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

• , they established a preparative-scale approach toward the pikromycins family and their aglycones in 2013 [70]. The preparation of activated pentaketides (37) using asymmetric α-alkylation and cross metathesis as key reactions reduced the step counts from 14 to 11 steps. Replacing the extender unit from

• epoxidation with enzymatic macrocyclization in 2020 as shown in Scheme 8 [85]. According to their previous report [86], the production of fragments 61 was initiated by Evans’ asymmetric aldol and alcohol protection to generate 57. Six-step route transformations, including cross metathesis, afforded aldehyde

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• significantly. One of the new and budding directions in recent years is the stereoselective olefin metathesis processes based on catalysis by complexes of molybdenum, tungsten and ruthenium [3][4][5]. The first publications have recently appeared that molybdenum complexes can catalyze cross-metathesis of butene

• 1b. Wherein various alkyl and aryl olefins, including those that contain Lewis basic esters, carbamates and amines or α-branched moieties, may be used in efficient and exceptionally Z-selective cross-metathesis reactions [6][7][8]. A few years ago, some publications devoted to the cleavage of the C–F

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

• . Despite the relative simplicity of substrate 99, the reaction was running in the exclusive presence of G-II catalyst and necessitated a high catalyst loading (30 mol %) to eventually furnish modest yields. The presence of two major byproducts was also noticed, namely the cross metathesis adduct resulting

• from 2 equivalents of 99 and the cross metathesis adduct resulting from 99 and a styrene unit coming from the catalyst. In addition, the corresponding RCM on the alkene analogue of 99 did not proceed either with G-II or Schrock catalysts, showcasing the substrate sensitivity of this reaction. 1.3

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

• the removal of metathesis catalysts is the formation of Ru-DMSO complexes, which do not eluate from a silica column [56]. This allowed us to remove at least the Ru contamination, but we were unable to subject 12 to further modifications such as cross metathesis or thiol-ene click reactions due to poor

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

• -promoted double bond migration. The cyclopropyl functionality in 46 can be assembled from the reaction of sulfur ylide and the α,β-unsaturated ketone 47, which in turn can be realized from the cross metathesis between commercially available ethyl vinyl ketone (48) and the C2-symmetrical diene-diol 49. The

• synthesis commenced with the monoprotection of the known diene-diol ent-49 as TBS ether affording compound 50 in 76% yield, which served as an excellent strategy to direct the later cross metathesis reaction to one site of the olefin over another (Scheme 5). Thus, the desired α,β-unsaturated ester 51 was

• compound 82. This molecule is expected to be available from cross metathesis of olefins 83 and 84. These two intermediates can then be readily prepared from optically active oxirane 85 and its enantiomer which can be derived through the Sharpless epoxidation of penta-1,4-dien-3-ol (86). In the synthesis

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

• Abstract This work presents an examination of the selective functionalization of norbornadiene through nitrile oxide 1,3-dipolar cycloaddition/ring-opening metathesis (ROM)/cross-metathesis (CM) protocols. Functionalization of commercially available norbornadiene provided novel bicyclic scaffolds with

• ; 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

• general model suitable for the prediction of product selectivity and olefin bond chemodifferentiation in cross metathesis. In general, regarding the reactivity of the olefin bond in CM, alkenes can be categorized by the relative ability to undergo homodimerization via CM and the possibility of the

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

• products were obtained after four additional steps: cross-metathesis of allylated compounds 120 with methyl vinyl ketone, reduction of conjugated C=C double bond, removal of the sulfinyl group under acidic conditions, and final stereoselective reduction of the imine formed by intramolecular cyclization

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• formal synthesis of inthomycin C ((−)-3). In 2018, Donohoe et al. demonstrated a tin-free, short and efficient total synthesis of inthomycin C ((−)-3) by comprising the three key steps of C−C bond-forming reactions: i) a vinylogous Mukaiyama aldol reaction, ii) an olefin cross-metathesis reaction, and

• ((−)-3). Synthesis of the cross-metathesis precursors (rac)-118 and 121. Donohoe’s total synthesis of inthomycin C ((−)-3). Synthesis of dienylboronic ester (E,E)-128. Synthesis of the alkenyl iodides (Z)- and (E)-130. Burton’s total synthesis of inthomycin B ((+)-2). Burton’s total synthesis of

• vinylogous Mukaiyama aldol reaction to produce the desired aldehyde (rac)-118 in 81% yield. Meanwhile, the TIPS protection of oxazole 119 and then subsequent lithiation at the C-5 position and quenching in situ with allyl bromide furnished oxazole derivative 121 in 90% yield (Scheme 16). An attempted cross

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

• 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

• ethene atmosphere were applied in the reaction. In contrast to G-I, the presence of an ethene atmosphere was highly detrimental for the RCEYM catalyzed by the more stable and active G-II and HG-II precatalysts, as this led to the intermolecular cross-metathesis between the triple bonds of the substrates

• that a ruthenium-containing metathesis intermediate, formed by the alkene cross metathesis in the initiating step followed by a RCEYM, was deactivated by a subsequent reaction with the triple bond of the second enyne molecule. The results of the RCEYM of the ester-modified oxaenediyne 2e were

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• yield and high enantioselectivity (Scheme 7) [15][16]. The Achmatowicz oxidation and ionic reduction generated the enone 58, which is regioisomeric with 53. The 1,4-addition of lithium dimethylcopper gave the desired cis-55 with high a diastereoselectivity (25:1). The cross-metathesis of 55 with 3

• generate the mixed cyclic ketal 120. Finally, the removal of the C-4’ silyl protecting group, acylation of the resultant alcohol, removal of the C-4 silyl protecting group, and ketal hydrolysis generated FR901464 (1). Fragment coupling via olefin cross-metathesis Koide’s group was the first to demonstrate

• the use of a Ru-catalyzed olefin cross-metathesis for the generation of the dienyl segment joining the two tetrahydropyranyl segments (Scheme 20) [12][13]. The cleavage of the Boc amide of 31 and the eventual amidation with (2Z,4S)-4-acetoxy-2-butenoic acid (12c) gave 121. The construction of the

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

• pyrrolobenzodiazepine structure, Mori et al. [76] successfully combined an enyne metathesis and an alkene cross-metathesis in an efficient sequential manner under the action of both the Grubbs first-generation and Hoveyda–Grubbs second-generation catalysts. According to this procedure, initially an enyne precursor was

• , which underwent a cross-metathesis with ethyl acrylate in the presence of the Hoveyda–Grubbs second-generation-type catalyst (10 mol %) leading to the corresponding vinyl ester 8 in 63% yield, as a convenient precursor to (+)-anthramycin. The latter was obtained via an isomerization of the double bond

α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

• Shital K. Chattopadhyay,
• Subhankar Ghosh,
• Sarita Sarkar and
• Kakali Bhadra

Beilstein J. Org. Chem. 2019, 15, 2524–2533, doi:10.3762/bjoc.15.245

• the important anticancer drug suberoylanilide hydroxamic acid (SAHA) from its α,ß-didehydro derivative is described. The didehydro derivative is obtained through a cross metathesis reaction between a suitable terminal alkene and N-benzyloxyacrylamide. Some of the didehydro derivatives of SAHA were

• species (ROS) as some apoptotic features. Keywords: anticancer drug; cross metathesis; HDAC inhibition; hydroxamates; reactive oxygen species; Introduction Suberoylanilide hydroxamic acid (SAHA, 1, Figure 1, vorinostat [1][2], has now emerged as a FDA approved drug for the treatment of relapsed and

• ,ß-dehydro-SAHA derivatives relied on the identification that a successful cross metathesis between anilide 7a (Scheme 1) containing a terminal double bond and N-benzyloxyacrylamide (8) may provide access to α,ß-dehydro-SAHA derivative 10a, which may serve as precursor of both SAHA and its dehydro

Hoveyda–Grubbs catalysts with an N→Ru coordinate bond in a six-membered ring. Synthesis of stable, industrially scalable, highly efficient ruthenium metathesis catalysts and 2-vinylbenzylamine ligands as their precursors

• Kirill B. Polyanskii,
• Kseniia A. Alekseeva,
• Pavel V. Raspertov,
• Pavel A. Kumandin,
• Eugeniya V. Nikitina,
• Atash V. Gurbanov and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2019, 15, 769–779, doi:10.3762/bjoc.15.73

• by NMR, ESIMS, and X-ray crystallography. The utility of this chemistry is further demonstrated by the tests of the novel catalysts (up to 10−2 mol %) in different metathesis reactions such as cross metathesis (CM), ring-closing metathesis (RCM) and ring-opening cross metathesis (ROCM). Keywords: CM

• ; cross metathesis; Hoveyda–Grubbs catalyst; olefin metathesis; RCM; ring-closing metathesis; ring-opening cross metathesis; ROCM; ruthenium metathesis catalyst; styrene; 2-vinylbenzylamine; Introduction Ruthenium-catalysed olefin metathesis reactions have been playing an important role in various fields

• ][9][10][11][12], including most popular recent books [13][14]. Obviously, the application of various catalysts is required to achieve the best results in each of the many directions of metathesis reactions such as cross metathesis – CM, ring-opening metathesis – ROM, ring-closing metathesis – RCM

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• . In most cases, the C2–C3 bond was formed by Ireland-, Johnson-, or Eschenmoser–Claisen rearrangement [10][11][12][13][14][15][16][17]. Alternatively, Evans methodology has been used [18][19][20]. The central C4–C5 double bond has also been constructed by Wittig reaction, cross metathesis, and ring

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• ). In the ROMP of the norbornene derivative 13, ArM 6 and ArM 7 performed best, outperforming catalyst 9. A near ten-fold increase is observed for ArM 6 (Table 10, entry 2). In the cross metathesis of terminal olefins 73, 74, and 75, with the commercial catalyst 9 conversions of 79%, 98% and 94

• allyl-sulfide on the surface of the protein. Cross metathesis of the modified protein 82 with allyl alcohol gave the CM product with over 90% conversion (Scheme 18). To achieve this challenging reaction, 200 equivalents (equiv) of HG-II catalyst were employed in a reaction mixture containing 0.01 mM 82

• for cross metathesis with allyl alcohol or with a fluorescein derivative (Scheme 19a). To further advance the chemical tagging through cross metathesis, genetic incorporation of Ahc was performed in human cells (HEK 293T) for the modification of the Fc region of IgG (IgG-Fc-Ahc32, Scheme 19b). An

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• silsesquioxanes (POSS) and POSS-containing polymeric materials. Three types of processes, i.e., cross metathesis (CM) of vinyl-substituted POSS with terminal olefins, acyclic diene metathesis (ADMET) copolymerization of divinyl-substituted POSS with α,ω-dienes and ring-opening metathesis polymerization (ROMP) of

• metathesis in chemistry of unsaturated derivatives of POSS is limited to three types of processes, i.e., cross metathesis (CM) of vinyl-substituted POSS with terminal olefins, acyclic diene metathesis (ADMET) copolymerization of divinyl-substituted POSS with α,ω-dienes and ring-opening metathesis

• application of molybdenum-based complexes in modification of silsesquioxanes (Figure 3), which can be explained as related to the sensitivity of these complexes toward atmospheric oxygen, moisture and functional groups of reagents. Review Cross metathesis of vinyl-substituted silsesquioxanes The first

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• across double C=C bonds. The main techniques, actively developed during the last decade and discussed here, are the coupling of end-functionalized blocks, sequential ring-opening metathesis polymerization, and cross metathesis between unsaturated polymers, or macromolecular cross metathesis. The last

• . Keywords: ADMET; macromolecular cross metathesis; multiblock copolymers; olefin metathesis; ROMP; Introduction Nowadays, olefin metathesis has become a well-established field of organic and polymer chemistry. The discovery of metallocarbene initiators that are capable of catalyzing metathesis

• -functionalized blocks, and macromolecular cross metathesis. Review Synthesis by sequential ring-opening metathesis polymerization Living ring-opening metathesis polymerization (ROMP) provides an opportunity to use a well-established route to multiblock copolymers based on the repetitive addition of different

Catalysis of linear alkene metathesis by Grubbs-type ruthenium alkylidene complexes containing hemilabile α,α-diphenyl-(monosubstituted-pyridin-2-yl)methanolato ligands

• Tegene T. Tole,
• Johan H. L. Jordaan and
• Hermanus C. M. Vosloo

Beilstein J. Org. Chem. 2019, 15, 194–209, doi:10.3762/bjoc.15.19

• (RCM) of dialkenes, ring-opening metathesis polymerisation (ROMP), isomerisation of alkenes and cross-metathesis (CM) of alkenes [7]. The complexes were synthesized by reacting the lithium salts of the corresponding pyridinyl alcohols with [RuCl2(=CHC6H5)(P(iPr3))2]. These complexes catalysed inter

Ammonium-tagged ruthenium-based catalysts for olefin metathesis in aqueous media under ultrasound and microwave irradiation

• Łukasz Gułajski,
• Andrzej Tracz,
• Katarzyna Urbaniak,
• Stefan J. Czarnocki,
• Michał Bieniek and
• Tomasz K. Olszewski

Beilstein J. Org. Chem. 2019, 15, 160–166, doi:10.3762/bjoc.15.16

• , the cross metathesis (CM) between alcohol 8 and the electron-deficient cross partner methyl acrylate (10, Table 1). All reactions were run at 36 °C in D2O promoted either by microwave (µW) or ultrasound (US) irradiation, and for comparison purposes also with standard magnetic stirring. In the case of

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• catalysts 61, 64, 65, 67 and 68 (Figure 16) were also investigated in the model asymmetric ring-opening cross metathesis (AROCM) of cis-5-norbornene-endo-2,3-dicarboxylic anhydride (75) with styrene (Scheme 8, Table 3) [32]. In this reaction complex 68 showed the highest selectivity for the formation of the

Cross metathesis-mediated synthesis of hydroxamic acid derivatives

• Shital Kumar Chattopadhyay,
• Subhankar Ghosh and
• Suman Sil

Beilstein J. Org. Chem. 2018, 14, 3070–3075, doi:10.3762/bjoc.14.285

• Shital Kumar Chattopadhyay Subhankar Ghosh Suman Sil Department of Chemistry, University of Kalyani, Kalyani - 741235, West Bengal, India, Fax: +91+33+25828282 10.3762/bjoc.14.285 Abstract An alternative synthesis of α,ß-unsaturated hydroxamates via cross metathesis between a class-I olefin and N

• important demonstration of the protocol is the preparation of the unusual amino acid component of the bioactive cyclic peptide Chap-31. Keywords: α-amino acid; catalysis; cross metathesis; hydroxamates; Introduction Cross-metathesis reactions (CM) have rapidly grown [1][2][3] to be a reliable method for

• CM-mediated synthesis of functionalized alkenes of various kinds continue to appear. For example, cross metathesis with acrylates [8][9][10], α,ß-unsaturated acid chlorides [11], acrylamides [12][13][14], vinyl sulfones [15], vinylphosphine oxides [16], vinyl phosphonates [17], enones [18], and

A tutorial review of stereoretentive olefin metathesis based on ruthenium dithiolate catalysts

• Daniel S. Müller,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2018, 14, 2999–3010, doi:10.3762/bjoc.14.279

• ), ring-opening/cross metathesis (ROCM), cross metathesis (CM), self-metathesis and ring-closing metathesis (RCM) reactions. Scheme 2 and Scheme 3 display selected examples for each of these reactions [1]. ROMP is one of the most facile metathesis reactions, thus allowing for very low catalyst loadings

• noted that very recently Grubbs and Choi employed Ru-3 for highly β-selective cyclopolymerization (not depicted in this review) [18]. Cross metathesis with cis-butendiol 12 was extensively explored by Hoveyda (Scheme 2c) [4]. The synthesis of Z-configured allylic alcohols is particularly attractive from

• the synthetic point of view. Allylic alcohols are highly versatile entities in organic chemistry and serve as starting materials in a multitude of reactions such as allylic substitutions [19]. Another advantage of this particular cross metathesis is that stereochemically pure cis-butenediol is

MoO₃ on zeolites MCM-22, MCM-56 and 2D-MFI as catalysts for 1-octene metathesis

• Hynek Balcar,
• Martin Kubů,
• Naděžda Žilková and
• Mariya Shamzhy

Beilstein J. Org. Chem. 2018, 14, 2931–2939, doi:10.3762/bjoc.14.272

• ‘ acidity and accessibility of the catalytic species on the surface. On the other hand the supports‘ acidity decreases the selectivity to the main metathesis product C14 due to an acid-catalyzed double bond isomerization (followed by cross metathesis) and oligomerization. 6MoO3/2D-MFI(26) with a lower

• of these materials have been tested as supports for MoO3 based catalysts for metathesis of higher alkenes up to now. MoOx on MCM-22 combined with γ-Al2O3 was used in cross metathesis of 2-butene and ethylene in a stream (125 °C, 1 MPa) [23]. MCM-22, and MCM-56 were also used as supports for Hoveyda

• in considerable amounts. It is a consequence of the 1-octene double bond isomerization followed by cross metathesis. Moreover, a certain amount of oligomers (mainly dimers) were also observed in the reaction mixtures. Both isomerization and oligomerization are due to the acidic character of the

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• . These transformations include all three fundamental olefin metathesis reactions: ring-opening metathesis polymerization (ROMP), ring-closing metathesis (RCM) as well as cross metathesis (CM) (Scheme 2). Review Artificial metatheases – anchoring approaches Metalloproteins that contain one or more metal

• Chauvin [2]. Right: Potential influence of the protein as second coordination sphere in the transition state that lead to different metathesis products. (i) Ring-opening metathesis polymerization (ROMP), (ii) ring-closing metathesis (RCM) and (iii) cross metathesis (CM). Biotinylated GH-type catalysts for