Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• impurity generated in this process. Nucleophilic acyl substitution competes with aromatic substitution to displace glutarimide and gives a byproduct that can co-elute with the desired product on HPLC throughout the remainder of the synthesis. Scavenging with taurine is a convenient way to minimize this

• contamination. Keywords: glutarimide; IMiD; impurity; nucleophilic acyl substitution; PROTAC; Introduction Targeted protein degradation capitalizing on the concept of chemically induced dimerization has emerged as a new therapeutic approach recently [1]. In particular, the modularity of proteolysis targeting

• of 5 using the same sequence of reactions starting from 3-fluorophthalic anhydride instead of 1. Indeed, 5 is a white solid without UV absorption around 410 nm (Figure 2). The formation of 6 originated from nucleophilic acyl substitution to displace the glutarimide in 1 by 2. Interestingly, this side

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• component into a glutarimide framework employing a Rh2(esp)2-catalyzed N–H insertion with the involvement of N-Boc-α-diazo glutarimide. The new diazo reagent is more stable, soluble and convenient to prepare than the previously suggested one. The approach permits the application of diverse heterocycles

• strategies is cereblon (CRBN), the target focus of a collection of immunomodulatory drugs containing the glutarimide moiety such as thalidomide, pomalidomide, lenalidomide [12][13], and avadomide [14] (Figure 1). These ligands, although prevalent recruiters in PROTAC design, present several drawbacks

• including the degradation of lymphoid transcription factors [15][16][17] IKZF1, IKZF3, and SALL4 where the latter's degradation could result in a significant teratogenic effect [18]. In addition, these glutarimide derivatives are highly susceptible to hydrolysis and enzymatic cleavage under physiological

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• ]. Compound 1 is a benzofuranone, structurally related to enalin A and pseudopithonone, isolated from the fungus Verruculina enalia and the marine-derived fungus Pseudopithomyces maydicus, respectively [12][29]. Its core structure is also like actiketal, a new member of the glutarimide antibiotics, previously

• isolated from Streptomyces [30] and whose antimicrobial activity is probably related to the glutarimide moiety. In compound 1, the lack of this moiety, in addition to the fact that it has been isolated as a racemate could not lead to any beneficial property. As for compound 2, it is a diacetylated

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• cyclization reaction of succinimide and glutarimide-derived hydroxylactams 7 (Scheme 3) [33]. This system was designed in a way that key experimental observations could be made to analyze whether a SN1 or SN2-type mechanism takes place. A strong dependence of the enantioselectivity on the counterion and

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

• irreversible one-electron oxidation at 0.80 V, in accordance with the involvement of oxygen in the reaction. Remarkably, when the glutarimide was labeled with deuterium in position 3, the deuterium labeling was transferred to the hydrocarbon liberated in the reaction, showing that hydrogen abstraction was

Diastereoselective Mannich reactions of pseudo-C₂-symmetric glutarimide with activated imines

• Tatsuya Ishikawa,
• Tomoko Kawasaki-Takasuka,
• Toshio Kubota and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 2473–2477, doi:10.3762/bjoc.13.244

• article. Results and Discussion On the basis of our previous study [4], the chiral glutarimide 1a was employed as the starting material and optimization of reaction conditions with benzaldehyde-based imines 2 was performed (Table 1). Lithium enolate by the action of LDA to 1a was found to be ineffective

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• important to the activities of cycloheximide congeners. Keywords: antifungal activity; cycloheximide derivatives; E/Z photoisomerization; Streptomyces sp; theoretical conformational analysis; Introduction The glutarimide-containing antibiotics represent a fascinating class of natural products that exhibit

• used. Solvent effects were treated using PCM. To build 3D conformers of 2a and 3a, the global energy minima of 2 and 3, obtained in above ECD computations, were used and their glutarimide ring was replaced by a hydrogen atom. The built conformers were subjected to geometry optimizations to obtain the

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• isoprenoid biosynthesis. The designated branching modules of lactone and glutarimide-producing PKS show similar designs: a branching domain (B or X), which is flanked by a KS and an ACP domain (Scheme 20b and c). In vitro reconstitution experiments with the branching module of the macrolide rhizoxin (130

• as well as amino and carboxamide nucleophiles in lieu of a hydroxy group in 132 were accepted, yielding δ-lactam and glutarimide moieties, respectively [131][132]. When the B-domain of the rhiPKS was exchanged with an X-domain of glutarimide-producing PKS from the 9-methylstreptimidone PKS of S

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• of (R)-3-(tert-butyldimethylsilyloxy)glutarimide 14. After O-desilylation and Dess–Martin oxidation, the resulting keto-lactam 10 was subjected to a highly trans-stereoselective addition of the methylmagnesium iodide to give carbinol 11 as sole diastereomer. An efficient ring closure procedure

• ][31], among them L-proline and its derivative were used as popular precursors from the pool of chiral compounds [13][14][15][18][19][20][21][22]. Herein, we report a concise diastereoselective synthesis of (8S,8aS)-5 starting from (R)-3-(tert-butyldimethylsilyloxy)glutarimide 14, a versatile building

• recovered starting material 16. Due to the low yield in the debenzylation process, we decided to change the O-protecting group from benzyl to TBDMS, namely, use of TBDMS ether 14 as the starting material. Thus, (R)-3-(tert-butyldimethylsilyloxy)glutarimide 14 [49] was prepared from the known (R)-3

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• (PDE4) inhibitor apremilast (11), which lacks the glutarimide is currently in phase III clinical trials. The first naturally occurring isoindole, 6-methoxy-2,5-dimethyl-2H-isoindole-4,7-dione (18), was isolated from the sponge Reniera sp. in 1982 [10]. The postulated structure was elucidated through

Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• (Scheme 5). Grignard addition to the glutarimide Mg-salt 20 followed by reduction of the Mg salt 21 afforded lactam 22 as an inseparable 1:1 mixture of two diastereomers in 77% overall yield [68][69][70]. Vinylogous amide 23 was prepared by O-methylation of lactam 22 with freshly distilled MeOTf followed

Synthesis of (−)-julocrotine and a diversity oriented Ugi-approach to analogues and probes

• Ricardo A. W. Neves Filho,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2011, 7, 1504–1507, doi:10.3762/bjoc.7.175

• heterocyclic precursor as an amino input in Ugi four-component reactions (Ugi-4CR) [1]. Keywords: diversity oriented synthesis; julocrotine; leishmania; Mitsunobu reaction; Ugi reaction; Introduction Julocrotine (1) is a natural glutarimide alkaloid isolated from several plants of the genus Croton [2][3][4

• ], including Croton cuneatus Klotzsch, which is used by Amazonia natives in anti-inflammatory and analgesic medicines. The structure of this glutarimide-containing alkaloid was first proposed in 1960, based upon a series of degradative experiments, but only confirmed in 2008 by X-ray analysis [5][6][7]. Most

• ]. In addition, the glutarimide motif can be considered as a privileged structure. Compounds with this pharmacophore often exhibit a wide range of biological properties including anti-inflammatory [10], antitumor [11][12], and anticonvulsive properties [13]. Because of the low yields of julocrotine

A convenient allylsilane- N-acyliminium route toward indolizidine and quinolizidine alkaloids

• Roland Remuson

Beilstein J. Org. Chem. 2007, 3, No. 32, doi:10.1186/1860-5397-3-32

• hydroxyalkylallylsilane 32 is accomplished in 40% yield following Trost's procedure. [48] Reaction of glutarimide with alcohol 32 under Mitsunobu reaction conditions afforded imide 33 in 67% yield. Reduction of 33 was carried out with an excess of sodium borohydride in methanol at 0°C to give 34 as a mixture of two

• trimethylsilylmethylmagnesium chloride addition to ethyl (S)-3-hydroxybutanoate as we described. [50] The first three steps of the enantioselective synthesis were those previously described for the synthesis of racemic compounds (vide supra). Condensation of alcohol 32 with glutarimide under Mitsunobu conditions led to

• glutarimide under Mitsunobu conditions led to imide 40 in 46% yield. Reduction of 40 with diisobutylaluminium hydride afforded hydroxylactam 41 isolated as a mixture of isomers, a higher yield of a single isomer was obtained when using lithium triethylborohydride as reducing regent. The reduction had to be