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

• oxidation 201 were prepared from the corresponding cinnamic acids via condensation with ʟ-proline tert-butyl ester followed by ester hydrolysis. Upon oxidative dimerization under Ronlan’s electrochemical conditions, substrates 201 were converted to bislactones 202 with good enantioselectivity. The authors

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• class I TPSs. Interestingly, in CotB2, α-helix D is rather short as a proline residue, adjacent to the third aspartate of the aspartate-rich motif, introduces a kink. In the closed conformation D110 is directly involved in the coordination of Mg2+A and Mg2+C, whereas D111 forms a salt bridge with R294

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• amide (Scheme 19). With this method, both mono- and difluorinated benzoic acid derivatives can be selectively obtained in high yields. In 2014, Pu and co-workers [58] devised the regioselective Pd(PPh3)4-catalyzed electrophilic ortho-fluorination of 2-arylbenzothiazoles with NFSI and ʟ-proline as the

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

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• [18]. The synthesis of the retro-inverso analogue had been envisaged to prove that changing the amino acid configuration from ʟ to ᴅ and reversing of the peptide sequence should place the side chains in a similar manner as for the parent compound. Interestingly, replacing alanine by proline in AFGP

• analogues, which occasionally occurs in smaller natural AFGP (and furthermore proline is a precursor of the PP II helix) significantly decreased the inhibitory effect on the ice recrystallization of the compounds [19]. Here we present the synthesis of a series of model peptides comprising structural motifs

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• ) domain in the MicG homolog from Massilia sp. NR 4-1 revealed an aspartic acid residue at position 95 and a proline residue at position 144, which are both indicative for the formation of B-type alcohol stereochemistry [29]. The two motifs are also conserved in MicG and HMWP1 from micacocidin and

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• incorporate proline [15] and the furan functionality into pseudo-peptide catalysts. As shown in Scheme 2, Boc-L-proline and acetone were employed as acid and oxo components, respectively, in combination either with furfurylamine and cyclohexyl isocyanide or with (S)-α-methylbenzylamine and furfuryl isocyanide

• -peptide 1. Furfurylamine (177 µL, 2 mmol), acetone (116 mg, 2 mmol), Boc-L-Pro-OH (431 mg, 2 mmol) and cyclohexyl isocyanide (249 µL, 2 mmol) were reacted in MeOH (5 mL) according to the general procedure A. Flash column chromatography purification (EtOAc/hexane 1:1, v/v) afforded the Boc-proline-based

• ) were reacted in MeOH (5 mL) according to the general procedure A. Flash column chromatography purification (EtOAc/hexane 1:1, v/v) afforded the proline-based peptide 2 as colorless oil. Yield: 78%; Rf 0.30 (EtOAc/hexane 1:1, v/v); [α]D23 −6.26 (c 0.0047 g·cm−3, MeOH); 1H NMR (400 MHz, CDCl3) δ 1.40 (s

Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• -dependent methyl transferases were found forming a cluster together with the 2-MIB synthase in several Streptomyces species [26][27]. Besides the C-terminal domain typical of class I terpene synthases, these enzymes contain an additional proline-rich N-terminal domain that appears to be disordered in the

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• only viable alternative to bipyridine (Table 1, entry 7), with other ligands commonly used in copper-catalyzed reactions such as proline and 2,2,6,6-tetramethyl-3,5-heptanedione giving yields under 15%. Reducing the number of equivalents of boronic acid 25 and sodium carbonate was found to be well

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• of a catalytic amount of proline (Scheme 1) and then they were successfully converted to the appropriate esters 7 and acids 8. In our case, we have isolated products 4a–h individually and characterized them by IR, 1H, 13C NMR, and mass-spectral methods. The 1H NMR spectra of products 4 have two

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• as the promoter (not in a catalytic amount) of a Henry reaction and obtained the product with 99% ee. Subsequently, Doyagüez et al. [17] attached L-proline to β-CD via different linkers (including a triazole linker) and used the resulting organocatalysts in an aldol reaction in water, albeit with a

• lower enantiomeric excess (54% ee). Conversely, Shen et al. [18] performed an aldol reaction in a buffer using L- and D-proline-derived CDs connected through a pyrrolidine skeleton as catalysts and observed 94% ee. More recently, Liu et al. [19] reported the excellent enantioselectivity of 99% ee in an

• aldol reaction catalyzed by β-CD with L-proline attached through a urea moiety. Therefore, mainly proline-derived CDs have been previously tested as organocatalysts and mainly in aldol-type reactions. The limited number of functional groups attached to CD comprising mainly L-proline restricts the

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• chiral compounds were converted into the corresponding pyridin-4-ol derivatives and tested as chiral ligands in asymmetric catalysis [37]. Using the N-trityl-substituted proline as carboxylic acid provided the expected β-ketoenamide KE42 in low yield and as major product we isolated compound 7 in 49

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• (positive mode, NBA matrix) of cichorinotoxin over the mass range of m/z 150─1000. The segment identified based on the FABMS spectrum (peptide fragment b ions). NMR analyses of the segment consisting of 3-hydroxydecanoyl-dehydrothreonin-proline (600 MHz, acetone-d6). DhThr1 and Pro2 indicate that the first

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• pyroglutamic acids, proline and 4-hydroxyproline). Since various hydroxyglutamic acids were identified as components of complex natural products, syntheses of orthogonally protected derivatives of hydroxyglutamic acids are also covered. Keywords: amino acids; asymmetric synthesis; chiral catalysis; chiral

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• Anne Schnell J. Alexander Willms S. Nozinovic Marianne Engeser University of Bonn, Kekulé-Institute of Organic Chemistry and Biochemistry, Gerhard-Domagk-Str. 1, D-53121 Bonn, Germany 10.3762/bjoc.15.3 Abstract The mechanism of an L-proline-catalyzed pyridazine formation from acetone and aryl

• -substituted tetrazines via a Diels–Alder reaction with inverse electron demand has been studied with NMR and with electrospray ionization mass spectrometry. A catalytic cycle with three intermediates has been proposed. An enamine derived from L-proline and acetone acts as an electron-rich dienophile in a [4

• charge-tagged proline catalyst. The charge-tagging technique strongly increases the ESI response of the respective species and therefore enables to capture otherwise undetected reaction components. With the first two reaction variants, only small intensities of intermediates were found, but the temporal

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• hydrophobic cavity and chiral sites during a catalytic process [24][25]. Recently, we have reported a series of different functionalized organic catalysts based on calixarenes [26][34][35][36][37][38]. For example, we have been developed a calix[4]arene-based L-proline catalyst able to catalyze aldol

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• ones to the cationic charged residues, the purple circles to the polar uncharged residues and the green circle to a proline residue. The black line denotes hydrophilic and hydrophobic faces of the amphipathic structures. Red arrows show the mutation positions. MTT assays using Dec-NH2 and its synthetic

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• . reported the synthesis of a series of prolinamide and hydroxyprolinamide organocatalysts based on the calix[4]arene scaffold (Figure 8) [59]. Treatment of Boc-protected-L-proline or hydroxyproline with various aminocalix[4]arenes under one of the appropriate coupling conditions and subsequent deprotection

• good yields (up to >99%) with up to 97% ee and up to 85:15 dr (Scheme 20). In order to exploit the hydrophobic cavity of the calixarene platform in aldol reactions, two novel p-tert-butylcalix[4]arene-based chiral organocatalysts bearing L-proline units on the lower rim have been reported by Yilmaz et

• al. [60]. Coupling of calixarene diamine 60 with Boc-L-proline 74 or calixarene diacid chloride 76 with N-(2-aminoethyl)-N'-(tert-butoxycarbonyl)-L-prolinamide 77 and subsequent deprotection afforded catalysts 75 and 78 in good yields (Scheme 21). In 2014, an upper rim functionalized calix[4]arene

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• intramolecular cross-coupling of C−H bonds in 95 using catalytic chiral iodine 12 for the synthesis of a diverse array of spirooxindoles 96. Ishihara’s catalyst was modified by using an (S)-proline derivative to achieve a high level of enantioselectivity in the presence of peracetic acid (Scheme 21) [70]. They

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• depicted in Figure 2, PQS (4a) has an OH moiety that allows for its linkage to the organocatalyst proline 4b. Also, PQS has a lipophilic component that acts as a reaction solvent for hydrophobic dienes. The latter feature allows aldol reactions to take place efficiently in water. The aldol reaction between

• cyclohexanone and p-nitrobenzaldehyde was chosen to verify the performance of this nanoreactor. PQS-proline and the analogous mixed diester derivative of 4-hydroxyproline were prepared and tested in this process. The aldol product was achievable only by using the proline compound 4b, therefore different

• the diffusion through the membrane was not possible. Moreover, the crosslinking enabled stabilization of the enzymes, which remained active also after 10 days. Polymersome nanoreactors have also been used to perform many types of non-enzymatic catalytic reactions, such as the proline-catalyzed

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• stereocontrol in alcoholytic catalytic asymmetric desymmetrizations of meso-cyclic anhydrides is of special interest [1][2][3][4][5][6][7]. Major families originating from natural products include cinchona alkaloids [8][9][10][11][12][13][14][15][16][17] and proteinogenic α-amino acids such as proline [18][19

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

• TFA as promoter at 80 °C to 140 °C. A three-component reaction of 5-aminopyrazole 16, 4-hydroxycoumarin (50) and aldehydes 47 was studied by Liu et al. [55] in various solvents like acetonitrile, dichloromethane, toluene and DMSO in the presence of catalysts like ZrCl4, InCl3, FeCl3, L-proline etc

• catalysts like L-proline, InCl3 and ZrCl4 also resulted in the formation of o-hydroxyphenylpyrazolo[3,4-b]pyridine derivatives 85 but no product was formed in iodine- and acetic acid-catalyzed reactions (Scheme 22). Huang et al. [70] investigated a three-component reaction of β-ketonitriles 15, 5

• -1-(methylthio)-2-nitroethenamine (96) was studied by Gunasekaran et al. [77] (Scheme 28) in ethanol in presence of 30 mol % L-proline as catalyst at 78 °C which resulted in the production of pyrazolo[3,4-b]pyridine derivatives 97 in excellent yields. Jiang et al. [78] have investigated a microwave

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• in good yield starting from the N-benzylation of L-proline in the presence of KOH, then activation of the carboxylic acid functionality of 10 using SOCl2 at low temperature, followed by condensation with 2-aminobenzophenone (Scheme 2). Complexation of 11 with nickel nitrate and glycine under basic

Binding abilities of a chiral calix[4]resorcinarene: a polarimetric investigation on a complex case of study

• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2698–2709, doi:10.3762/bjoc.13.268

• Polarimetry was used to investigate the binding abilities of a chiral calix[4]resorcinarene derivative, bearing L-proline subunits, towards a set of suitably selected organic guests. The simultaneous formation of 1:1 and 2:1 host–guest inclusion complexes was observed in several cases, depending on both the

• can be generally achieved by linking suitable donor groups to the aromatic scaffold. Among the virtually countless examples available in recent literature, L-proline-modified CAs constitute an interesting subject of study [19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Proline-based systems

• in general have been proven excellent stereoselective organocatalysts [33][34][35][36][37][38][39][40]. In particular, CA derivatives bearing proline units (on both the upper and the lower rim) have been tested as catalysts for asymmetric aldol reactions in water [28][29][30][33]. Similar derivatives

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

• fluorescence push–pull system would be destroyed. To confirm this, we modified 1 to provide a peptidic substrate for an enzyme. The serine protease DPP-4 was used as the test enzyme because its substrate specificity is clear: it hydrolyses the C-terminal of proline or alanine second to the N-terminal of the

• -protected glycine was condensed with proline methyl ester under microwave irradiation. Subsequent hydrolysis of the ester gave N-protected Gly-Pro-OH (6). Condensation of dipeptide 6 with 1 was achieved using the corresponding acid chloride. Deprotection of the amino group was achieved by treatment with

• ]-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