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

• starting materials for synthesis. For example, side-chain chemical manipulation of the most common α-amino acids is routinely preceded by protection of one or both of the amino acid functionalities. In addition to lengthening the synthetic sequence by adding auxiliary steps, protective groups for amino

• protective groups at the amino and carboxy termini of the amino acid (resulting in carbamate and/or ester protective groups) [4], as well as for the subsequent side-chain acylation. Relevant examples are too numerous to render possible any exhaustive or useful listing herein, but use of modern computerized

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• of the hemiacetal under these reaction conditions. Compound 9 was subjected to Zemplén transesterification with NaOMe in methanol to afford alcohol 10, and the hydrogenolytic removal of the remaining protective groups furnished the spacer-linked monomer 1 in excellent yield (Scheme 2). Chemical

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

• Michael Ghobrial,
• Marko D. Mihovilovic and
• Michael Schnürch

Beilstein J. Org. Chem. 2014, 10, 2186–2199, doi:10.3762/bjoc.10.226

• ). Product 7g was obtained in slightly better yield when replacing the Boc-PG with Cbz (Table 3, entry 7, 77%). Since both protective groups performed well, it was decided to use the Boc-PG for further investigations out of two reasons: i) the Boc group proved to be most efficient for iron-catalyzed

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• hydrogenolysis of this compound under conditions as above led to a complex product mixture and no product could be observed. An alternative method for N–O cleavage employs elemental zinc in the presence of acid [39], conditions that should simultaneously cleave the TBS protective groups. For the conversion of 21

• expected product 27 was obtained in 51% yield as a well soluble compound. The trityl protective groups enabled the deprotection of dimer 27 in one step. The O-trityl and N-benzyl groups were removed by hydrogenolysis under acidic conditions to obtain a mixture of compounds 28 and 29 (Scheme 13). As solvent

Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• % yield. With MurNAc building block 10 and 16 in hand, the solid-phase peptide synthesis of the MDP-antigen conjugates 2–5 was undertaken (Scheme 2). Commercially available Fmoc protected amino acids equipped with standard acid labile protective groups were used. The side chain of the C-terminal lysine of

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• palladium as a catalyst in the presence of tertiary amines as base. A variety of hydrophilic phosphines (102, 103) was synthesized. Since no protective groups were introduced, the method proves to be compatible with several functionalities. This methodology or in a slightly modified form has been used by

Tailoring of organic dyes with oxidoreductive compounds to obtain photocyclic radical generator systems exhibiting photocatalytic behavior

• Christian Ley,
• Julien Christmann,
• Ahmad Ibrahim,
• Luciano H. Di Stefano and
• Xavier Allonas

Beilstein J. Org. Chem. 2014, 10, 936–947, doi:10.3762/bjoc.10.92

• development of new methods for organic synthesis was achieved by use of photolabile protective groups, which could be released under irradiation by light [10][11]. Since many decades in industry, PRG are used in photopolymerization, a field in which the PRG prompt the initiation of the polymerization through

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

• Tatyana V. Abramova,
• Olga B. Morozova,
• Vladimir N. Silnikov and
• Alexandra V. Yurkovskaya

Beilstein J. Org. Chem. 2013, 9, 2898–2909, doi:10.3762/bjoc.9.326

• additional building block 15 to obtain conjugate 6 (Scheme 4). Keeping in mind the possibility of a further modification of fully protected derivative 31, we chose the acid labile MMTr protective group for the linker to obtain conjugate 7 because such protection is orthogonal to the protective groups of

• depended on the combination of the protective groups and a number of negatively and positively charged residues. Conjugate 1 Partly deprotected by the TBAF treatment conjugate 18 was treated with concentrated (25%) aqueous ammonia for 48 h at room temperature under stirring, and the mixture was evaporated

• TBAF treatment conjugate 33 was subjected to anion exchange chromatography as described for conjugate 1. The appropriate fractions were pooled and evaporated. The TFA and Ac protective groups were removed by concentrated (25%) aqueous ammonia treatment for 3 h. After evaporation, target product 8 was

The total synthesis of D-chalcose and its C-3 epimer

• Jun Sun,
• Song Fan,
• Zhan Wang,
• Guoning Zhang,
• Kai Bao and
• Weige Zhang

Beilstein J. Org. Chem. 2013, 9, 2620–2624, doi:10.3762/bjoc.9.296

• deprotected and oxidized to yield the corresponding aldehyde. Our first step toward this goal was to select appropriate protective groups. Diol 6 was initially converted into benzylidene derivative 8 (α,α-dimethoxytoluene/PPTS/CH2Cl2); 8 was subjected to a regioselective reductive ring-opening reaction [23

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• to the use of fully functionalized building blocks the desired product can be obtained directly after cleavage from the resin and after overall deprotection. In order to be suitable for solid-phase synthesis, the building blocks have to be soluble in DMF or NMP, permanent protective groups have to be

Bis(benzylamine) monomers: One-pot preparation and application in dendrimer scaffolds for removing pyrene from aqueous environments

• Olivia N. Monaco,
• Sarah C. Tomas,
• Meghan K. Kirrane and
• Amy M. Balija

Beilstein J. Org. Chem. 2013, 9, 2320–2327, doi:10.3762/bjoc.9.266

• without the need for protective groups or purification. This monomer preparation is universal for various electron-donating and electron-withdrawing benzaldehyde substrates. To demonstrate the versatility of these previously unreported AB2 monomers in the formation of high molecular weight structures

• : (1) the synthesis of new AB2 monomers without the use of protective groups and with minimal purification; (2) the incorporation of these monomers into dendrimeric architectures; and (3) the examination of how effectively these new dendrimers remove a representative organic pollutant from an aqueous

• obtained when 1 was replaced with methyl 3,5-diaminobenzoate. The single-pot process of preparing derivatized bisimine and bisamine products from 3,5-diaminobenzoic acid (1) and benzaldehyde derivatives eliminates the use of protective groups, removes the need for purification, and follows the general

Efficient synthesis of phenylene-ethynylene rods and their use as rigid spacers in divalent inhibitors

• Francesca Pertici,
• Norbert Varga,
• Arnoud van Duijn,
• Matias Rey-Carrizo,
• Anna Bernardi and
• Roland J. Pieters

Beilstein J. Org. Chem. 2013, 9, 215–222, doi:10.3762/bjoc.9.25

• was used as a side chain, which terminated as a free hydroxy group for 1 and a methoxy group for 2. Silyl groups were used as selective protective groups for the alkyne moiety. Monoalkyne 3 and bisalkyne 4 were made from 1 [29] by a Sonogashira reaction with TIPS-acetylene in 31% and 50%, respectively

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• necessitates aqueous solutions to perform Staudinger reductions in the placement of amino groups as well as for ester saponification used to remove temporary protective groups prior to sulfation. A range of different glycosylation conditions were explored, whereby the couplings were performed either twice by

Asymmetric synthesis of γ-chloro-α,β-diamino- and β,γ-aziridino-α-aminoacylpyrrolidines and -piperidines via stereoselective Mannich-type additions of N-(diphenylmethylene)glycinamides across α-chloro-N-sulfinylimines

• Gert Callebaut,
• Sven Mangelinckx,
• Pieter Van der Veken,
• Karl W. Törnroos,
• Koen Augustyns and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2012, 8, 2124–2131, doi:10.3762/bjoc.8.239

• -aziridino-α-aminocarboxylamides 8 as building blocks in biomedicinal chemistry, some attempts were made to remove the N-protective groups of diaminocarboxylamides 8 under mild acidic conditions (Scheme 4). In analogy with our recently published results on the corresponding aziridino esters [20], amide 8b

Acylsulfonamide safety-catch linker: promise and limitations for solid–phase oligosaccharide synthesis

• Jian Yin,
• Steffen Eller,
• Mayeul Collot and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 2067–2071, doi:10.3762/bjoc.8.232

• Abstract Safety-catch linkers are useful for solid-phase oligosaccharide synthesis as they are orthogonal to many common protective groups. A new acylsulfonamide safety-catch linker was designed, synthesized and employed during glycosylations using an automated carbohydrate synthesizer. The analysis of the

• features of linker 1, the amino–ester bifunctional linker, and linker 2, the safety-catch linker, to create a connection to the solid support that remains stable under conditions for cleaving temporary ester protective groups. Furthermore, the safety-catch linker should enable a variety of different

Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones

• Chunhui Jiang,
• Fangrui Zhong and
• Yixin Lu

Beilstein J. Org. Chem. 2012, 8, 1279–1283, doi:10.3762/bjoc.8.144

• sulfonyl protective groups affected the enantioselectivity. While the employment of nosylimine 1b led to decreased enantioselectivity (Table 1, entry 11), replacement of tosylimine 1a with N-(p-methoxybenzenesulfonyl)imine 1c resulted in further improvement, and the product was obtained in 65% ee (Table 1

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• (1.2 equiv), PPh3 (1.2 equiv), Et3N (1.1 equiv), CH2Cl2, rt, overnight; (g) HCl (1 M) in MeOH, rt, 3 d. Selected reaction conditions of nitrone 1a with lithiated methoxyallene. Acid-induced cleavages of N- and O-protective groups of 5-hydroxy-1,2-oxazine derivatives 6–11; conditions: (a) HCl (1 M) in

Acceptor-influenced and donor-tuned base-promoted glycosylation

• Stephan Boettcher,
• Martin Matwiejuk and
• Joachim Thiem

Beilstein J. Org. Chem. 2012, 8, 413–420, doi:10.3762/bjoc.8.46

• analyze the key principles of oxyanion reactivities. In this work, extended studies on base-promoted glycosylation are presented by using benzyl protective groups in view of preparative applications. Emphases are placed on the influence of the acceptor anomeric configuration and donor reactivities

Multicomponent synthesis of artificial nucleases and their RNase and DNase activity

• Anton V. Gulevich,
• Lyudmila S. Koroleva,
• Olga V. Morozova,
• Valentina N. Bakhvalova,
• Vladimir N. Silnikov and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2011, 7, 1135–1140, doi:10.3762/bjoc.7.131

• or 12 carbon atoms by the standard formylation–dehydration protocol (Scheme 2). We found that these diisocyanides 3 participate successfully in the catalytic three-component reaction via a modified List procedure [25]. Diamides 4 with benzyl protective groups were synthesized in moderate to good

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• (oxazolidine, cyclic ketal, etc.), or deactivated by conversion into amide or carbamate functions. Due to these protective groups even metathesis catalysts sensitive to functionalities can act efficiently under reaction conditions where an adequate balance between activity/stability factors has been met. In

• ring closure (89%) under milder conditions (CH2Cl2): all attempts to employ the 1st-generation Grubbs catalyst 2 in RCM failed, supposedly because of an unfavourable steric environment during generation of the Ru–carbene species from 109, as compared to 98 (distinct N-protective groups). Cyclic sulfate

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• benzoate and TBS-protective groups under the gold-catalyzed conditions had been demonstrated, it was decided to see if (methoxymethyl)oxy substitution has a beneficial impact on the cyclization reactions. In the event, when γ-allenols 12 were treated with AuCl3 the 2,5-dihydrofurans 13 were the sole

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

• chain protective groups was achieved upon treatment with a mixture of TFA, triisopropylsilane and water. The resulting partially deblocked glycopeptide 7 was isolated after purification by semi-preparative RP-HPLC in a yield of 36%, based on the loaded resin 5. The final de-O-acetylation of the glycan

Bis(oxazolines) based on glycopyranosides – steric, configurational and conformational influences on stereoselectivity

• Tobias Minuth and
• Mike M. K. Boysen

Beilstein J. Org. Chem. 2010, 6, No. 23, doi:10.3762/bjoc.6.23

• have introduced new glucosamine-derived bis(oxazolines) 2a–c with uniform protective groups on all oxygen functions [19][20][21] and derivatives 3a–f with cyclic 4,6-O-benzylidene protection as well as various other 3-O-substituents that differ in steric demand and electronic nature [20][21]. These

Synthesis of mesogenic phthalocyanine-C₆₀ donor–acceptor dyads designed for molecular heterojunction photovoltaic devices

• Yves Henri Geerts,
• Olivier Debever,
• Claire Amato and
• Sergey Sergeyev

Beilstein J. Org. Chem. 2009, 5, No. 49, doi:10.3762/bjoc.5.49

• (MEMCl) in the presence of i-Pr2EtN as a base. The general choice of acetal as a protective group was dictated by its excellent stability in the presence of the strong bases, required for the cyclotetramerization of phthalonitriles. Among various popular acetal protective groups, the relatively polar MEM

2-Phenyl- tetrahydropyrimidine- 4(1H)-ones – cyclic benzaldehyde aminals as precursors for functionalised β²-amino acids

• Markus Nahrwold,
• Arvydas Stončius,
• Anna Penner,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2009, 5, No. 43, doi:10.3762/bjoc.5.43

• , this structural modification would facilitate a final release of the β2-amino acid by hydrogenolysis of all remaining benzyl-type N-protective groups. Results and Discussion Cyclocondensation of benzaldehyde and β-amino acid amides to 2-phenyl-tetrahydropyrimidine-4(1H)-ones is problematic, since

• employed in peptide chemistry as asparagine protective groups [52] and as proline mimetics [40]. The class of compounds described in this paper can therefore be considered as a versatile tool in peptide and amino acid chemistry. X-ray crystal structure of 10 [44]. Comparison of coupling constants (C5–C6