Conformational study of L-methionine and L-cysteine derivatives through quantum chemical calculations and ³J_HH coupling constant analyses

• Weslley G. D. P. Silva,
• Carolyne B. Braga and
• Roberto Rittner

Beilstein J. Org. Chem. 2017, 13, 925–937, doi:10.3762/bjoc.13.94

• derivatives of tryptophan [20], phenylalanine and tyrosine [21], aspartic acid [22], proline [23] and histidine [24]. These studies have provided significant results to understand the importance of the corresponding amino acids in processes in which they take part in the polypeptide chain. Furthermore, these

Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction

• Yan Chen,
• Xiaoman Wang,
• Junchang Wang and
• You Yang

Beilstein J. Org. Chem. 2017, 13, 795–799, doi:10.3762/bjoc.13.79

• L-proline at room temperature for three days proceeded sluggishly, leading to the desired product in a very low yield. Gratifyingly, when the L-proline-catalyzed aldol reaction was performed at 70 °C for one day, the TLC indicated the complete consumption of aldehyde 3, and the generated 4,5-anti

• excellent anti-selectivity for the L-proline-catalyzed aldol reaction can be explained by the Houk–List transition state model [43][44][45]. Compound 13 was then acetylated to afford differentially protected ketoheptose building block 2 in 83% yield. The structure of 2 was unambiguously confirmed by 1H, 13C

Ultrasound-promoted organocatalytic enamine–azide [3 + 2] cycloaddition reactions for the synthesis of ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones

• Gabriel P. Costa,
• Natália Seus,
• Juliano A. Roehrs,
• Raquel G. Jacob,
• Ricardo F. Schumacher,
• Thiago Barcellos,
• Rafael Luque and
• Diego Alves

Beilstein J. Org. Chem. 2017, 13, 694–702, doi:10.3762/bjoc.13.68

• , entries 9 and 10). Reactions performed with other catalysts (L-proline and pyrrolidine) gave lower yields of 3a than those using 1 mol % of Et2NH (Table 1, entry 7 vs entries 11 and 12). From Table 1, optimum reaction conditions to obtain 1-(5-methyl-1-(2-(phenylselanyl)phenyl)-1H-1,2,3-triazol-4-yl)ethan

Synthesis of new pyrrolidine-based organocatalysts and study of their use in the asymmetric Michael addition of aldehydes to nitroolefins

• Alejandro Castán,
• Ramón Badorrey,
• José A. Gálvez and
• María D. Díaz-de-Villegas

Beilstein J. Org. Chem. 2017, 13, 612–619, doi:10.3762/bjoc.13.59

• selected as a benchmark reaction to study their behaviour as organocatalysts. Compounds with a related structure prepared from proline by Diez et al. have proven to work well as organocatalysts in the Michael addition of cyclohexanones to nitrostyrenes [19][20]. We first tested organocatalysts OC1–OC4 in

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• combination of CuI and bidentate ligand could promote the conversion of aryl halides to the corresponding phenols in a mixed solvent system of DMSO/H2O (1:1). Using iodobenzene as model substrate, various ligands were successfully tested: L-proline (yield 70%), 2-hydroxyacetophenone (yield 85%), N,N-dimethyl

• , the Qi group reported a similar protocol to achieve the coupling of aryl iodides and thiourea by CuI/L-proline-catalyzed reaction in the presence of Cs2CO3 as base in DMSO [98]. In 2004, the Itoh group demonstrated that Pd2(dba)3/Xantphos (L14) could catalyze the coupling of aryl halides and aryl or

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• ability, chromophoric properties, and antitumor activity as well [40]. We compared several CuI-based catalytic systems in the arylation of amine 3b with 4-iodotoluene as a model substrate. We found out that the CuI/L-proline combination with K2CO3 led to the target aniline 4 in excellent yield (Scheme 3

• anthraquinones. Further attempts to apply the Cu-based catalytic system in this reaction with L-proline and other commonly used N,N, N,O, and O,O bidentate ligands were fruitless. Previously, some of us successfully used the classic conditions of the Buchwald–Hartwig amination for the preparation of bis-amino

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• tricyclic skeleton that bears a newly formed pyrrolidine, similar to proline. The post-translational dimethylallylation of two tryptophan residues of a cyclic peptide, kawaguchipeptin A, from cyanobacteria has also been reported. Interestingly, the modified tryptophan residues of kawaguchipeptin A have the

• either a geranyl or farnesyl group at the gamma position to form tricyclic skeleton that bears a newly formed pyrrolidine, which is similar to proline (Figure 3A) [26][27][28]. The posttranslational modification of ComX pheromones with an isoprenoid plays an essential role for specific quorum sensing

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• stereospecific cyclic adducts. Keywords: L-proline; ninhydrin; sarcosine; spiropyrrolidine; 5-vinylindazole; 5-vinylindole; Introduction The [3 + 2] cycloaddition between azomethine ylides and olefins/acetylene as dipolarophiles is an important reaction to access a number of novel heterocyclic spiro scaffolds

• in the construction of functionalized spiro compounds. We report herein the facile synthesis of novel spiropyrrolidine compounds through a one-pot three-component reaction involving N-substituted vinylindole/indazole, ninhydrin and sarcosine/L-proline. The present multicomponent reaction (MCR) leads

• cyclic amino acid L-proline (6) which was reacted with 3 under the optimized reaction conditions. The corresponding stereo- and regiospecific isomers of spiropyrrolidines 8 were obtained in good yields (Table 1, entries 12–22). The stereochemical assignments for compounds 8 were supported by 2D NMR data

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• ., alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophan, cysteine and methionine), they can be easily included inside the CDs. This complexation leads to modification of the protein. For sake of clarity, only some typical examples are reported in this section. In their paper on the

Towards the development of continuous, organocatalytic, and stereoselective reactions in deep eutectic solvents

• Davide Brenna,
• Elisabetta Massolo,
• Alessandra Puglisi,
• Sergio Rossi,
• Giuseppe Celentano,
• Maurizio Benaglia and
• Vito Capriati

Beilstein J. Org. Chem. 2016, 12, 2620–2626, doi:10.3762/bjoc.12.258

• synthesis of enantiomerically enriched products by testing different experimental set-ups. L-Proline-catalysed cross-aldol reactions were efficiently performed in continuo, with high yield (99%), anti-stereoselectivity, and enantioselectivity (up to 97% ee). Moreover, using two different DES mixtures, the

• . Keywords: continuous process; DES; organocatalysis; proline; stereoselective aldol reaction; Introduction The aldol reaction is a powerful synthetic tool to create new C–C bonds [1]. It offers several possibilities to control the stereochemical outcome of the process and to afford stereochemically defined

• chiral products [2]. Among all the possible options, the L-proline-catalysed stereoselective cross-aldol reaction remains the greener choice. After the pioneering works by List and Barbas [3], a huge effort was made by the scientific community to improve both the yield and the stereoselectivity of the

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• -enduracididine by Yuan et al.: In 2015, Yuan et al. reported their synthesis of protected L-allo-enduracididine 63 from L-4-hydroxyproline 64 (Scheme 12) [66]. The C-4 stereocentre was installed through inversion of the hydroxy group of proline derivative 64 via mesylation and azide displacement to afford 65

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• explore the structural diversity using different p-nitrophenyl carbonates which were prepared by treating an alcohol with p-nitrophenyl chloroformate in CH2Cl2 using pyridine as a base. Thus, homopropargyl alcohol, decanol, cholesterol and N-Boc-trans-4-hydroxy-L-proline methyl ester gave the

• -caprolactam of N-Boc-trans-4-hydroxy-L-proline methyl ester 5b, rotamers due to flipping of the N-Boc group were obtained. Owing to the importance of sugar caprolactams in polymerizations, 2,3-di-O-benzyl-4-O-p-methoxybenzyl-α-methyl-D-glucopyranoside and 2,3,4-tri-O-benzoyl-α-methyl-D-glucopyranoside [30][31

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• )-alkoxyamine 123. The reaction of the L-proline derivative 124 and its analogues 125 and 126 with cyclohexadiene (120) gave relatively low de values [112] (Scheme 25). A more comprehensive study on amino acid based acylnitroso dienophiles was performed by Miller et al. [28][113]. For a number of L- and D-amino

• acids and derivatives 129, including proline-derived dienophiles, the stereoselectivity of the reaction with cyclopentadiene (130) was tested, and again only a modest size-dependent (R1) stereoselectivity was found for the products 131 (Table 3). Some more extensive studies on reactions of proline or

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• moiety of the substrate [26]. Mutation within these conserved motifs is usually critical for enyzme functionality [26][41]. The (−)-α-amorphene synthase from S. viridochromogenes DSM 40736 displays the aspartate-rich motif (105DDRAE), the NSE triad (242PDLFSAVKE) starting with a proline instead of the

• usual asparagine, obviously without effect on the enzyme function, the pyrophosphate sensor R-196 and the 327RY dimer. Terpene cyclases with close homology are encoded in more than 40 genome sequenced streptomycetes that all show an altered NSE triad starting with either proline or alanine. The closest

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• asymmetric Mannich reaction using a Lewis acid catalyst [1]. (L)-Proline is known as an excellent promoter for the Mannich reaction [2][3][4][5][6], and besides this, the reaction of the silyl enol ether derivatives with imines was used as an effective method [7][8][9]. In this situation, a wide variety of

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• ]. The desired phosphono-substituted pyrroles were isolated in 41–87% yield under solvent and catalyst-free conditions. Kaboudin et al. described a three-component, catalyst-free decarboxylative coupling of proline (296) with aldehydes 297 and dialkyl phosphonates to afford pyrrolidinylphosphonates 300

• . The corresponding pyrrolidinylphosphonates 300 were isolated in 43–86% yields under refluxing in toluene (Scheme 61) [99]. The reaction was proposed to proceed through the condensation of proline with an aldehyde under formation of oxazolidin-5-ones 298 followed by decarboxylation to give the

• proline with aldehydes and dialkyl phosphites for the synthesis of pyrrolidinylphosphonates. Three-component domino aza-Wittig/phospha-Mannich sequence for the phosphorylation of isatin derivatives. Stereoselective synthesis of phosphorylated trans-1,5-benzodiazepines via a one-pot three-component

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• proline and its derivatives [31]. Recently, Hoveyda and co-workers designed a novel amino acid amide catalyst (cat. 4) for the asymmetric addition of unsaturated organoboranes to carbonyls and imines, producing the corresponding enantiomerically pure alcohols and amines in excellent yields [32]. As shown

• cyanomethylation of isatins with cyanoacetic acid using the L-proline-derived thiourea as the catalyst (cat. 30), giving the cyanomethylated products in good yields (up to 82%) and with excellent enantioselectivities (up to 90% ee, Scheme 44) [61]. The reactions were performed in methyl tert-butyl ether at room

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

• (Scheme 2, compounds 13–15) proceeded with poor diastereocontrol but the results were improved by changing to catalyst C2 [62]. Nonetheless, in both cases the enantioselectivity for the major diastereomer was excellent. Finally, and starting from the corresponding bicyclic imidazolones, quaternary proline

Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• other aromatic amino acids, such as phenylalanine or tyrosine (products 5c and 5d). Serine and proline containing dipeptides 5e and 5f could also be obtained in 64% and 53% yield, respectively. The reaction was therefore general for dipeptides bearing tryptophan at the C-terminus. On the other hand

cis–trans-Amide isomerism of the 3,4-dehydroproline residue, the ‘unpuckered’ proline

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2016, 12, 589–593, doi:10.3762/bjoc.12.57

• Vladimir Kubyshkin Nediljko Budisa Institute of Chemistry, Technical University of Berlin, Müller-Breslau-Str., 10, 10623, Berlin, Germany 10.3762/bjoc.12.57 Abstract Proline (Pro) is an outstanding amino acid in various biochemical and physicochemical perspectives, especially when considering

• isomerism; fluorine; pKa; proline; Introduction The sole genetically encoded secondary amino acid proline (Pro, 1) is known for its unique properties in biological systems. In particular, Pro residues are often found in the s-cis peptidyl-Pro conformation, due to the low energy difference between the s

• reasons. However, it has also been reported that N-acylated pyroglutamic acid exhibits almost exclusively the s-trans amide conformation despite being formally a 5-substituted Pro [22]. The conformational preferences of the heterocyclic analogues of proline [23][24][25] and, in particular, pseudoprolines

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• incorporated into proline derivatives has been scarcely explored. Herein, the most representative and illustrative examples are compiled and this review will be mainly focused on the cases where the aminoindanol moiety confers bifunctionality to the organocatalysts. Keywords: aminocatalysis; 1,2-aminoindanol

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• of intermediates have been proposed to be the reactive intermediates in many reactions such as aldol, Michael, Mannich, and α-functionalization (α-chlorination, α-amination, α-fluorination) reactions. Proline-type organocatalysts are considered priviliged, because their corresponding enamines exist

• enolate of cyclohexanone. Two subsequent aldol reactions furnished the desired product. Miscellaneous thiourea-catalysts and catalytic systems promoting asymmetric transformations that lead to a six-membered ring The discovery of L-proline as an organocatalyst for the aldol reaction was of major

• importance and therefore many asymmetric reactions that could not be achieved, are now possible. There are many reactions catalyzed by L-proline, affording stereoselective products in high yields and enantiomeric excess, nevertheless there are many limitations. For that reason, it has emerged the need for

Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

• Samantha Caputo,
• Andrea Basso,
• Lisa Moni,
• Renata Riva,
• Valeria Rocca and
• Luca Banfi

Beilstein J. Org. Chem. 2016, 12, 139–143, doi:10.3762/bjoc.12.15

• -Boc imines 2 and catalytic L-proline [29][30], followed by reduction of 3 and cleavage of the Boc group. This short and straightforward synthesis allows the introduction of 2 diversity inputs (R1 and Ar), whereas stereochemical diversity can also be explored using D-proline or different, anti

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• et al. [39] has been the only example of this type of catalytic asymmetric coupling reaction. They reacted 2-halotrifluoroacetanilides with 2-methylacetoacetates under the catalysis of CuI/trans-4-hydroxy-L-proline and obtained the arylated products in good yields and enantioselectivities. In this