1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• , however, very few of them provide N-substituted derivatives directly [54]. In this context, 1H-imidazol-4(5H)-ones 1 have been recently introduced as novel nucleophilic α-amino acid equivalents for the catalytic and asymmetric synthesis of N-alkyl, N-aryl and N-allyl α,α-disubstituted amino acids [55

• to an additional stereodirecting group. Following this design and starting from the corresponding N-protected α-amino acid 46 different catalysts were easily synthesized by the reaction of the respective intermediate isocyanates 47 [93] with 9-epi-9-amino-9-deoxyquinine or 9-epi-9-amino-9

Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

• M. Fernanda N. N. Carvalho,
• M. João Ferreira,
• Ana S. O. Knittel,
• Maria da Conceição Oliveira,
• João Costa Pessoa,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2016, 12, 732–744, doi:10.3762/bjoc.12.73

• (200 μL) was added to the suspension of oxoimine 1 (0.23 g, 1.01 mM) in EtOH (5 mL) and the mixture was stirred at 45 °C for 0.25 h. Then, the α-amino acid (glycine; L-alanine; L-phenylalanine; leucine) in ca. 2.5 stoichiometric excess was dissolved in H2O (ca. 4 mL, 60 °C) and added. The suspension

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• ) in the α-hydroxylation of indenones (where n = 1 in 77) using cumyl hydroperoxide (Scheme 19) [58]. Interestingly, the 3,4-dihydronaphthalen-1(2H)-one derivative (where n = 2 in 77) did not afford any detectable product. Transamination A range of α-amino acid derivatives have been accessed by Shi and

Asymmetric α-amination of β-keto esters using a guanidine–bisurea bifunctional organocatalyst

• Minami Odagi,
• Yoshiharu Yamamoto and
• Kazuo Nagasawa

Beilstein J. Org. Chem. 2016, 12, 198–203, doi:10.3762/bjoc.12.22

• important synthetic route to optically active α-amino acid derivatives with chiral quaternary stereocenters [1][2]. Since an α-amino acid moiety is frequently found in biologically active compounds, considerable efforts have been made to achieve a stereoselective synthesis of this structure [3][4]. In

A new method for the synthesis of α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues

• Anna Kuźnik,
• Roman Mazurkiewicz,
• Mirosława Grymel,
• Katarzyna Zielińska,
• Jakub Adamek,
• Ewa Chmielewska,
• Marta Bochno and
• Sonia Kubica

Beilstein J. Org. Chem. 2015, 11, 1418–1424, doi:10.3762/bjoc.11.153

• failed, probably due to the steric hindrance exerted by a bulky substituent at the α-position. Electrochemical α-alkoxylation of N-acyl-α-amino acid esters mediated by NaCl, NaBr, LiCl, KCl or KI is a well-known reaction [38][42][43][44][45][46], whereas the analogous reaction of N-acyl-α-aminophosphonic

• phosphinites in the presence of Hünig’s base and methyltriphenylphosphonium iodide in a Michaelis–Arbuzov-like reaction to give the expected alkylidenebisphosphonates, 1-phosphinylalkylphosphonates or 1-phosphinoylalkylphosphonates, respectively, in good yields. Keywords: alkylidenebisphosphonate; α-amino

• acid phosphorus analogues; electrochemical α-methoxylation; 1-phosphinoylalkylphosphonate; 1-phosphinylalkylphosphonate; Introduction α-Aminophosphonic and α-aminophosphinic acids, as phosphorus analogues and bioisosters of α-amino acids, exhibit a variety of important biological properties [1][2][3

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• R1 and R2. In both cases, a second electron reduction in presence of CO2 yields a carboxylate intermediate with an additional carbonate or carbamate group. The latter is converted to the corresponding α-hydroxy acid or to an α-amino acid after acid hydrolysis in the product work-up [75][76][77]. An

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

• yields and ee’s. In 2007, based on their peptide catalyst studies, the Miller group developed the first α-amino acid-based phosphine catalyst H1 for enantioselective [3 + 2] annulations of allenoates with enones (Scheme 21) [52]. This catalyst performed multiple roles during the catalytic process, with

One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular S_N2 reaction

• Yiwen Xiong,
• Ping Qian,
• Chenhui Cao,
• Haibo Mei,
• Jianlin Han,
• Guigen Li and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 1802–1807, doi:10.3762/bjoc.10.189

• corresponding β,γ-amino alcohols and vicinal diamines. α,β-Diamino acid derivatives have been served as organocatalysts, chiral ligands, chiral auxiliaries for asymmertric synthesis [10][11][12], as well as synthetic fragments for peptides and natural products [13]. Mannich-type addition reactions of α-amino

• acid derivatives with imino compounds, or their precursors, is one of the most straightforward synthetic approaches to α,β-diamino acid compounds, in particular in asymmetric mode [14][15][16][17][18][19][20][21][22]. Direct catalytic oxidative diaminations of functionalized alkenes also present an

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• substrate afforded nucleosides 30 bearing a N-acyl α-amino acid amide moiety at the uracil C-5 carbon atom (Scheme 14) [79]. The variant of the reaction with trimethylsilyl azide (TMS-N3) in place of the carboxylic acid gave the tetrazole-substituted nucleosides 31 [79]. Products 30 and 31 were obtained as

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• develop a method for the modification of the acyl side chain of a previously incorporated O-acylated β-hydroxy-α-amino acid building block at a very late stage and under mild conditions, e.g., by olefin cross metathesis. Therefore, amino alcohol 5 was Fmoc-protected (product 34, 84% yield), followed by

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

• Yiwen Xiong,
• Haibo Mei,
• Lingmin Wu,
• Jianlin Han,
• Yi Pan and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 653–659, doi:10.3762/bjoc.10.57

• ][2][3], because the ester group can serve as an activator to enhance the reactivity of the C=N double bond, thus making the following nucleophilic addition easier [4][5]. More attractively, the transformation of α-imino esters can provide an easy access to various natural and unnatural α-amino acid

• resulted α-amino acid derivatives are useful building blocks in modern organic synthetic and medicinal chemistry [21][22]. For example, we can easily find the active participation of α-imino esters in the total synthesis of the bioactive molecule fumimycin [23]. Moreover, α-amino acids are the most general

Tuning the interactions between electron spins in fullerene-based triad systems

• Maria A. Lebedeva,
• Thomas W. Chamberlain,
• E. Stephen Davies,
• Bradley E. Thomas,
• Martin Schröder and
• Andrei N. Khlobystov

Beilstein J. Org. Chem. 2014, 10, 332–343, doi:10.3762/bjoc.10.31

• nucleophilic substitution of the iodide centre in benzyl 2-iodoacetate [24] (13) with [60]fulleropyrrolidine 9 (Scheme 3). Compound 14 is a benzyl ester of an α-amino acid which is stable under acidic conditions. Indeed, deprotection of 14 yielded the desired carboxylic acid 15. Compound 15 also shows limited

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• acrylamides 3 in boiling aqueous methanol (1:3) afforded the spirooxindoles 4a–4g in moderate to excellent yields (Table 1). The reaction times largely depend on the reactivity of the employed α-amino acid. The longest reaction time (7 h) was found for sarcosine, while the fastest reaction (40 min) was found

• 22.9° and the shortest distance between carbon atoms (C6…C15) is 3.04 Å). The mechanism of the azomethine ylide formation by a decarboxylative route has been repeatedly described by a number of authors and is depicted in Scheme 1 [35][36]. The reaction between isatin and the α-amino acid affords the

• aroylacrylic acids 5 were prepared according to the previously reported procedure [42]. General procedure for the synthesis of spirooxindoles 4a–4g from the three-component reaction of isatins, sarcosine or cyclic α-amino acids and acrylamides: A mixture of isatin (1.0 mmol), α-amino acid (1.0 mmol) and

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• (azlactones) are suitable heterocycles to perform this C–C bond generation based strategy affording both quaternized and non quaternized α-amino acid derivatives [2][3][4][5]. The preparation of azlactones is very simple and their reactivity is very diverse due to their functional groups [2][3][4][5]. Many

• order to clarify the enantio- and anomalous regioselectivity. Results and Discussion Initially, the synthesis of oxazolones 5 was accomplished under mild reaction conditions by mixing N-acyl-α-amino acid derivatives in the presence of dehydrating agents such as carbodiimides [2][3][4][5]. Gold(I

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• (Scheme 16, A). Alternatively, the α-amino acid portion of 1.81 can be diazotised under standard conditions and will subsequently deliver the same product when treated with lithium isothiocyanate (Scheme 16, B). Finally, α-bromonitrile 1.77 can be condensed with thiourea to give pioglitazone after aqueous

Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

• Sosale Chandrasekhar and
• V. Mohana Rao

Beilstein J. Org. Chem. 2012, 8, 1393–1399, doi:10.3762/bjoc.8.161

• acid (possibly selectively). These conversions would be of considerable value in peptide synthesis strategy. Conclusion Rationally designed, controlled approaches to α-amino acid synthesis via two classical reactions have been demonstrated. The key step is based on the Beckmann and the Hofmann

Intramolecular bridges formed by photoswitchable click amino acids

• Christian Hoppmann,
• Ronald Kühne and
• Michael Beyermann

Beilstein J. Org. Chem. 2012, 8, 884–889, doi:10.3762/bjoc.8.100

• switches [1][2][3][4][5], the PSCaa described here (Scheme 1) is an α-amino acid containing, besides an azobenzene unit, a vinyl function that can react specifically with a cysteine within a putative conformational domain of a peptide or a protein by light-induced thiol–ene click reaction [6][7][8][9]. The

Fifty years of oxacalix[3]arenes: A review

• Kevin Cottet,
• Paula M. Marcos and
• Peter J. Cragg

Beilstein J. Org. Chem. 2012, 8, 201–226, doi:10.3762/bjoc.8.22

• was shown to exist in (+) and (−) enantiomers, and in a partial-cone conformation, proof of which came from X-ray crystallography. The compound bound to α-amino acid ethyl esters and 1-arylethylamines with the methoxy and one n-butoxy oxygen. The (−)-4-tert-butyloxacalix[3]arene derivative bound L

A straightforward approach towards combined α-amino and α-hydroxy acids based on Passerini reactions

• Ameer F. Zahoor,
• Sarah Thies and
• Uli Kazmaier

Beilstein J. Org. Chem. 2011, 7, 1299–1303, doi:10.3762/bjoc.7.151

• conclusion, we showed that the ring opening of epoxides, either directly or Pd-catalyzed, with chelated enolates combined with Passerini reactions is a suitable tool for the synthesis of highly functionalized α-hydroxy and α-amino acid derivatives. These new compounds are interesting building blocks for

Anthracene appended pyridinium amide–urea conjugate in selective fluorometric sensing of L-N-acetylvaline salt

• Kumaresh Ghosh,
• Tanmay Sarkar and
• Asoke P. Chattopadhyay

Beilstein J. Org. Chem. 2010, 6, 1211–1218, doi:10.3762/bjoc.6.139

• ; pyridinium amide–urea conjugate; Introduction The design and synthesis of artificial receptors capable of recognizing α-hydroxy and N-acetyl-α-amino acid carboxylates (i.e., salts of α-amino acids) is an active area of interest in supramolecular chemistry due to the biological significance and practical

Expanding the gelation properties of valine-based 3,5-diaminobenzoate organogelators with N-alkylurea functionalities

• Hak-Fun Chow and
• Chin-Ho Cheng

Beilstein J. Org. Chem. 2010, 6, 1015–1021, doi:10.3762/bjoc.6.114

• organogelation strength in aromatic solvents of a series of α-amino acid-based low molecular weight organogelators 1 (Figure 1) could be enhanced by appending additional aromatic-containing substituents [7]. Both the Cbz protecting group and the benzyl ester functionality were responsible for the enhanced

Synthesis of glycosylated β³-homo-threonine conjugates for mucin-like glycopeptide antigen analogues

• Florian Karch and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2010, 6, No. 47, doi:10.3762/bjoc.6.47

• bioavailability for tumour immunotherapy. Towards this end, TN and TF antigen conjugates O-glycosidically linked to Fmoc-β3-homo-threonine were prepared in good yield via Arndt–Eistert homologation of the corresponding glycosyl α-amino acid derivative. By incorporation of TN-Fmoc-β3hThr conjugate into the 20

Synthesis and binding studies of two new macrocyclic receptors for the stereoselective recognition of dipeptides

• Ana Maria Castilla,
• M. Morgan Conn and
• Pablo Ballester

Beilstein J. Org. Chem. 2010, 6, No. 5, doi:10.3762/bjoc.6.5

• present in the diamide series, selecting the α-amino acid-related hydrogen-bonding functionality. Only one of the two cyclic receptors shows modest signs of enantioselectivity and moderate diastereoselectivity in the recognition of the enantiomers and diastereoisomers of the Ala-Ala dipeptide (ΔΔG01 (DD

Synthesis of new C^α-tetrasubstituted α-amino acids

• Andreas A. Grauer and
• Burkhard König

Beilstein J. Org. Chem. 2009, 5, No. 5, doi:10.3762/bjoc.5.5

• oligopeptides of natural amino acids are often not suitable for structural studies, as drug candidates or as biological probes. One way to restrict the conformation and introduce rigidity is the use of Cα-tetrasubstituted α-amino acids, in which the α-hydrogen atom of the α-amino acid is replaced by an alkyl or