a powerful technique in the stereoselective synthesis

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• cosmetics [147]. The catalyst could be recycled, however, with reduced performance due to Pt nanoparticle oxidation. 3.1.2 Polybutadiene (PBD): Partial depolymerisation of 1,4-PBD (cis, trans, Mw 1800–500000 g⋅mol−1) was achieved by an unconventional tandem ring-opening–ring-closing metathesis route

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• ). Enantiospecific synthesis of TKM-38 For the enantiospecific synthesis of TKM-38, which uniquely bears an eight-membered azacycle as the ring C, we explored 1) the amino-protecting group and 2) the conditions for the cyclization of the medium-sized ring by ring-closing metathesis (RCM). Finally, the established

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• with a cleavage of the distal C–C bond. The reaction proceeded regioselectively and in high yields. There was no difference observed between cis and trans-isomers in terms of the reactivity and yields. The resultant dienes 129 were used in ring-closing metathesis reactions to furnish gem

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

• chemical ecology of Adalia bipunctata and the recent methodologies to obtain adaline (1), euphococcinine (2), and N-methyleuphococcinine (3). Keywords: 9-azabicyclo[3.3.1]nonane; Coccinelid beetles; dipolar cycloaddition; homotropane; ring-closing metathesis; Introduction Coccinellid beetles contain a

• (−)-48, in 88% yield, as a single diastereoisomer. Then, (−)-48 was treated with trimethyl orthoformate to provide formamide (−)-49, being converted to cis-2,6-dialkenylformamide (−)-50 by treatment with the Lindlar catalyst. (−)-50 underwent a ring-closing metathesis efficiently in the presence of the

• (−)-79a and (−)-79b, which were oxidized to enone (−)-80. The enone (−)-80 was subjected to ring-closing metathesis with Grubbs second-generation catalyst resulting in cyclic enone (−)-81 in 74% yield. (−)-81 was treated with phenylselenol to generate selenide 82 in high yield. The ozonolysis of 82 was

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

• 60% yield (74% yield, brsm). A two-step synthesis from 127 produced diene 128, which was subjected to ring-closing metathesis and subsequent Dess–Martin oxidation to give 129 in 63% yield over two steps. Tetracycle 130, which was prepared from 129 in one step, was converted to lycojaponicumin C (18

• and AIBN to a refluxing solution of cyclopropane 155 afforded 156 in 38% yield. It was subjected to cleavage of the Boc group followed by N-allylation to give 157 in 73% yield over two steps. A ring-closing metathesis of freshly prepared 157 was effected by the second generation Hoveyda–Grubbs (HG II

• of aldehyde 163 and isoprene (164) with Ni(acac)2 and diethylzinc [78] and then Dess–Martin oxidation gave a diene (not shown, 94% yield over two steps), which was subjected to ring-closing metathesis to give enone 165 in 85% yield. Isomerization of the freshly prepared 165 to more stable α,β

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• , ring-closing, metathesis, cycloadditions, radical reactions and microwave-assisted reactions [38][39][40]. In this work, we attempt to develop a greener, simpler, more efficient and recyclable system to synthesize arylpyridine derivatives. Initially, the reaction of acetophenone (5a) and 1,3

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

• 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

• reactions of unsaturated compounds, e.g., alkene and enyne cross metathesis (CM [1] and EYCM [2][3][4]), alkene and enyne ring-closing metathesis (RCM and RCEYM) [5][6], ring-opening metathetic polymerization (ROMP) [7], etc., the CM and RCM are the most popular in organic synthesis [8]. Furthermore, the

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• catalyst 15 to yield the trimerized products 12 (syn) and 13 (anti) in respectable yields (Scheme 2). The alkene-bridge exchange of 12 (syn) was accomplished by tandem ring-opening and ring-closing metathesis (ROM–RCM) in the presence of Grubbs’ first generation (G-I) catalyst to generate a C3-symmetric

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• generation of the mixed acetal 113 (Scheme 18) [33]. A ring-closing metathesis gave an inseparable mixture of the dihydropyranyl ethers 114a and 14b, which could be equilibrated under acidic conditions (114b/114a > 20:1). A standard functional group manipulation afforded the vinyldihydropyran-2-one (−)-115

• hydrogenation over Pt2O and then low-temperature DIBAL reduction afforded the all-cis tetrasubstituted tetrahydropyran 27. In Koide et al.’s synthesis, the unsaturated lactone 29 was prepared via the Wittig methenylation of 24, followed by aminal hydrolysis, methallylation of the 2° alcohol 28, and ring-closing

• metathesis using Grubbs’ 2nd generation catalyst (G-II, Scheme 3) [13]. Replacing the N-Boc protecting group with an N-tosyl group and allylic oxidation gave 30. The introduction of the allyl group at C-11 made use of the Kishi protocol [22] of the allyl-Grignard addition, followed by an ionic reduction. The