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

• that amino acid chemistry has fostered the development of a number of specialized methodologies to handle the manifold functional groups present in the most common amino acids. A salient example is the copper chelation chemistry originally introduced by Kurtz in 1941 to isolate lysine from protein

• liberating the acylated derivative from its copper salt using 8-hydroxyquinoline as an organic chelating precipitant [8]. While both useful and creative, the copper chelation procedure carries with it many of the same shortcomings as other types of protective group chemistry. However, by a change of the

A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry

• Chrysie Aggelidou,
• Theodossis A. Theodossiou,
• Antonio Ricardo Gonçalves,
• Mariza Lampropoulou and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 2414–2420, doi:10.3762/bjoc.10.251

• cancerous rather than squamous tissues [1]. δ-Aminolevulinic acid (1, ALA, Scheme 1) is a δ-amino acid precursor in the cellular biosynthesis of heme [2]. The penultimate step in this biosynthetic cycle is the iron chelation of protoporphyrin IX (PpIX), a porphyrin photosensitizer (PS) which was shown to be

Efficient CO₂ capture by tertiary amine-functionalized ionic liquids through Li⁺-stabilized zwitterionic adduct formation

• Zhen-Zhen Yang and
• Liang-Nian He

Beilstein J. Org. Chem. 2014, 10, 1959–1966, doi:10.3762/bjoc.10.204

• cations derived from chelation between neutral ligands and Li+ are shown in Figure 1. The geometry optimizations were carried out by performing DFT calculations. Four O atoms in PEG150Me chelate with Li+ in a quasi-crown ether manner. For neutral ligands with PEG chain (PEG150MeIm, PEG150MeNH2

• cycles. Typical optimized structures of complex cations derived from chelation between Li+ and neutral ligands. H: white, C: grey, O: red, N: blue, Li: purple. Bond lengths are in Å. (a) Comparison of the thermal stability between the neutral ligands and the corresponding chelated ionic liquids after

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• bonds, which can isomerize more readily than secondary amides, and to the absence of amide protons, which stabilize secondary structure by backbone hydrogen bonding [15][16]. As we have previousy demonstrated, this heterogeneity can be reduced by metal chelation [35][38]. Addition of an excess of sodium

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• -histidinyl acetyl (NαHis-ac) chelator (Figure 5) was attached to lysine side chains or the N-terminus of the peptide by manual coupling, whereas the chelation with 99mTc occurred in solution [133]. The incorporation of carbaboranes that can be used for boron neutron capture therapy demonstrated the potential

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• chiral phosphine ligands and AgOAc via bidentate chelation of a properly substituted aldimine. Chiral phosphine–silver(I) complexes are emerging as a valuable tool for carbon–carbon bond forming reactions. These catalysts are effective in promoting enantioselective allylations, aldol reactions, Mannich

• bidentate chelation (Scheme 36). The substrate is bound anti to the bulky amino acid substituent (R) and reacts with the siloxyfuran via endo-type addition. Intramolecular silyl transfer, iPrOH mediated desilylation of the amide terminus, and protonation of the N–Ag bond delivers the final product and the

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• . Depending on the stereofacial selectivity, one can access either the anti-isomer 12 or syn-isomer 13 as the major product (Scheme 7). The high anti-selectivity can be rationalized with the attack of the nucleophile from the sterically least hindered side (re-side attack). The Felkin–Anh non-chelation

• density from the reaction center toward nitrogen. In cases where syn-selectivity is observed, the Cram’s chelation control model provides an explanation [56][57]. Chelating metal coordinates between the two carbonyls (the aldehyde and the carbamate), thus forcing the nucleophile to attack from the si-side

• syn-selectivities were achieved with vinylZnCl in Et2O (1:6 anti/syn). Coleman also noticed that the addition of excess ZnCl2 did not increase the syn-selectivity at all. They attributed this to the mono-coordination of the metal to the carbamate instead of the usual “bidentate” chelation control

Regioselective carbon–carbon bond formation of 5,5,5-trifluoro-1-phenylpent-3-en-1-yne

• Motoki Naka,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2013, 9, 2182–2188, doi:10.3762/bjoc.9.256

• electrophiles, under equilibration of the possible two anionic species. Keywords: additives; computation; Li···F chelation; deprotonation; electron-withdrawing effect; organo-fluorine; Introduction We have previously reported [1] the interesting behavior of (E)-1-chloro-3,3,3-trifluoropropene ((E)-1) [2][3][4

• initial Hb abstraction from (E)-1 and the resultant Int-1 was stabilized by the energetically favorable 5-membered intramolecular Li···F chelation [5]. This intermediate Int-1 experienced Fritsch–Buttenberg-Wiechell (FBW) rearrangement [6][7] to give 3,3,3-trifluoropropyne, and Int-2 derived from this

• ] of the trans-disposed chlorine atom. However, it is also likely that the anionic intermediate produced after Hb abstraction would prefer the reaction course to 2 by way of FBW rearrangement because of its lower stability than Int-1 with loss of the possibility for Li···F chelation. It was not only

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• ) was carried out (Scheme 5). The aldehyde (R)-2, which was prepared from D-serine [42][43][44], underwent chelation-controlled nucleophilic addition of metallated alkyne 3 [45] to give the propargyl alcohol 14 in 84% yield and a syn-diastereoselectivity of >95:5 [7][46][47]. After tosylation of 14 (85

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• most likely candidate for chelation is the oxygen protected as the PMB ether. Although an eight-membered chelate might seem too large to play an important role in directing regioselectivity, the 3:1 regioselectivity observed in the “normal” direction is consistent with chelation playing a diminished

Diastereoselective radical addition to γ-alkyl-α-methylene-γ-butyrolactams and the synthesis of a chiral pyroglutamic acid derivative

• Tomoko Yajima,
• Eriko Yoshida and
• Masako Hamano

Beilstein J. Org. Chem. 2013, 9, 1432–1436, doi:10.3762/bjoc.9.161

• the reaction were also revealed. This stereoselective radical reaction was used for synthesis of chiral pyroglutamic acid derivatives starting from a commercially available chiral amino acid. Keywords: chelation controlled reaction; diastereoselective reaction; free radical; lactams; pyroglutamic

• -selectivities were not observed for substrates with pivaloyl groups, and it appears that steric hindrance between the pivaloyl group and the lactam γ-alkyl disturbs chelation. Using the acetyl group, which is less sterically hindered than the pivaloyl group, improved the chelate formation of γ-isobutyl or γ

• -substituent on the substrate. The reactions using N-acetyl substrates instead of pivaloyl substrates yielded better trans-selectivities with γ-isobutyl and γ-phenethyl substrates, because acetyl is sufficiently small to allow chelation with the Lewis acid and lactam carbonyl. We used the reaction to

Cascade radical reaction of substrates with a carbon–carbon triple bond as a radical acceptor

• Hideto Miyabe,
• Ryuta Asada and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2013, 9, 1148–1155, doi:10.3762/bjoc.9.128

• solvent MeOH gave the nearly racemic product, although the high Z-selectivity was maintained (Table 1, entry 10). These results suggest that the rigid chelation of the chiral Lewis acid to the hydroxamate ester functionality occured in CH2Cl2. In the presence of chiral Lewis acid, hydroxamate ester 6C had

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• good pharmacokinetic profile of 124 warrants further investigation in vivo. [Re] and [99mTc]-labeled benzofurans, BAT-Bp-2 (125a,b), were synthesized from 132 by reductive monoamination and O-demethylation to give 135 (Scheme 9D) [88]. Subsequent reaction with the protected chelation ligand TRT-Boc-BAT

Regio- and stereoselective carbometallation reactions of N-alkynylamides and sulfonamides

• Yury Minko,
• Morgane Pasco,
• Helena Chechik and
• Ilan Marek

Beilstein J. Org. Chem. 2013, 9, 526–532, doi:10.3762/bjoc.9.57

• give 3c (Table 1, entry 3). Although N-heterosubstituted alkynes were used in all cases, the α-isomer is regioselectively obtained, as confirmed by 1H NMR analysis of the crude reaction mixture after hydrolysis, through an intramolecular chelation between the N-sulfonamide moiety and the organocopper

• species. To improve the chemical yield of this transformation, we considered the copper-catalyzed carbomagnesiation reaction. However, such catalytic reaction requires a transmetallation reaction of the intermediate vinylcopper into vinylmagnesium halide, and due to the intramolecular chelation, it is

• -regioisomer, albeit in moderate yield. On the other hand, in the presence of the 1-adamantylester substituted substrate 7d, the two α/β-isomers were formed in a 8:2 ratio (Table 3, entry 8). This loss of selectivity may be explained either by a competitive chelation of the carbonyl group of the ester

De novo synthesis of D- and L-fucosamine containing disaccharides

• Daniele Leonori and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 332–341, doi:10.3762/bjoc.9.38

• are usually further elongated at the C3 position in P. aeruginosa requiring two orthogonal protecting groups (PGs) at C3 and C4 of the building block in order to differentiate the two hydroxy groups at a later stage. The three carbon C4–C6 fragment of D-fucosamine was introduced by chelation

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• chiral ligand required to provide high enantiofacial selectivity for a broader range of substrates are still unclear. The intermolecular reactions usually take advantage of chelation and stabilizing effects on the resulting organolithium to obtain high enantioselectivity and avoid polymerization

One-pot tandem cyclization of enantiopure asymmetric cis-2,5-disubstituted pyrrolidines: Facile access to chiral 10-heteroazatriquinanes

• Ping-An Wang,
• Sheng-Yong Zhang and
• Henri B. Kagan

Beilstein J. Org. Chem. 2013, 9, 265–269, doi:10.3762/bjoc.9.32

• substance class in organic chemistry containing nitrogen and three fused five-membered rings [1][2][3]. Due to the unique rigid bowl-shaped structure with one noninversible electron lone pair at the bottom of the central nitrogen (“centro-N”) atom, 10-azatriquinane analogues are used as efficient chelation

Alternaric acid: formal synthesis and related studies

• Michael C. Slade and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2013, 9, 166–172, doi:10.3762/bjoc.9.19

• glyoxylate 1a under previously optimized conditions, high efficiency was achieved along with excellent (>20:1) stereochemical control for the formation of three-component-coupling product 17 (Scheme 7) [41][42][43][44]. To verify that the dithiane was acting in the desired fashion, and to rule out chelation

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• TcCYP51. For 4, the ligand, the protein, and the heme group are shown in green, pink, and grey, respectively. For (R)-5, the ligand, the protein, and the heme group are shown in cyan, purple, and white, respectively. Heme-iron chelation and hydrophobic binding interactions dominate in the models. (B

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• , which can dramatically affect both the regio- and stereochemical outcomes due to the polarization of the triple bond and/or the formation of chelation-stabilized vinylmetal species. The carbometallation of O-, N-, P-, S-, and Si-substituted alkynes has indeed been quite extensively studied and shown to

• assumptions: According to the remarkable work of the Beak group on the α-lithiation of Boc-protected amines [34][35][36][37][38], N-allyl-ynamides 1 should be readily deprotonated to afford a transient chelation-stabilized allyllithium 2 and, provided that a metallotropic equilibrium exists between this

• intermediate and the less-stable allyllithium 3, an intramolecular carbometallation may then occur to yield a chelation-stabilized vinyllithium 4 and drive the overall process to the formation of the heterocyclic ring system. Further reaction with an electrophile followed by aqueous workup or hydrolysis under

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

• are minimized and Li-chelation stabilizes the conformation (Scheme 3), regardless of the base that was used [30][31]. Reaction of the Z-enolates via a cyclic chelated six-membered chairlike transition-state model TS-6a, would have resulted in anti-addition products anti-5 in analogy with our

• the glycinamides 4, as compared to the reaction with glycine esters, is attributed to the α-coordinating ability of the chlorine atom with the lithium of the incoming enolate as depicted in transition state TS-6b. The coordinating α-chloro atom in TS-6b overrides the chelation of the sulfinyl oxygen

Design and synthesis of quasi-diastereomeric molecules with unchanging central, regenerating axial and switchable helical chirality via cleavage and formation of Ni(II)–O and Ni(II)–N coordination bonds

• Vadim A. Soloshonok,
• José Luis Aceña,
• Hisanori Ueki and
• Jianlin Han

Beilstein J. Org. Chem. 2012, 8, 1920–1928, doi:10.3762/bjoc.8.223

• difference between the designed quasi-diastereomers 5 and 6 is that the noncoordinated arm CDE and the substituent R on the stereogenic coordination site C in 5 are on the same side of the metal chelation plane, while in structure of 6 the arm CBA and the substituent R are on the opposite sides. In contrast

• . Initial assignment of the structures of compounds 19/20 by NMR was not possible because of the very fast exchange between Ni–O=C and Ni–NH=C chelation. Thus, due to fast interconversion between compounds 19 and 20, only broad signals were observed in the 1H NMR spectra recorded at ambient temperature

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• moderate to good yield (Scheme 6). A mechanism including an electrophilic palladation involving the pyridinyl chelation was thought to be plausible taking into account the outcome of the reaction performed on isotopically labeled substrates as well as by kinetic studies of variously substituted indoles

A simple and efficient dual optical signaling chemodosimeter for toxic Hg(II)

• Sabir H. Mashraqui,
• Sapna A. Tripathi,
• Sushil S. Ghorpade and
• Smita R. Britto

Beilstein J. Org. Chem. 2012, 8, 1352–1357, doi:10.3762/bjoc.8.155

• presently conceived the design of simple and easily accessible 10-methylthioacridone – designated as acrithion 2 – as a new chemodosimeter for the highly selective colorimetric and fluorescence signaling of Hg2+. The chemodosimeter mechanism, illustrated in Scheme 1, is proposed to proceed via chelation of

On the proposed structures and stereocontrolled synthesis of the cephalosporolides

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2012, 8, 1287–1292, doi:10.3762/bjoc.8.146

• Sami F. Tlais Gregory B. Dudley Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390 USA, Fax: (850) 644-8281 10.3762/bjoc.8.146 Abstract The synthesis of four candidate stereoisomers of cephalosporolide H is described, made possible by a zinc-chelation

• strategy for controlling the stereochemistry of oxygenated 5,5-spiroketals. The same strategy likewise enables the first stereocontrolled synthesis of cephalosporolide E, which is typically isolated and prepared admixed with its spiroketal epimer, cephalosporolide F. Keywords: cephalosporolides; chelation

• structures of cephalosporolide E and F. Results and Discussion We recently reported the stereocontrolled synthesis of cephalosporolide H (reported structure) and its spiroketal isomer [32]. Our strategy featured the use of zinc salts to control the spiro-center using either steric biases or chelation