On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• which parts are prone to oxidation/metabolization. A remarkable result, using diluted iodine, was actually reported recently [301]. Concerning another class of “old” drugs, and as depicted in Figure 9 with the (few) structures 49–61, the many generations of β-lactams used in human medicine is certainly

• various bacterial β-lactamases but still reactive (and selective) enough to form relatively stable covalent adducts with the bacterial DD-transpeptidases. The carboxylic or sulfonic moieties in these structures are instrumental in this regard. As seen in Figure 9, the rate of new β-lactams approved for

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• olefins 84 as nucleophile partners and racemic secondary and tertiary α-bromo-N-protected β-lactams 83 under nickel catalysis, along with the chiral bis(oxazoline) ligand 85 and triethoxysilane (Scheme 32) [108]. Substrate structural variations on 84 had only a small impact on the reaction

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

• pharmacy as highly biological active compounds. Among this group of nitrogenated heterocycles, β-lactams (azetidin-2-ones) have reached especial attention [78][79][80], being easily accessible from β-aminoesters. A stereoselective synthesis of 1-substituted 2-azaspiro[3.3]heptanes 45 (n = 1) was reported

• the asymmetric synthesis of a variety of aromatic, heteroaromatic, and aliphatic 1-substituted 2,6-diazaspiro[3.3]heptanes 48, with overall yields ranging from 74 to 94% (Scheme 16). Asymmetric synthesis of β–lactams β-Lactam antibiotics are important drug class of antibacterial agents [83] and in the

• successively into β-amino esters 51, and the corresponding β-lactams 52 with high optical purity (Scheme 17) [89]. The absolute configurations of compounds 52 were obtained by the comparison of the signs of specific rotation of 52 with R = Ph(CH2)2, with that of known (R)-4-(2-phenylethyl)azetidin-2-one. A 6/4

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• remedies [4]. β-Lactams (BL) have served as the first line antibiotics since the introduction of penicillin. However, due to existence and continuous increase in β-lactamases [5], multidrug therapy is becoming the new modality of bacterial treatment against multiple-drug resistant (MDR) bacteria. Multidrug

• passing through phase I and phase III clinical trials [6][25] in combination with different types of β-lactams. These multidrug combinations have shown promise for future antibiotic regime and drug development based on non-β-lactam inhibitors. Nonetheless, a partial loss of activity has been reported in

Recent synthesis of thietanes

• Jiaxi Xu

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

• tetracyclic fused benzoxazolethietane derivative 354 in 20% yield [83] (Scheme 69). In 1991, Sakomto and co-workers started on the synthesis of highly rigid thietane-fused β-lactams. They prepared various derivatives 356 in high yields via the photochemical cycloaddition reactions of N-(α,β-disubstituted

• ] cycloaddition. The reaction afforded the product in 70% yield with 40% ee at −45 °C and in 75% yield with 10% ee at 0 °C, respectively [97] (Scheme 71). One year later, they studied the diastereoselective synthesis of highly rigid thietane-fused β-lactams 358–361 from a chiral monothioimide 357. The

• performed the absolute asymmetric synthesis of highly rigid thietane-fused β-lactams 356 from achiral monothioimides 355 using a chiral crystal environment through a topochemically controlled intramolecular photochemical [2 + 2] cycloaddition in a benzene solution. Only the 2-methylacrylamide derivative

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

• Renata Kaczmarek,
• Dariusz Korczyński,
• James R. Green and
• Roman Dembinski

Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1

• intramolecular versions of the reaction are also highly successful [50][51]. Although the Nicholas reaction has been employed to functionalize biomolecules, including amino acids [52][53], β-lactams [54], steroids [55], and carbohydrates [56][57][58][59][60][61][62], we are unaware of any examples of nucleoside

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• identified. In addition, the development of new β-lactamase inhibitors is ongoing and may restore the activity of known β-lactams against β-lactamase-producing strains [2]. Unfortunately, most of these antibiotics rely on known modes of action and do not target novel binding sites. To circumvent established

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

• 2007, Feroci disclosed an electrochemical strategy for the cis-stereoselective synthesis of chiral β-lactams 180 via a 4-exo-tet cyclization of bromo amides 178 with an acidic methylene group and bearing a chiral auxiliary [101]. The cyclization occurred via deprotonation of the acidic methylene group

An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS,7aR,E)-2-ethyl-3-oxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-1-ylidene)sulfamoyl chloride

• Aytekin Köse,
• Aslı Ünal,
• Ertan Şahin,
• Uğur Bozkaya and
• Yunus Kara

Beilstein J. Org. Chem. 2019, 15, 931–936, doi:10.3762/bjoc.15.89

• reacts with unsaturated systems to yield either N-chlorosulfonyl-β-lactams 3 or unsaturated N-chlorosulfonyl amides 4 (Scheme 1). β-Lactams 3 generally predominate and in many cases are the exclusive products and they serve as key substances in a variety of chemical transformations. When chlorosulfonyl

Ring-opening metathesis of some strained bicyclic systems; stereocontrolled access to diolefinated saturated heterocycles with multiple stereogenic centers

• Zsanett Benke,
• Melinda Nonn,
• Márton Kardos,
• Santos Fustero and
• Loránd Kiss

Beilstein J. Org. Chem. 2018, 14, 2698–2707, doi:10.3762/bjoc.14.247

• transformations, cyclic dienes with different ring sizes might be considered to be important starting materials for the generation of structurally diverse molecules. Among the large number of possible transformations, the ring olefinic bond of alicyclic dienes may lead to valuable β-lactams [21][22][23] or γ

• Recently, we have demonstrated the high utility of various constrained cyclic dienes, such as norbornadiene as well as 1,5- and 1,3-cyclooctadienes in the context of their applicability towards the access of diverse, highly functionalized olefinated molecules [14][15][16]. The corresponding β-lactams

• derived from cyclodienes were used as starting substances for further functionalization with ROM. We have described a stereocontrolled synthetic route to access difunctionalized cyclic β-amino acid derivatives [14] and β-lactams [15][16] based on ring-opening metathesis (ROM) through ethenolysis of the

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• synthesis of spiro β-lactams via oxidative dearomatization reactions. In this report, the synthesis of spiro β-lactams 56 were achieved successfully by the oxidative cyclization of p-substituted phenols 55 using PIDA (15) as an electrophile and copper(II) sulfate pentahydrate as an additive in the presence

• (15). Iodine(III)-mediated spirocyclization of alkyl hydroxamates 50 to spirolactams 51 using stoichiometric amount of PIFA (31). PIFA-mediated cyclization of substrate 52 to spirocyclic product 54. Synthesis of spiro β-lactams 56 by oxidative coupling reaction of p-substituted phenols 55 using PIDA

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• under the reaction conditions to give directly the final chiral α-bromo-α-fluoro-β-lactams (3S,4R)-62a–k in moderate to high yields (53–90%) and high enantioselectivities (85–96% ee), as shown in Scheme 23. This method represented the first ligand-promoted aza-Reformatsky approach using a

• required to achieve at room temperature the corresponding chiral α,α-difluoro-β-lactams (R)-63a–h in moderate to good yields (45–76%) and high to excellent enantioselectivities (86–99% ee), as shown in Scheme 24. Using enantiomeric ligand (1S,2R)-59 under the same reaction conditions allowed the opposite

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• fused with β-lactams (Scheme 41) [56]. The competition between mono- and dichlorination remained an issue in these transformations; but fortunately, increasing the bulkiness of the ester group permitted to limit the reaction to the introduction of only one chlorine atom. It was also possible to achieve

• the isolation of similar compounds starting from differently substituted β-lactams, notably carrying a malonate moiety linked to the nitrogen [57]. More recently, CF3SO2Cl also found to be an appropriate reagent for the asymmetric introduction of a chlorine atom onto several substrates. For instance

• phenols. Mono- and dichlorination of carbon acids. Monochlorination of (N-aryl-N-hydroxy)acylacetamides. Examples of the synthesis of heterocycles fused with β-lactams through a chlorination/cyclisation process. Enantioselective chlorination of β-ketoesters and oxindoles. Enantioselective chlorination of

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• proteins against the activity of proteolytic enzymes [6][7], or are precursors of numerous active compounds such as β-lactams [8][9]. Finally, β-amino acids are present in numerous natural products [10]. These properties have generated great interest in the development of synthetic methods for the

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• (MAO) type B inhibitors [6] often used for the treatment of neuropsychiatric disorders such as Alzheimer’s and Parkinson diseases. These alkynylamines are also important building blocks for the synthesis of N-bearing compounds such as β-lactams [7][8], pyrroles [9], pyrrolidines [10], pyrrolophanes [11

β-Amino functionalization of cinnamic Weinreb amides in ionic liquid

• Yi-Ning Wang,
• Guo-Xiang Sun and
• Gang Qi

Beilstein J. Org. Chem. 2016, 12, 2372–2377, doi:10.3762/bjoc.12.231

• , but also in important building blocks widely used in the organic syntheses. They are especially used in the synthesis of β-amino acids [4][5], which are precursors for many biological and pharmacological active compounds, such as β-lactams [6] and β-peptides [7]. The most straightforward approach

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• also proceeded with high stereoselectivity because of the presence of a chiral nitroso agent. The regioselective nitroso hetero-Diels–Alder cycloaddition was also observed during the reaction of 3-dienyl-2-azetidinones 62 with nitrosobenzene (47), specifically providing 1,2-oxazine-substituted β

• -lactams 63 (Scheme 16) [95], which is in accordance with the general prediction. The exclusive regioselectivity of this reaction is due to steric effects. Similar conclusions result from the reaction of 1,3-butadienes 65 with various nitroso heterodienophiles 66, giving proximal isomer 67 (Scheme 17) [85

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• -1 Hirokoshingai, Kure, Hiroshima 737-0112, Japan 10.3762/bjoc.12.157 Abstract An effective synthesis for syn-β-lactams was achieved using a Rh-catalyzed reductive Mannich-type reaction. A rhodium–hydride complex (Rh–H) derived from diethylzinc (Et2Zn) and a Rh catalyst was used for the 1,4

• Mannich-type reactions have been reported to give β-amino esters and/or β-lactams by using metal enolates [10][11][12][13][14][15][16][17]. In contrast, most of reductive Mannich-type reactions using imines and α,β-unsaturated carbonyl compounds gave β-amino esters, but there are only a few reports for a

• direct synthesis of β-lactams by reductive Mannich-type reactions [14][18][19][20][21]. We recently reported a reductive Mannich-type reaction using a combination of RhCl(PPh3)3 and Et2Zn to give the corresponding syn-β-lactams from α,β-unsaturated esters and imines in good to excellent yields together

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• irradiation. Thus, the development of novel MCR based on phosphorous reagents would allow the synthesis of macrocyclic and medium or large-sized heterocyclic systems, substances which are currently underrepresented in the literature. Further, the design of new biocompatible scaffolds such as β-lactams and

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• ]. The scope of the anodic methoxylation has so far been limited to either acyclic or 4–6-membered ring sizes, the use of electrosynthetic approaches can also be applied to larger 7-membered ring systems, albeit less frequently [65][66]. β-Lactams (4-membered rings) undergo anodic oxidation of the carbon

Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

• Zsolt Szakonyi,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2014, 10, 2738–2742, doi:10.3762/bjoc.10.289

• obtained. These include the selective reduction of β-enamino ester enantiomers [14], enzyme-catalyzed kinetic resolution [15], and a variety of asymmetric syntheses, for example, the enantioselective syntheses of β-lactams followed by ring opening [16][17], or the enantioselective desymmetrization of

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

• dichloromethane or tetrahydrofuran, the reaction of disubstituted ketenes and N-tosyl arylimines provided corresponding trans-β-lactams in moderate to excellent ee (up to 98%), diastereoselectivities (up to 99:1 dr), and yields (up to >99%). Of particular interest, this methodology facilitates the formation of

• diverse trans-β-lactams that are complimentary to the related cis-lactams. 2.10 [4 + 1] Annulations of MBH carbonates with dienes Phosphine-catalyzed asymmetric [4 + 1] annulations between MBH carbonates and activated dienes could be achieved when using the bifunctional phosphine G6 as the catalyst

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• eight benzyl protecting groups was accomplished using Pearlman’s catalyst under mild acidic conditions to give fumonisin B2 (20) [45][46][47][84]. Tricylic β-lactams (1997) β-Lactam antibiotics are the most prescribed and successful class of antibiotics developed and used in clinical practice. This