Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• acetylene-functionalized Thermomyces lanuginosus lipase was then attached to these azide-functionalized water-soluble AuNPs by CuAAC (Scheme 7). It was found that the enzyme retained its activity after the click reaction. However, the vast excesses of both Cu (a one million-fold excess relative to the azide

• ) and lipase needed, the long reaction time (3 days), the extensive purification procedure required, and the poor overall conversion of azide to triazole (less than 1%) limited any further use of this procedure. In 2007, Sommer and Weck developed a simpler and more efficient method to perform CuAAC on

• polymersomes and strained alkyne-functionalized AuNPs (DBCO-AuNPs) in water [57]. Functionalization of AuNPs with an azide containing thiol ligand, and subsequent attachment to an acetylene-functionalized lipase by CuAAC. Reagents and conditions: (a) H2O, rt, 18 h; (b) H2O, CuSO4, ascorbic acid, rt, 3 d. [47

Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279

• assay [30]. Substitution of tryptophan, tyrosine, and phenylalanine residues in a glycosylation-deficient mutant of Candida antarctica lipase B, CalB N74D, by their monofluorinated analogues, left the resistance to proteolytic degradation by proteinase K unchanged [31]. Incorporation of α-fluoroalkyl

Correction: Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 2128–2130, doi:10.3762/bjoc.13.210

• . Universidad 1001, Cuernavaca, Morelos, 62210, Mexico El Colegio Nacional, Luis Gonzáles Obregón 23, Centro Histórico, Ciudad de México, 06020, Mexico 10.3762/bjoc.13.210 Keywords: ball-milling; β3-amino acid; Candida antarctica lipase B; enzymatic resolution; mechanochemistry; The original published Tables

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides

• Neha Rana,
• Manish Kumar,
• Vinod Khatri,
• Jyotirmoy Maity and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2017, 13, 2078–2086, doi:10.3762/bjoc.13.205

• : bicyclonucleosides; biocatalysis; lipase; Novozyme®-435; separation of epimers; Introduction Sugar-modified bicyclic nucleosides have drawn the attention of synthetic chemists because of their effect on the conformational restriction of the furanose moiety of the nucleoside [1][2][3][4][5][6][7][8][9]. The

• hydroxy groups present in different sugars and sugar moieties of synthetic or naturally occurring glycosides, nucleosides, etc. Gotor et al. [11] have reported a lipase-mediated acylation of an equimolecular mixture of D/L-thymidine with acetonoxime levulinate as acylating agent and Pseudomonas cepacia

• lipase as biocatalyst. Similar applications of lipases have been reported for the separation of mixtures of arabinofuranosyl and -pyranosyl nucleosides [12], O-aryl α,β-D-ribofuranosides, etc. [13][14][15]. We herein report for the first time the use of Novozyme®-435 for the separation of an epimeric

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• Ulla Weissbach Saumya Dabral Laure Konnert Carsten Bolm Jose G. Hernandez Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany 10.3762/bjoc.13.173 Abstract A lipase-catalyzed esterification of lignin model compounds in the ball mill was developed combining

• (Scheme 1a) [8]. Similarly, immobilized lipases (triglycerol acylhydrolases EC 3.1.1.3) such as Amano lipase PS-IM from Burkholderia cepacia immobilized on diatomaceous earth and lipase B from Candida antarctica (expressed in Aspergillus niger) adsorbed on polymethacrylate beads (ca. 400 μm–600 μm in

• diameter) [9], demonstrated to efficiently mediate the enzymatic kinetic resolution of secondary alcohols under solvent-free conditions in both mixer and planetary ball mills (Scheme 1b) [10]. Interestingly, this latter lipase (a commercial preparation known as Novozyme 345, hereinafter referred as CALB

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• resolution of racemic β3-amino esters employing Candida antarctica lipase B (CALB) to afford highly valuable enantioenriched N-benzylated-β3-amino acids in good yields. Furthermore the present protocol is readily scalable. Keywords: ball-milling; β3-amino acid; Candida antarctica lipase B; enzymatic

• ][18][19][20][21][22] including strategies based on organocatalysis [23][24][25][26] and kinetic resolution using enzymes such as Candida antarctica lipase B, which was shown to be efficient in the resolution of racemic β-amino acids under various conditions [27][28][29][30]. Among recent developments

• applications on a large scale [45][46]. Very recently, Hernández, Frings, and Bolm developed a method to carry out the kinetic resolution of secondary alcohols through selective acylation using Candida antarctica lipase B, under solvent-free ball-milling conditions [47][48]. Inspired by this ground-breaking

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• debenzoylated or deacetylated using standard conditions (NaOMe/MeOH) nearly quantitatively and then covalently linked to several electrophiles, including proteins. Shown in Scheme 26 is the cross-linking of 1-thiohexahyaluronane (HA-6-SH) to a protein, the engineered thermostable lipase TTL from

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• diastereocontrol (dr >98:2). Subsequent enzymatic desymmetrization [91] using lipase Amano AK gave the enantiomerically pure acetate 36 in 81% yield (ee >99%). A further three transformations then delivered cis-solamin A (29). Crucial to the success of this approach and its high efficiency is that it takes

Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates

• Maurizio Selva,
• Alvise Perosa,
• Sandro Guidi and
• Lisa Cattelan

Beilstein J. Org. Chem. 2016, 12, 1911–1924, doi:10.3762/bjoc.12.181

• -value chemicals. This holds true also for enzyme-catalyzed transesterification reactions. To cite a few examples, the literature claims the use of lipase as a biocatalyst for i) the reaction of glycerol with DMC for the synthesis of glycerol carbonate (GlyC) under solvent-free conditions. A 60% yield

• ], and iii) the conversion of oils for which lipase was identified as the most suitable enzyme for an innovative and green production of biodiesel [19]. Other catalytic systems: In addition to the above-described catalysts, amines and organometallic derivatives also find applications in the field of

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• -von-Laue-Straße 7, D-60438 Frankfurt am Main, Germany 10.3762/bjoc.12.176 Abstract Starting from (S)-β-phenylalanine, easily accessible by lipase-catalyzed kinetic resolution, a chiral triamine was assembled by a reductive amination and finally cyclized to form the title compound 10. In the crystals

• chemical correlation. Keywords: absolute configuration; anthrone; cycloaddition; kinetic resolution; lipase; Introduction In guanidinium ions charge delocalization is an important factor to stabilize the protonated form. As a result, guanidines are exceptionally strong nitrogen bases. As part of the

• ][21]. A kinetic resolution of the enantiomers was achieved by enzymatic hydrolysis with Amano lipase PS from Burkholderia cepacia [22][23], a method already optimized for technical use [24]. The best results were obtained with methyl tert-butyl ether as a cosolvent [24]. By simple precipitation

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• of the β-hydroxy group on the thioester of 200, resulting in the off-loaded ebelactone A (201) (Scheme 28) [163]. The β-lactone moiety of the human pancreatic lipase inhibitor lipstatin is also formed in a similar fashion. 2 Nitrogen-containing heterocycles Nitrogen-containing heterocycles are

Chiral Cu(II)-catalyzed enantioselective β-borylation of α,β-unsaturated nitriles in water

• Lei Zhu,
• Taku Kitanosono,
• Pengyu Xu and
• Shū Kobayashi

Beilstein J. Org. Chem. 2015, 11, 2007–2011, doi:10.3762/bjoc.11.217

• desired β-borylated product was isolated as the β-hydroxynitrile after subsequent oxidation, with complete retention of the expected stereochemistry. β-Hydroxynitriles, which are conventionally synthesized by asymmetric addition of acetonitrile to aldehydes [6][20] or by lipase- or nitrilase-catalyzed

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• acids and their derivatives (esters and anhydrides) have been used as acylating agents in lipase-catalyzed reactions in organic solvents. The synthetic outcomes have been dimeric or hybrid derivatives of bioactive natural compounds as well as functionalized polyesters. Keywords: biocatalysis

• ; dicarboxylic acids; lipase; polyesters; regioselectivity; Introduction The finding that enzymes can work in organic solvents has significantly expanded the scope of preparative scale biocatalyzed transformations [1][2][3][4]. An uncountable number of reports have been published on this topic since the

• in the esterification of the antineoplastic antibiotics mithramycin (5) catalyzed by Candida antarctica lipase A (CAL-A) and chromomycin A3 (6) catalyzed by Candida antarctica lipase B (CAL-B) [24]. In another report a series of mono-substituted troxerutin esters (7a) were synthesized by action of

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• (CuAAC) and oxime ligation. This method was applied to the conjugation of biotin and β-linked galactose residues to yield an enzymatically active thermophilic lipase, which revealed specific binding to Erythrina cristagalli lectin by SPR binding studies. Keywords: chemoselectivity; dual protein

• paper was the development of a robust synthetic methodology that allows the site-specific attachment of two distinct chemical modifications to a given protein, which can be used to target multivalent interactions. As a protein scaffold we selected the thermophilic lipase from Thermoanaerobacter

• resolution of the MALDI for proteins all detected mass values differ by a few Dalton from the theoretical masses, and the peak intensity for the functionalized biotinylated lipase (Gal-0) was usually lower in all MALDI spectra which was addressed to the lower detectability of Gal-0 due to the attached biotin

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• chemoenzymatic route. The central chiral building block, 1-(10H-phenothiazin-10-yl)propan-2-ol, was obtained via a lipase-mediated kinetic resolution protocol, which furnished both enantiomeric forms, with superb enantioselectivity (up to E = 844), from the racemate. Novozym 435 and Lipozyme TL IM have been

• columns. Keywords: ethopropazine; lipase-catalyzed kinetic resolution; Mosher methodology; promethazine; stereodivergent synthesis; Introduction Since enantiomorphs of biologically active compounds exhibit significant differences in their pharmacokinetic and pharmacodynamic behavior, optical purity of

• know, been deemed insufficient. We believe that the lipase-catalyzed resolution procedure presented herein, will be an interesting alternative to these published methods, and will open a novel route worth considering in multigram-scale synthesis of both aforementioned pharmaceuticals. Therefore, the

A green approach to the synthesis of novel phytosphingolipidyl β-cyclodextrin designed to interact with membranes

• Yong Miao,
• Florence Djedaïni-Pilard and
• Véronique Bonnet

Beilstein J. Org. Chem. 2014, 10, 2654–2657, doi:10.3762/bjoc.10.278

• with a promising yield. Keywords: fatty ester; green chemistry; lipase; mono-substituted amphiphilic cyclodextrins; peptide Coupling; solvent-free medium; transesterification; Introduction Cyclodextrins (CDs) are sustainable compounds which are particularly interesting in the frame of pharmaceutical

cis–trans Isomerization of silybins A and B

• Michaela Novotná,
• Radek Gažák,
• David Biedermann,
• Florent Di Meo,
• Petr Marhol,
• Marek Kuzma,
• Lucie Bednárová,
• Kateřina Fuksová,
• Patrick Trouillas and
• Vladimír Křen

Beilstein J. Org. Chem. 2014, 10, 1047–1063, doi:10.3762/bjoc.10.105

• ], and at the preparatory scale by lipase-catalyzed discrimination [4][5]. However, chromatographic separation of 2,3-cis- and 2,3-trans-silybins is feasible after their C-23 O-acetylation, which can be accomplished with Novozym 435 in an acetone/vinyl acetate mixture, giving a nearly quantitative yield

• diastereoisomers were separated by lipase-catalyzed discrimination [5]. Candida antarctica lipase B (Novozym 435) was from Novozymes (DK). All other reagents were of analytical grade and used without further purification. (2R,3S,10R,11R)-23-O-Acetylsilybin (12): BF3·OEt2 (2 mL, 15.926 mmol, 50% solution in OEt2

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• to get (−)-gigantamide by lipase catalyzed kinetic resolution in line with the reported method for R-jatropham [23] was not successful. Conclusion In conclusion, a facile synthesis of (±)-grandiamide D (5), dasyclamide (6) and gigantamide A (7) and asymmetric synthesis of natural (+)-grandiamide D (5

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• . Fluorination has also been shown to influence reactivity in four-membered N-heterocycles (Scheme 1). Kanerva and co-workers [18] investigated a series of β-lactam derivatives (4a–c) in a lipase-catalysed methanolysis process. While the non-fluorinated derivative 4a was found to be unreactive under the reaction

• then furnished rac-4b, the substrate for enzymatic resolution. Using an immobilized lipase enzyme as the catalyst (and under slightly different conditions from those described in Scheme 1), one enantiomer of the racemic β-lactam 4b was completely transformed into the ester 5b, while the other

• . Fluorination makes β-lactam derivatives more reactive towards lipase-catalysed methanolysis. Hyperconjugation rigidifies the ring pucker of a fluorinated organocatalyst 14, leading to higher enantioselectivity. General strategy for the synthesis of fluorinated N-heterocycles via deoxyfluorination. During the

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• utilise acyl-SNACs provides the possibility to employ feeding studies to introduce new chemistry at C-8. AntO is a lipase homologue and is predicted to install the N-formyl group resulting in the 3-formamidosalicylate moiety. AntO is required for bioactivity against the human pathogenic fungus, Candida

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• carboxylic acid and (iii) a Ru–lipase-catalyzed dynamic kinetic resolution to establish the desired configuration at C9. Ring closure was accomplished by macrolactonization. Curvulide A was synthesized from stagonolide E through Sharpless epoxidation. Keywords: dienes; enzyme catalysis; lactones; metathesis

• /transition metal-catalysed approach was investigated [48][49]. In this regard, the combination of Ru complexes such as Shvo’s catalyst (C) [50], the amino-Cp catalyst D [51], or [Ru(CO)2Cl(η5C5Ph5)] [52], and the lipase novozym 435 has emerged as particularly useful [53][54]. We tested Ru catalysts C and D

• -diene-3,4-diol. Key elements of the stagonolide E synthesis are the two-directional functionalization of the enantiopure, C2-symmetrical starting material through cross metathesis and a one-flask ring-closing metathesis/base-induced ring-opening sequence, a Ru–lipase-catalyzed dynamic kinetic resolution

A protecting group-free synthesis of the Colorado potato beetle pheromone

• Zhongtao Wu,
• Manuel Jäger,
• Jeffrey Buter and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2013, 9, 2374–2377, doi:10.3762/bjoc.9.273

• . Although the approach is elegant, (S)-linalool required for natural (S)-1 is not commercially available. In 2005, Mori employing lipase-catalyzed kinetic resolution of (±)-2,3-epoxynerol as the key step, synthesized both (S)- and (R)-1 in gram quantities with high ee. In Chauhan’s work, Grignard reaction

Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids

• Paweł Borowiecki,
• Małgorzata Milner-Krawczyk and
• Jan Plenkiewicz

Beilstein J. Org. Chem. 2013, 9, 516–525, doi:10.3762/bjoc.9.56

• -propylene oxide with imidazole or 1,2,4-triazole. Lipase-catalyzed transesterification of alcohols with vinyl acetate resulted in kinetic enantiomers resolution. Separated (S)-enantiomers of (+)-1-(1H-imidazol-1-yl)propan-2-ol and (+)-1-(1H-1,2,4-triazol-1-yl)propan-2-ol were quaternized with alkyl bromides

• bacteria and fungi. Results and Discussion Synthesis and enzymatic resolution of the N-2-hydroxypropylazoles In this paper we report the synthesis of racemic 1-(1H-imidazol-1-yl)propan-2-ol and 1-(1H-1,2,4-triazol-1-yl)propan-2-ol and the procedure for lipase-catalyzed kinetic separation of their

• ). Next, these compounds were used as a new type of substrate in lipase-catalyzed transesterification, yielding both enantiomers with good optical purity. The syntheses of the secondary alcohols (±)-3a and (±)-3b were accomplished by the addition of imidazole (2a) or 1,2,4-triazole (2b) to 1,2-propylene

Restructuring polymers via nanoconfinement and subsequent release

• Alan E. Tonelli

Beilstein J. Org. Chem. 2012, 8, 1318–1332, doi:10.3762/bjoc.8.151

• containing lipase from Rhizopus arrhizus by means of ultraviolet and attenuated total reflectance FTIR spectroscopy, DSC, wide-angle X-ray diffraction, and weight-loss analysis. The PCL segments in all of the above films were found to degrade much faster than the PLLA segments. As expected, suppression of