New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• . Compound 4a was then allowed to react with triphenylphosphine in CH2Cl2 at room temperature for 2 h to produce the iminophosphorane 5a by Staudinger reaction. Aza-Wittig reaction of 5a with phenyl isocyanate generated carbodiimide 6a, which was then treated with diethylamine to form the guanidine

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• guanidine to a carbodiimide was reported by Richter and Ulrich in 1981 (Scheme 38) [78]. The authors prepared an N1,N2,N3,N4,N5-pentaarylbiguanide derivative by reacting an N,N’,N’’-triarylguanidine with diphenylcarbodiimide. The reaction occurred at room temperature in dichloromethane with a high yield

• equivalents of the carbodiimide in the reaction with N,N’-disubstituted guanidines resulted in the formation of 1,2-dihydro-1,3,5-triazine derivatives as the main products of the cycloaddition reaction [82]. They also showed that increasing the amount of the carbodiimide to 3 equivalents led to excellent

• guanidine as a side-product was explained by the reaction between the newly formed amine and the excess of carbodiimide. Biguanide-like compounds: Besides the formation of orthodox biguanides, a number of examples for reactions between guanidine-like compounds and carbodiimides have been described. For

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• ]quinoline framework via electrocyclization of 2-(pyrrol-3-yl)benzene containing a carbodiimide moiety as a 2-azahexatriene system. The employed six-step sequence afforded trigonoine B (1) in 9.2% overall yield. The described route could be employed for the preparation of various N-substituted 4

• -aminopyrroloquinolines with various biological activities. Keywords: 2-azahexatiriene system; carbodiimide; electrocyclization; pyrrolo[2,3-c]quinoline; trigonoine B; Introduction In 2011, two novel alkaloids, namely trigonoine A and B, were isolated from the leaves of Trigonostemon lii by Hao and co-workers [1]. The

• by electrocyclization of 2-(pyrrol-3-yl)benzene containing a carbodiimide moiety as a 2-azahexatriene system. Results and Discussion Scheme 2 illustrates the retrosynthetic strategy designed to synthesize triogonoine B (1). It was speculated that the dihydroquinoline moiety of trigonoine B (1) could

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• given in Scheme 9 [87]. On this pathway for the synthesis of conjugates 19 and 20, acid 18 is cross-linked with a peptide component using a milder carbodiimide method via the starting methanofullerene 17. Similar to Scheme 8, fullerene adducts 21 and 22 with glycine and phenylalanine, respectively, were

• heating, or photochemically in a nitrogen atmosphere (Scheme 23) [109]. The reaction of spiro[10-anthron-9,61'-methanofullerene] (79) [110] with bis(trimethylsilyl)carbodiimide and malononitrile in pyridine in the presence of TiCl4 resulted in spirocyclic blocks 80 and 81, respectively (Scheme 24) [111

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• ), we found that the yield of BTA 3a depended on the method of the addition of the reagents (Table 1, procedure A or B). In case of some non-polar solvents (toluene, 1,4-dioxane), the addition of o-aminothiophenol (1a) before the carbodiimide resulted in higher yields of BTA 3a, and in case of some

• polar solvents (acetonitrile, ethyl acetate, DMF, and N-methyl-2-pyrrolidone), addition of the carbodiimide before o-aminothiophenol (1a) afforded higher yields of BTA 3a. Noteworthy, the solvents strongly influenced the studied reaction. When DMSO was used as a solvent (Table 1, entries 5 and 6), only

• trace amounts of the target compound 3a were formed, probably, because the combination of DMSO and a carbodiimide induced multiple side-processes similar to the Pfitzner–Moffatt oxidation [29]. In case of hexane as a solvent (Table 1, entries 19 and 20), only traces of compounds 3a and 4a were observed

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• with (R)-3-(2-naphthylmethoxy)tetradecanoic acid (7) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 4-dimethylaminopyridine (DMAP) as the activation reagents [14] to give the key/common building block 15 in good yield (Scheme 2). Glycosyl acceptor 18 and donor 20 were thus conveniently

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• coupling reagents, such as benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) or diisopropyl carbodiimide (DIC) and additives, such as 1-hydroxybenzotriazole (HOBt) or triethylphosphine. [29][30][31] However, in our hands, none of the described methods reached the high yields that

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• structures (c) can also be formed by treating the C30 carboxyl group with piperazine in the presence of activators (e.g., 1-ethyl-3-(dimethylaminopropyl)carbodiimide hydrochloride (EDCl), 1-hydroxybenzotriazole (HOBt) and trimethylamine [18]), the yield of piperazinyl amide derivatives was 80.6% [19]. These

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

• -ᴅ-Ala (16) was coupled to O-benzylserine ethyl ester 37 to give dipeptide 38, hydrogenolytic debenzylation gave the substrate 39 for the copper(I)-mediated elimination of the carbodiimide formed in situ using EDC, and then yielded the dipeptide Boc-ᴅ-Ala-Dha ester 40 in good yields. Lithium

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• racemic Boc-protected (adamant-1-yl)glycine [32] 2 using the carbodiimide EDC/HOBt method [21]. The obtained mixture of BocAdGly-ʟ-Ala-ᴅ-isoGlnOBn diastereoisomers was treated with trifluoroacetic acid in order to remove the Boc protecting group while the diastereoisomer 4 with ᴅ-ʟ-ᴅ amino acid sequence

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• bond formation was achieved using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl), 1-hydroxybenzotriazole (HOBt) and N,N-diisopropylethylamine (DIPEA) in DMF under microwave irradiation (Scheme 1). Racemic 1 was synthesized using tryptamine and (rac)-3-methyl-2-oxopentanoic acid

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• -16OH-C16:1-NAME with [M + H − H2O]+ 356, b) Z9-C16:1-NABME (8) with [M + H]+ 354, c) Z9-C16:1-NAVME (9) with [M + H]+ 368, and d) Z9-C16:1-NAGME (11) with [M + H]+ 326. Synthesis of iso-C15:0-NAME (6). DMAP: 4-dimethylaminopyridine, EDC: 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, L

Functionalization of graphene: does the organic chemistry matter?

• Artur Kasprzak,
• Agnieszka Zuchowska and
• Magdalena Poplawska

Beilstein J. Org. Chem. 2018, 14, 2018–2026, doi:10.3762/bjoc.14.177

• carbodiimide-promoted reactions [13][14]. As presented in Figure 2, step a, the first step of a carbodiimide-type conjugation involves the generation of an O-acylisourea intermediate, which is highly electrophilic and which bears the urea-based good leaving group. Such activation of carboxyl groups onto a

• for ester bond formation [15]. 4-(N,N-Dimethylamino)pyridine (DMAP) is as an additive in the carbodiimide-coupling protocol. In the second step, DMAP forms active amide intermediates via a reaction with an O-acylisourea individual (Figure 3). This is because DMAP is a stronger nucleophile than the

• mediated by the 1,1’-carbonyldiimidazole, which acts as the coupling reagent. The mechanism of this method is presented in Figure 6. The basic principles of this process are the same as for those of carbodiimide-mediated protocol (a reaction between activated ester and a nucleophile). As presented in

A self-assembled photoresponsive gel consisting of chiral nanofibers

• Lei Zou,
• Dan Han,
• Zhiyi Yuan,
• Dongdong Chang and
• Xiang Ma

Beilstein J. Org. Chem. 2018, 14, 1994–2001, doi:10.3762/bjoc.14.174

• -dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 8.04 g, 0.044 mol) and 1-hydroxybenzotriazole (HOBt, 5.94 g,0.044 mol) were added to a 200 mL CH2Cl2 solution of Boc-L-glutamic acid (5 g, 0.02 mol) and 4-aminoazobenzene (7.8838 g, 0.04 mol), then the obtained mixture was stirred at room temperature for 72 h

Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae

• Bimal Koirala,
• Robert A. Hillman,
• Erin K. Tiwold,
• Michael A. Bertucci and
• Yftah Tal-Gan

Beilstein J. Org. Chem. 2018, 14, 1769–1777, doi:10.3762/bjoc.14.151

• ) procedures [34]. Phenylglycine and norvaline derivatives were prepared on a CEM Discover microwave synthesizer, with diisopropyl carbodiimide (DIC) as the coupling reagent along with Oxyma Pure. The ratio of DIC:Oxyma Pure:AA was 3.6:3:3 dissolved in N,N-dimethylformamide (DMF) for a final DIC concentration

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• was then converted into a reactive carbodiimide 24 and coupled to a terminal amino group of the solid phase 25 (Scheme 2). This coupling furnished solid phase-attached intermediate 26, which was Fmoc-deprotected to the amine 27. Iterative repetition of this coupling-deprotection cycle gave oligomer 28

• monomer 30 to the corresponding carbodiimide 31 (Scheme 3). Using long-chain alkylamine controlled pore glass (CPG) loaded with 5′-amino-5′-deoxythymidine (32) as solid phase, the reaction cycle started with the guanidine-forming coupling of 31 and 32 to give 33, followed by acidic cleavage of the MMTr

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• amines in the presence of a coupling reagent is the most convenient and simplest way [1][2][3][4][5][6]. The most commonly used coupling reagents such as carbodiimide [7], phosphonium [8], and uronium salts [9] are efficient and commercially available. In spite of these merits of traditional coupling

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• assay is another approach to avoid stalling due to inhibition. As mentioned in the Introduction, ligation reactions had been achieved by Naylor and Gilham in aqueous media in presence of a water-soluble carbodiimide as condensing reagent [7]. Likewise, Sulston et al. had used EDC to oligomerize AMP in

• equilibrium for the incoming nucleotide to the bound side, and thus strengthen the template effect. The proposed mechanism for the reaction is shown in Figure 15. In order to start the activation, the carbodiimide has to react with the phosphate group, leading to what is sometimes called a "covalent adduct

• above occur spontaneously in cold aqueous solution, without the need for mineral surfaces or enzymes. Condensation producing peptido nucleotides also occurs with other activating agents, such as cyanamide or carbonyl diimidazole (CDI). Cyanamide, a tautomer of unsubstituted carbodiimide, has long been

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• presence of methanolic sodium hydroxide to give corresponding carboxylic acids 134. Aminobenzothiazoles 135 were linked with carboxylic acids 134 to provide the amide derivatives (benzothiazolyl derivatives, 136) using amide coupling reagent 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• ]-L-proline methyl ester (5): N-Phtaloylglycine (4 mmol), 1-hydroxybenzotriazole (4.4 mmol) and N-ethyl-N’(3-dimethylaminopropyl)carbodiimide hydrochloride (10 mmol) were placed in a microwave vial. To the microwave vial was added anhydrous DMF (8 mL) and anhydrous N,N-diisopropylethylamine (20 mmol

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• -3-(3-dimethylaminopropyl)carbodiimide (EDC), ethyl cyano(hydroxyimino)acetate (oxyma) in the presence of a base and a liquid additive, were adapted to the preparation of Z–Pro–Pro–OMe (7) and Boc–Pro–Pro–OMe (8, Table 1). It consisted in ball milling the two amino acid derivatives 5 or 6 with 2 in

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• time to 4 hours and increasing the catalyst loading to 10–20 mol %. In general, there was no reactivity without CuCl, in solution or in the presence of a base instead of CuCl, implying that CuCl activated the carbodiimide component during this catalytic reaction. Tan and Friščić further developed this

• mechanochemical synthetic strategy and applied it to a previously unknown carbodiimide insertion into sulfonimides, resulting in two-atom ring expansion and chain extension reactions [51]. Saccharin was selected as a model cyclic sulfonimide substrate, while 4-methyl-N-tosylbenzamide was employed as an acyclic

• ., DCC (78%), N-ethyl-N'-tert-butylcarbodiimide (85%) and di-p-tolylcarbodiimide (80%, Scheme 21a). The performance of the reaction was not affected even on >1 g scale. Milling 4-methyl-N-tosylbenzamide (47) with DIC and CuCl (10 mol %) for 2 hours resulted in the insertion of the carbodiimide into the C

Interactions between shape-persistent macromolecules as probed by AFM

• Johanna Blass,
• Jessica Brunke,
• Franziska Emmerich,
• Cédric Przybylski,
• Vasil M. Garamus,
• Artem Feoktystov,
• Roland Bennewitz,
• Gerhard Wenz and
• Marcel Albrecht

Beilstein J. Org. Chem. 2017, 13, 938–951, doi:10.3762/bjoc.13.95

• -monoamino-6-deoxy-β-CD [52] using N,N’-dicyclohexyl-carbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt) applying a procedure known for terephthalic acid [53]. The resulting product, monomer 7, was easily isolated due to its low solubility in water which was attributed to self-inclusion between hydrophobic