Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• /ketalization cascades of generated (S)-34 proceeded predominantly, achieving the chemoenzymatic total synthesis of trichodimerol (2) in 27% yield from 33. In contrast, the use of acetone as the co-solvent resulted in the homodimerization of (S)-34 via Diels–Alder reaction between the cyclohexadienone moieties

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• suppress homodimerization, via a stepwise (3 + 2) cycloaddition of the initially generated cumyl cation across the olefin in amylene. Our group became intrigued by the potential of dihydrodithiins to act as carbocation-stabilizing groups, as these would represent a synthetic equivalent of ‘naked’ allyl

• the (3 + 2) cycloaddition pathway under simple acid-promoted conditions, without notable problems of styrene oligomerization or homodimerization. The method allowed a short racemic total synthesis of the sesquiterpenoid cuparene (±-98, Scheme 14d), wherein the synthetic challenge of the contiguous

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• ester acted as an ideal radical precursor and accepted a single electron from the excited state CuI-acetylide complex. The copper catalyst plays a dual role, namely, as a photoredox catalyst and a cross-coupling catalyst. NHP-type esters inhibited the homodimerization of the alkyl radical and terminal

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

• 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

• corresponding homodimers for novel secondary metathesis reactions [44]. Thus, olefins can be categorized as type I (fast homodimerization), type II (slow homodimerization), type III (no homodimerization) and type IV (unreactive olefins, spectators to CM) [44]. Although olefins with perfluorinated alkane moiety

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• side-chain hydroxylation modifications (series iii), with macrocycle ring-size variations (series iv), and with macrocycle homodimerization (series v). We systematically screened the ring-open and ring-closed photoforms of all 29 compounds in vitro, using a range of cellular toxicity assays (against

• the ring-closed and ring-opened isomers, we can presume that homodimerization may affect the way in which the peptides interact with their molecular targets, or it may compromise their long-term biostability. Likewise, an elongation of the β-sheet core and an increase in cationic charge density

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• species could be also involved mechanistically in the Ag-mediated reaction of enynals with conjugated dienes [18] and the homodimerization of enynals [19][20]. So, the studies on the reactions of alkynes involving the generation of silver carbene species from non-diazo precursors are of great value for

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

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

• all functional groups. Commercially available vinylsilsesquioxanes can be easily modified and/or functionalized by cross metathesis. According to the CM product-selectivity model [56], vinylsilsesquioxane is an olefin type III (it does not undergo homodimerization). The correct choice of olefin and

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

• derivatives, belonging to class-I olefins according to Grubbs’ generalizations [31], are indeed known to be a sluggish partner in CM reactions, with homodimerization to stilbene being a recurring problem. Alkenes 4h–j containing a benzyl ester functionality at two, three and four carbons apart, respectively

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

• reactions a 1:3 ratio of A/B was applied. Practical limitations are that A and B have to be of significantly different polarity for easy column chromatographic separation and that sterically hindered olefins are not tolerated. For some alkenes, e.g., styrenes, the homodimerization is too fast leading to

Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor in Salmonella enterica serovar Typhimurium

• Matthew J. Styles and
• Helen E. Blackwell

Beilstein J. Org. Chem. 2018, 14, 2651–2664, doi:10.3762/bjoc.14.243

• sufficiently high to productively bind to the LuxR-type receptor protein. AHL binding typically promotes receptor homodimerization and binding to DNA at various promoters to activate transcription of QS-controlled genes, often including luxI and luxR (thereby autoinducing the QS system). B) Compounds

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• of a hexameric [TLR4∙MD-2–LPS]2 complex (Figure 3A). LPS-induced homodimerization of TLR4∙MD-2–LPS complexes provokes the recruitment of adaptor proteins to the cytoplasmic TIR (Toll/interleukin-1 receptor) domains of TLR4 which eventually results in the induction of the intracellular pro

• diglucosamine backbone [101][102]. The absence of the 1-phosphate group on the MPLA molecule weakens the efficiency of the homodimerization of two TLR4·MD-2-ligand complexes which results in a weaker cytokine inducing capacity, diminished immune activation and lower endotoxic activity, while retaining

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• high desolvation penalties and constrainment of flexible loop motifs which together contribute to a significant energy penalty upon binding. Nonetheless, these qualities enable ligand promiscuity and can facilitate other features such as the inactivation via homodimerization as exemplified in BDCA-2

• 0.3 Å). B) The binding site of A exhibits a flexible loop which enables homodimerization (chain A in green and chain B in magenta), in which a glutamate residue that is essential for Ca2+ binding ends up projecting away from the binding site (illustrated for chain A). The situation is mirrored for

High-speed vibration-milling-promoted synthesis of symmetrical frameworks containing two or three pyrrole units

• Marco Leonardi,
• Mercedes Villacampa and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2017, 13, 1957–1962, doi:10.3762/bjoc.13.190

• achieved by a different approach involving the homodimerization of 1-allyl- or 1-homoallylpyrroles by application of cross-metathesis chemistry. Keywords: diversity-oriented synthesis; mechanochemistry; multicomponent reactions; pyrroles; solvent-free synthesis; Introduction Symmetrical molecules formed

• fragments, we briefly examined the homodimerization reactions of 2-allyl- and 2-homoallylpyrroles via cross-metathesis, which should give access to spacers not easily accessible by the previously described route. The starting materials for this study (compounds 11) were readily prepared under the conditions

• a double bond in their spacer chain were obtained by a different approach involving the homodimerization of 1-allyl- or 1-homoallylpyrroles by cross-metathesis. Scope of the synthesis of symmetrical bispyrrole derivatives. Our synthetic planning and structural diversity of starting materials

A cross-metathesis approach to novel pantothenamide derivatives

• Jinming Guan,
• Matthew Hachey,
• Lekha Puri,
• Vanessa Howieson,
• Kevin J. Saliba and
• Karine Auclair

Beilstein J. Org. Chem. 2016, 12, 963–968, doi:10.3762/bjoc.12.95

• . Metathesis reaction optimization In 2003, Grubbs published a classification system for cross-metathesis catalysts and substrates, defining the substrates by type ranging from I to IV depending on their level of homodimerization observed in a metathesis reaction [20]. Type I substrates are defined as

• resulting in fast homodimerization under the conditions of the reaction. Such substrates include terminal alkenes of low steric bulk. Type II and type III substrates, with the latter being bulkier, show slow or no detectable homodimerization, respectively. Type IV is a separate class, including substrates

• that are spectators to metathesis yet do not inactivate the catalyst. It has been shown that for optimal results (minimal homodimerization) the two olefins to undergo cross-metathesis should be of different types [20]. The two intermediates selected as possible reactants, compounds 8 and 9, were

Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems

• Kirk W. Shimkin and
• Donald A. Watson

Beilstein J. Org. Chem. 2015, 11, 2278–2288, doi:10.3762/bjoc.11.248

• , evidence suggests that radical intermediates are involved in the bond forming step (Scheme 5). For instance, bibenzyl byproducts were observed in the cross-coupling of benzyl halides, suggesting a homodimerization of benzylic radicals. The reaction does not proceed in the presence of radical scavengers

Cross-metathesis reaction of α- and β-vinyl C-glycosides with alkenes

• Ivan Šnajdr,
• Kamil Parkan,
• Filip Hessler and
• Martin Kotora

Beilstein J. Org. Chem. 2015, 11, 1392–1397, doi:10.3762/bjoc.11.150

• homodimerization of the starting alkenes 2 and 8 has not been observed under the reaction conditions used (however, we cannot exclude that minor undetected amounts of homodimers of 2 or 8 were formed), they could be preliminarily considered as type II or III olefins according to the Grubbs classification of

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• ][69][70]. In fact, the binding of BMP can induce different signaling cascades. Either the ligand binds to a preformed complex (PFC) consisting of a type I and II receptor, or the ligand mediates homodimerization of BMPR-I, followed by recruitment of BMPR-II (Figure 5b). The latter oligomerization mode

Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• -libraries of homo- and heterodimers verified by ESI-MS and HPLC. In a preliminary evaluation, some compounds display moderate activity against the Gram-positive bacterium Bacillus subtilis. Keywords: antibacterial; combinatorial; diynes; homodimerization; multicomponent reactions; peptoids; Ugi reaction

• development of a combinatorial version of the copper-catalysed homodimerization. In this strategy two or more alkyne peptoids should couple simultaneously in the same reaction vessel in order to generate small libraries of dimers. In contrast to parallel synthesis, the combinatorial approach easily generates

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• ), and substrates with bulky substituents were not well tolerated, giving low yields or ee. Notably, the reactions proved that MBH carbonates can serve as one-carbon synthons for the annulations and expanded the utility of MBH carbonates in synthetic chemistry. 2.11 Annulations through homodimerization

• of ketoketenes Using the chiral catalysts (S,Rp)-Josiphos F5 and F6, the Kerrigan group developed the asymmetric homodimerization of ketenes (Scheme 49) [92]. This self-condensation of ketoketenes proceeded in dichloromethane at –25 °C to give chiral β-lactones in high yields (up to 99%) with good to

The catalytic performance of Ru–NHC alkylidene complexes: PCy₃ versus pyridine as the dissociating ligand

• Stefan Krehl,
• Diana Geißler,
• Sylvia Hauke,
• Oliver Kunz,
• Lucia Staude and
• Bernd Schmidt

Beilstein J. Org. Chem. 2010, 6, 1188–1198, doi:10.3762/bjoc.6.136

• reactions than for ring closing acrylate metathesis reactions. However, the remarkably high amount of homodimerization product 7b points to considerable activity of H in cross metathesis reactions, a peculiarity which has previously been noted for the bis(pyridine) complex G [33][34][35]. Cross metathesis

• ]. Therefore, 8 can be considered as a rather challenging substrate. As partners in the cross metathesis reactions, three acrylates 9a–c were chosen. In addition, homodimerization of 8 to diol 11 was also investigated (Scheme 4). The results are summarized in Table 4. With methyl acrylate 9a in dichloromethane

A thermally-induced, tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition approach to carbocyclic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2010, 6, No. 33, doi:10.3762/bjoc.6.33

• spirocyclobutanes that are accessed via alkylation chemistry [5]. Alternatively, more structurally complex spirocyclobutanes have been obtained from homodimerization reactions of allenes or alkenes [6][7]. However, neither of these approaches provides an enabling strategy for accessing the densely functionalized