Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• wide range of substituents on (hetero)aryl iodine(III) compounds, including electron-rich, electron-poor, sterically congested, and acid-labile groups, as well as a broad range of aliphatic and aromatic carboxylic acids for the synthesis of diverse aryl(TMP)iodonium(III) carboxylates in high yields

• reported [18][19] (Scheme 1). The importance of the trimethoxyphenyl (TMP) group as an auxiliary (dummy) ligand on the iodonium salt has prompted researchers to synthesize aryl(TMP)iodonium(III) trifluoroacetates via oxidation of iodoarene with m-chloroperbenzoic acid (mCPBA) in the presence of

• trifluoroacetic acid, followed by coupling with 1,3,5-trimethoxybenzene [18] (Scheme 1A). This process demonstrated tolerance for a wide range of electron-rich and electron-deficient (hetero)aryl iodine(III) compounds. Wirth and colleagues reported the flow synthesis of diaryliodonium(III) trifluoroacetates using

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• been five natural MMFs isolated and characterized, with all of the MMFs being isolated from Streptomyces coelicolor W75 (Figure 1B). These compounds are 2,3,4-trisubstituted furans, and all five contain a carboxylic acid at the three position and a hydroxymethyl group at the four position. They differ

• the probe was synthesized in good yields, the optimization of the Diels–Alder reaction was undertaken. The Diels–Alder reaction (Figure 3A) was optimized utilizing 3-furoic acid (14) as it fits the requirement of having an electron-withdrawing group in the three position and was an inexpensive

• the carboxylic acid in the three position, the phenyl group is most likely too electron-donating, as well as potentially being too sterically bulky. Finally, pyrrole 21 was tested and ultimately resulted in an inconclusive amount of conversion. Compound 21 does not ionize well on our LC–MS and thus we

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• 1883 and involves its synthesis from phenylhydrazine and an aldehyde or ketone using an appropriate acid catalyst [8]. In the following years, new processes were developed for the synthesis of indole such as the Castro, Bischler, and Larock synthesis etc. [2][9][10]. Carbonylation reactions represent a

• 2018, 2022 and 2023, developed three procedures for the synthesis of substituted indoles from functionalized nitro compounds by using, in the first two cases phenyl formate as CO source [39][40] and, in the third case formic acid [41]. All of three processes allow the use of inexpensive reactors, in

• 2022, some substrates led to a non-selective reaction (Scheme 20). On the other hand, in the approach in which formic acid was used, the catalyst system was Pd(acac)2/1,10-phen. Also, in this case the addition of Et3N favored the reaction, moreover, Ac2O was added as additive (Scheme 21). At the same

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• depyrophosphorylation, whereas class II TSs utilize a general acid (a key Asp residue) to protonate the terminal C=C bond or epoxide group to yield a tertiary carbocation. The highly reactive carbocation is then converted to different carbocation intermediates, facilitated by the hydrophobic pocket of the TSs, which

• , that bind trinuclear magnesium clusters for diphosphate abstraction, whereas class II TSs have a DXDD motif that acts as the catalytic acid. Recently, several novel unconventional TSs that share low sequence and structural similarities with classical TSs have been discovered and comprehensively

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• Institute, Palackӯ University in Olomouc, Olomouc, Czech Republic 10.3762/bjoc.20.85 Abstract Tetrazole is widely utilized as a bioisostere for carboxylic acid in the field of medicinal chemistry and drug development, enhancing the drug-like characteristics of various molecules. Typically, tetrazoles are

• ready-to-screen drug-like molecules remains a key challenge in the medicinal chemistry field [5][6]. Tetrazole is considered as a privileged scaffold in pharmaceutical and medicinal chemistry, used as a carboxylic acid bioisostere and a cis-amide mimic contributing to improvements in lipophilicity

• (Figure S1, Supporting Information File 1). Thus, we examined the ability of the Passerini reaction to incorporate an oxo-tetrazole group with a diverse panel of isocyanide and acid derivatives. Various aliphatic and aromatic acid derivatives are well tolerated leading to the corresponding tetrazole

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• studied due to the easy accessibility of fluoride ions with many methods directly employing the parent carboxylic acid as substrate. These processes avoid an additional pre-functionalisation step and have been reported using a range of deoxyfluorinating reagents including (diethylamino)sulfur trifluoride

• -handle solids that can be readily produced on a multigram scale from relatively inexpensive starting materials. During the optimisation studies for the latter process with carboxylic acid substrates, in addition to the desired (trifluoromethyl)thioester products, small amounts of the corresponding acyl

• to deliver acyl fluorides via two distinct deoxyfluorination pathways, an efficient process could be achieved using only sub-stoichiometric amounts of the fluorinating reagent. Results and Discussion In an initial test reaction, 4-methylbenzoic acid (1a) was reacted with 1.25 equiv of BT-SCF3 and 2.0

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• schistosomiasis [22][23][24][25]. The combination of the privileged heterocycles tetrazole and tetrahydroisoquinoline in one molecule generates new molecules which could have biological activities. A standard Ugi four-component reaction (Ugi-4CR) of an aldehyde, amine, isocyanide, and a carboxylic acid produces

• highly diverse peptidic structures A with up to four points of substitution (Scheme 1) [26][27]. By replacing the carboxylic acid with a nucleophilic azide reagent XN3 (generally TMSN3), the Ugi-azide four-component reaction (UA-4CR) of an aldehyde, amine, isocyanide, and azide gives 1,5-disubstituted 1H

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• low yield of the first approach. Replacing the catalyst and increasing the temperature or the amount of boronic acid proved to be unsuccessful. With entry 6 (Table 1) it was shown that similar yields could be obtained by removing the ligand and using higher amounts of catalyst. Therefore, no

• (5k, 5l, 5r). However, this effect seems to be neutralized when using an electron-rich arylboronic acid (5m). Lower yields are obtained when an acceptor group is present on the arylalkyne (5p, 5q). This leads to the suggestion that an electron-donor group activates and an electron-withdrawing group

• glacial acetic acid (60 mL) and after 5 min acetic anhydride (3 mL) was added. The reaction mixture was stirred for 10 min. Then, bromine (1 equiv; 23.4 mmol; 1.2 mL) was slowly added dropwise. After 1 hour, the reaction was stopped by adding water (25 mL) and cooling to 4 °C for 30 minutes. The

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• activity, if not an improvement [1]. Often-used bioisosteres include the tetrazole group for a carboxylic acid [2][3][4][5] and fluorine atoms in place of hydrogens [6][7]. The inclusion of fluorine can alter the polarity of a molecule and can also be used to prevent epimerisation, as seen in

• esterification of alcohol (±)-5 gave redox active ester (±)-6, which was itself shown to be a suitable substrate for nickel-catalysed decarboxylative cross coupling reactions to aryl-substituted BCPs (±)-7. Oxidation of alcohol (±)-8 gave acid (±)-9 which yielded amine (±)-10 after a Curtius rearrangement

• -workers also reported the modification of these 1,2-BCHs to increase the number of derivatives accessible using this approach (Scheme 3B) [38]. Transformation of the naphthyl ketone moiety of BCH (±)-25d by Baeyer–Villiger oxidation followed by hydrolysis gave carboxylic acid (±)-26. Through Curtius

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• originated from two key C5 building blocks, namely isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are biosynthesized via either the methylerythritol phosphate (MEP) pathway or the mevalonic acid (MVA) pathway by using the primary metabolites. Different numbers of IPP and DMAPP

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• acid, trifluoroborate moiety, trifluoromethanesulfonate, aryl sulfonamides, and heterocycles, have been incorporated into the ortho-position of diaryliodonium structures [16][17][18][19][20][21]. Ortho-trimethylsilyl or boronic acid-substituted diaryliodonium salts can serve as aryne precursors. Ortho

• solvents including dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), toluene, acetic acid (AcOH) and water (Table 1, entries 9–13) were carried out. However, polar solvents such as AcOH and H2O were proved to be unsuitable for this reaction. For catalysts, we found that Cu(OAc)2 gave the best results

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• physiological function of NNG are discussed below. Results Screening of Vs NnlA homologs for NNG degradation activity To select Vs NnlA homologs to test for NNG degradation activity, we performed a BLAST search of the Vs NnlA amino acid sequence in the NCBI database. This search resulted in retrieval of 99

• homologous amino acid sequences with an E-value of less than 1 × 10−10. A subset of 55 of these sequences was selected with a query cover of greater than 88%. From these sequences, we selected five homologs of the nnlA gene [Pseudovibrio denitrificans JCM 1230 (Pd), Pseudovibrio japonicus strain KCTC 12861

• (Pj), Pseudonocardia spinosispora DSM 44797 (Ps), Mycobacterium sp. 1465703.0 (Ms), Microbispora rosea subsp. nonnitritogenes strain NRRL B-2631 (Mr)], which were synthesized and cloned into E. coli recombinant expression vectors. These homologs ranged in amino acid sequence identity from 46 to 76

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• sulfites were not intermediates in the reaction manifold. Furthermore, the isolation of some starting alcohols in the reactions of 10b and 10d following chromatography was attributed to hydrolysis of the corresponding dialkyl sulfite 13b and 13d on silica, a process that can be acid or base-catalysed [26

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• significant in industrial applications, renowned for its production of diverse natural products with chemical structures and bioactivities, such as cephamycin C, clavulanic acid, and isopenicillin N [22][23][24]. Genomic sequencing of S. clavuligerus has revealed 48 potential secondary metabolite BGCs, and

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• involving the in situ-formation of HCl gas. Lastly, the third section discusses reactions using an aqueous solution of HCl (hydrochloric acid). It is crucial to emphasize the distinction between hydrochloric acid and HCl (gas) or HCl solutions in apolar solvents, as HCl molecules in hydrochloric acid are

• , 3.0 M in methanol, 3.0 M in 1-butanol, 2.0 M in diethyl ether, 3.0 M in cylopentyl methyl ether, 1.0 M in acetic acid. Terminal aliphatic alkenes, such as prop-1-ene (7) do not react with HCl gas at rt and pressures of 1 atm or less (Figure 3A) [37]. In contrast, higher pressures and temperatures

• by bubbling HCl gas, generated from NaCl and H2SO4, into dry DMPU. This yields a 14 M solution of HCl in DMPU, a concentration significantly higher than HCl solutions in other organic solvents. Further enhancement of the reaction was achieved through the addition of acetic acid. The reaction displays

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• of hydrophilic oligopeptide anchors (oligo-Lys, oligo-Glu, and oligo-Arg) were synthesized. A previously reported Prato reaction adduct of a biscarboxylic acid-substituted C60 derivative was subjected to a solid phase synthesis for amide formation with N-terminal amines of peptides on resin to

• inhibition [34]. For the covalent functionalization, we have previously developed a versatile and convenient biscarboxylic acid-substituted C60 derivative (3, Figure 1) [35], which was prepared via the Prato reaction [36]. We used this derivative 3 as a starting material and synthesized a series of water

• C60–peptide conjugates in this study. In addition to the water solubility introduced by the peptides, these conjugates have a superior biocompatibility compared to those with synthetic polymers, such as PEG and PVP. We utilized the previously reported biscarboxylic acid derivative 3, which was

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• the ability of the amino group in porphyrin 5 to enter acylation reactions with 4-(N-maleimido)benzoyl chloride (8, prepared in situ from 4-(N-maleimido)benzoic acid (9) and oxalyl chloride) and chloroacetyl chloride (10) with the aim of using these compounds for further functionalization. The

• known to enhance the aqueous solubility and tumor selectivity of hydrophobic drugs through the enhanced permeability and retention effect [46]. It was also shown that porphyrin 6 undergoes reaction with taurine (2-aminoethanesulfonic acid, 25) which is an essential nutraceutical with diverse

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• culture conditions. Du et al. identified a new compound (designated ishigamide (10)) as 3-([2E,4E,6E,8E]-13-hydroxytetradeca-2,4,6,8-tetraenamido)propanoic acid and elucidated the biosynthetic machinery (Figure 2c) [43][44][45]. Seo et al. synthesized ishigamide and determined its absolute configuration

• orsellinic acid, lecanoric acid, and the compounds F-9775A and F-9775B. Lee et al. discovered that secondary metabolism in Streptomyces coelicolor A3(2) M145 is activated by iron competition during co-culture with Myxococcus xanthus [110]. Co-culture promotes the production of the siderophore myxochelin in M

• Streptomyces and mycolic acid-containing bacteria (MACB) activates secondary metabolism [111]. In their method, direct attachment by live MACB cells is thought to alter secondary metabolism in the Streptomyces cells [112]. Using this method, Onaka et al. identified a variety of new compounds, such as

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• family are the monoglycosyl, diglycosyl, or triglycosyl products of 8,8′-diapocarotene-8,8′-dioic acid (crocetin, 1) or derivatives thereof. In addition to C. sativus and G. jasminoides, Buddleja officinalis and Buddleja davidii from the Loganiaceae family [1][2], Nyctanthes arbor-tristis from the

• and enhance the antiepileptic effect of diazepam. The mechanism of action involved γ-aminobutyric acid (GABA) [38][39][40]. The brain-derived neurotrophic factor (BDNF)–tropomyosin receptor kinase B (TrkB) pathway is closely associated with epilepsy. Crocin can increase the BDNF level in the cortex of

• showed that the strain expressing NcALD8 could produce 4.42 mg/L of crocetin (1) [109]. In addition to the de novo biosynthesis of crocetin (1), Shan et al. reported the biotransformation of crocetin (1) from zeaxanthin (7). When the 3-OH-β-apo-8'-carotenoic acid (3-HACA) byproduct was eliminated by

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• only for the incorporation of one extender unit [2][3]. Although enzyme domains with various specialised catalytic functions can be found as integral part of polyketide synthases, three domain types are fundamental to their biosynthesis, resembling the same logic as observed for fatty acid biosynthesis

• understanding of polyketide biosynthesis has been reached, including a detailed knowledge of the extender unit selection and the stereochemical implications that are predictable from amino acid sequences [5][6]. The polyene antibiotic bacillaene was first isolated from Bacillus subtilis [7]. This soil-dwelling

• by the preceding modules (highlighted in purple) [14][16]. Furthermore, the structures of 1 and 2 show a shifted triene portion that is not in conjugation with the carboxylic acid function. NMR studies of off-loaded intermediates with the TE deletion mutant revealed that these double bond shifts are

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

• several positions and also form 6–14 residue cyclic peptides [37][38]. It should be noted that TycC TE was more sensitive to the amino acid changes near the site of ring closure. The alkyne-containing analogs were conjugated to a variety of azido sugars via copper(I)-catalyzed cycloaddition to obtain the

• cyclization process. Most recently, the synthesis of monocyclic depsipeptide, seongsanamide E (10), was reported by Boddy and co-workers via two different strategies [43]. On the one hand, the regular chemical approach, attempting Yonemitsu’s conditions to macrolactonize the seco-acid, was unsuccessful. On

• developed to address this challenge to produce daptomycin and its derivatives. These approaches include biosynthetic [49], chemoenzymatic [50], solid-phase [51], and solution-phase methods [52], but most only encompass modifications of the lipid chain and specific amino acid mutations. Learning from the

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• gene (AsGGS), suggesting that they are related to the biosynthesis of diterpenes (Figure 2A). AsPS and AsCPS consist of αβ and αβγ domains, respectively. Further sequence analysis revealed that the β domain of AsPS contains a mutation at the catalytic aspartic acid residue, indicating that this enzyme

• GGPP, followed by hydrolysis by acid phosphatase. GC–MS analysis revealed that AsCPS synthesizes the same product to ObCPS_11g (see Supporting Information File 1, Figure S4A and B). It should be noted that the stereochemistry of CPP needs further verification due to the lack of chiral resolution of our

• ObCPS_11g are shown. B) Proposed reactions catalyzed by AsPS, AsCPS, and acid phosphatase. Characterization of CiCPS-PS. A) GC–MS analysis of the transformant expressing CiCPS-PS and AsGGS. EICs at m/z 272 are shown. The peak marked by the asterisk is probably derived from the host strain. B) Putative

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• , suppressed the reaction by reducing Ph­EBX (2) (Table 1, entry 6). Using diisopropyl ether as a milder donor had no effect on the reaction (Table 1, entry 7). Next, we tested reducing agents expected to react with the iodanyl radical. The addition of ʟ-ascorbic acid led to no improvement of yield and

• acid B(OTFE)3 had a detrimental effect (Table 7, entry 7). Increasing the stoichiometry of BF3 to 2 equivalents lowered the yield significantly (Table 7, entry 8). In contrast, the loading could be reduced to 30 mol % without impacting the formation of 4a (Table 7, entries 9 and 10). Finally, a fine

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• serve as a nutrient source for phytoplankton and other organisms [4]. The distinctive structural feature of these siderophores is the α-hydroxy carboxylic acid (i.e., β-hydroxyaspartate), relevant to a photoreactive functional group [2][4]. In 2016, using the gene encoding a hydroxylase specific to the

• serine (Ser), a β-hydroxyaspartic acid (Hya), and a unique γ-amino acid biosynthetically originating from an arginine and a methyl malonate (4-amino-7-guanidino-3-hydroxy-2-methylheptanoic acid), with the amino group acylated by a saturated fatty acid. Subsequent HMBC and MS/MS analyses indicated that

• -guanidino-3-hydroxy-2-methylheptanoate, indicating that the N-terminal fatty acyl group is a tetradecanoic acid in 2 (Figure 1 and Figure S10 in Supporting Information File 1). Therefore, compound 2 is concluded to be the known lipohexapeptide variochelin B [5]. Compound 3 has the chemical formula of

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• -light-mediated palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines, affording unsaturated γ- and ε-amino acid derivatives with diverse structures. In this methodology, the diazo compound readily transforms into a hybrid α-ester

• -amino acid derivative. This approach proceeds under mild and simple reaction conditions and shows high functional group tolerance, especially in the incorporation of various bioactive molecules. The studies on scale-up reactions and diverse derivatizations highlight the practical utility of this

• owing to their wide applications in medicinal chemistry [1][2][3][4][5]. γ- and ε-AA derivatives are widely distributed in peptide natural products, bioactive molecules, and drugs, such as pregabalin, baclofen, ε-aminocaproic acid and lysine (Scheme 1a) [6][7][8][9][10][11][12]. The number of reported