Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• . Intermediary diacid was first esterified with diazomethane, then the isopropylidene acetal was hydrolyzed, and diester saponification gave N-Boc-protected compound (2S,3R)-35. Via ketopinic acid functionalized 2(3H)-oxazolones When oxazolone 36 derived from (R)-(−)-ketopinic acid was reacted with bromine and

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• of 53. As reported [30], alkylation of diethyl malonate (4) with 2-(bromomethyl)-1,3-dioxolane (50) gave the diester 51. A controlled saponification led to the mono acid 52 and its reaction with diphenylphosphoryl azide [31][32][33] gave 16% of the target aminoester 53 upon treatment with

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• derivative 134 was realized in the presence of a Pd(OAc)2 catalyst with the aid of the ligand cataCXium A (135) to generate the macrocyclic product 136. Eventually, synthesis of MK-6325 (141) was achieved by adopting saponification followed by amidation (Scheme 20). Conclusion In this review, we have

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• with 6 or 9 gave 11 and 12, again in satisfactory yields (81–85%). Saponification of the ester moiety in 11 and 12 that was formed concomitantly with the O-alkylation in the previous reaction provided Boc-protected modified units B 13 and 14 in 76 and 90% yield, respectively. The synthesis of units C–D

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• final saponification gave the monofluoroalkene-based dipeptide isostere 61. Finally, Fürstner’s group developed the silver-mediated fluorination of functionalized alkenylstannanes to access monofluoroalkenes [42]. Hydrostannation of the N-protected ynamines 62 followed by electrophilic fluorination with

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• epibrassinolide (2) into the corresponding Δ2-steroids. The first route comprised the selective protection of the side chain diol in 1 and 2 through exhaustive acetylation followed by saponification of the intermediate tetraacetates under controlled conditions [14]. Next, a Corey–Winter reaction [15] of the

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• saponification of all ester groups in the presence of isopropanol successfully yielded elansolid B1 (2). When isopropanol was exchanged by methanol, elansolid B2 (3) was generated. Its formation can be rationalized by formation of the intermediate p-methide quinone which selectively trapped methanol, exclusively

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• and carried further saponification of the ester intermediate in another tubular reactor at 90 °C and 1 min residence time. The entire process is carried out at 200 psi pressure and the yield of the target product ibuprofen is reported to be 83%. This report has been among the most eye-popping works in

Interactions between shape-persistent macromolecules as probed by AFM

• Johanna Blass,
• Jessica Brunke,
• Franziska Emmerich,
• Cédric Przybylski,
• Vasil M. Garamus,
• Artem Feoktystov,
• Roland Bennewitz,
• Gerhard Wenz and
• Marcel Albrecht

Beilstein J. Org. Chem. 2017, 13, 938–951, doi:10.3762/bjoc.13.95

• 4 was prepared by Sonogashira reaction of 3 with trimethylsilylacetylene. Subsequent deprotection of the TMS groups using tetra-n-butylammonium fluoride and saponification of the tert-butyl ester with trifluoroacetic acid resulted in the corresponding benzoic acid 6. The latter was coupled to 6

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

• excellent yield (91%). Saponification of all esters in 16 with potassium carbonate followed by acidic cleavage of the isopropylidene acetal group with aqueous acetic acid furnished D-manno-heptulose (1, 76% over two steps). The structure of 1 was found to be in good agreement with those reported for α-D

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• steps from known galactosylazide selenide 23 [29]. Acetylation of the C3 hydroxy group of 23 furnished fully differentially protected selenoglycoside 24 in 82% yield. Hydrolysis of the selenoglycoside using NIS in aqueous THF produced hemiacetal 25 that was silylated prior to selective saponification of

• % yield; it is important to note that Zn-mediated reduction of 51 led to decomposition of the substrate. Ester saponification of 52 employing sodium methoxide in methanol yielded none of the desired product 53 but rather the tentatively assigned β-elimination products 54 and 55. Furthermore, an attempt at

• /toluene (3:1), −10 °C to 0 °C, 54%. Global deprotection to furnish S. pneumonia serotype 12F repeating unit hexasaccharide 1. Reagents and conditions: (a) thioacetic acid, pyridine, rt, 65%; (b) Zn, AcOH/Ac2O/THF, Cu2SO4 (aq, decomposed); saponification conditions that lead to β-elimination (c) i. NaOMe

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

• ). Saponification of the ester of 88 and coupling with H-Ser(Bn)-O-Allyl and treatment with HCl afforded dipeptide 89. A second peptide coupling with acid 90 then gave tripeptide 78. With tripeptide 78 in hand, ligation with the remaining tripeptide 71 followed by cyclisation and global deprotection afforded the

• synthesis reported by Doi et al. [33] to prepare N,O-acetonide 88. N-Mannosylation of acetonide 88 was successful and afforded the desired product in 86% yield (Scheme 19). Saponification then provided the desired benzyl protected mannosyl D-β-hydroxyenduracididine 97. Attempts to utilise the same procedure

Experimental and theoretical insights in the alkene–arene intramolecular π-stacking interaction

• Valeria Corne,
• Ariel M. Sarotti,
• Carmen Ramirez de Arellano,
• Rolando A. Spanevello and
• Alejandra G. Suárez

Beilstein J. Org. Chem. 2016, 12, 1616–1623, doi:10.3762/bjoc.12.158

•  1). Saponification of adducts 11 and 12 provided the free 5-norbornenecarboxylic acid and the chiral auxiliaries 5a and 5b in excellent yields, which can be reused. Conclusion We have reported the synthesis of chiral acrylates derived from renewable feedstock as models to study arene–alkene π

Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates

• Souad Kachbi-Khelfallah,
• Maelle Monteil,
• Margery Cortes-Clerget,
• Evelyne Migianu-Griffoni,
• Jean-Luc Pirat,
• Olivier Gager,
• Julia Deschamp and
• Marc Lecouvey

Beilstein J. Org. Chem. 2016, 12, 1366–1371, doi:10.3762/bjoc.12.130

• 12a,b were obtained in 83% and 81% yield, respectively. The alcohols 12a,b were subsequently firstly deprotonated with NaH in DMF and the generated alcoholates were stirred 16 hours with ethyl bromoacetate giving the expected esters 13a,b in moderate yields. The saponification reactions of the esters

• compounds 1 and 1’a,b. The last step was the saponification of the ethyl ester group. Different usual conditions were tested, leading to partial degradation of the HMBP. The use of a diluted aqueous solution of potassium hydroxide (0.1 M) followed by a protonation with a Dowex® 50WX2 H+ resin allowed us to

Artificial Diels–Alderase based on the transmembrane protein FhuA

• Hassan Osseili,
• Daniel F. Sauer,
• Klaus Beckerle,
• Marcus Arlt,
• Tomoki Himiyama,
• Tino Polen,
• Akira Onoda,
• Ulrich Schwaneberg,
• Takashi Hayashi and
• Jun Okuda

Beilstein J. Org. Chem. 2016, 12, 1314–1321, doi:10.3762/bjoc.12.124

• = 6301 Da). The signal of m/z = 6111 Da results from saponification of the ester and the maleimide moiety (calcd (M + H2O + Na+): m/z = 6111 Da, found: m/z = 6111 Da). We were unable to detect the copper ion in the MALDI–TOF–MS. The isolated biohybrid catalysts were tested in the Diels–Alder reaction of

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• followed by an azide reduction, Boc protection, saponification of the ester, peptide coupling with the amino acid 17, oxidative cleavage of the double bond to give 18 and an intramolecular reductive amination in order to construct the seven-membered ring. Methylation with subsequent acidic global

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• of ethyl (phenylsulfonyl)acetate, a methylsulfonyl anion equivalent, to cyclobutene ester 49 followed by a sequence consisting of saponification, regioselective decarboxylation and reesterification to afford methyl ester 50. The ester group was reduced with lithium aluminum hydride and the resulting

• aldehyde 67 in six steps in 34% yield. After saponification of the ester functionality, treatment with tosyl chloride and trimethylamine resulted in the formation of a ketene that underwent a diastereoselective intramolecular [2 + 2] cycloaddition to provide bicyclic ketone 69. Addition of TMS cerium

Asymmetric 1,4-bis(ethynyl)bicyclo[2.2.2]octane rotators via monocarbinol functionalization. Ready access to polyrotors

• Cyprien Lemouchi and
• Patrick Batail

Beilstein J. Org. Chem. 2015, 11, 1881–1885, doi:10.3762/bjoc.11.202

• was obtained from 7 by a modified deprotection procedure of the carbinol group using NaH instead of KOH under dry conditions, thereby allowing the deprotection to proceed succesfully while preventing the ester saponification [19][20]. Indeed, keeping the ester function is of primary importance for

• solubility considerations, as it enhances the reactivity in the homocoupling reaction and also facilitates the purification of 9 by chromatography on silica gel. This yielded the dicarboxylate diyne dirotor 10 with the high purity required for the preparation of framework solids. Saponification of the ester

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• -aryl migration step. This was mediated by a hypervalent iodine reagent, PhI(OAc)2 (13), conducted in trimethyl orthoformate (14, TMOF) and methanol (Scheme 2). The direct saponification of the resulting rearranged methyl ester with an excess of base thus completed the telescoped flow synthesis of

• (Friedel–Crafts acylation, 1,2-aryl migration and saponification) this report focuses on improved output by intensifying the overall sequence (Scheme 3). As such an in-line extraction is performed after the Friedel–Crafts acylation step, followed by dissolving intermediate 18 in trimethyl orthoformate and

Carboxylated dithiafulvenes and tetrathiafulvalene vinylogues: synthesis, electronic properties, and complexation with zinc ions

• Yunfei Wang and
• Yuming Zhao

Beilstein J. Org. Chem. 2015, 11, 957–965, doi:10.3762/bjoc.11.107

• . Saponification was then performed on compound 5 in a solution of NaOH in water and methanol to finally afford carboxyl-TTFV 6 in 84% yield. Compound 6 showed relatively poor solubility in non-polar organic solvents, but could be readily dissolved in polar solvents such as MeOH, EtOH, THF, and DMSO. For

Synthesis of tripodal catecholates and their immobilization on zinc oxide nanoparticles

• Franziska Klitsche,
• Julian Ramcke,
• Julia Migenda,
• Andreas Hensel,
• Tobias Vossmeyer,
• Horst Weller,
• Silvia Gross and
• Wolfgang Maison

Beilstein J. Org. Chem. 2015, 11, 678–686, doi:10.3762/bjoc.11.77

• chloride to give acrylamide 4. Treatment of 4 with dimethylamine and excess KOH leads to the nucleophilic addition of the amine and saponification of the methyl esters in one step to give the free acid 5 after acidic work-up. Subsequent coupling of 5 to dopamine acetonide 6 with EDC and HOBt gave the

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• first step histidine methylester hydrochloride (40) is acylated with anthracene-9-acetic acid to give 41. After saponification of the ester the potassium salt of the corresponding acid 42 was treated with 32c affording the articulated rod 43 in quantitative yield (Scheme 10). The stretched–folded

Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• strategies [10]. Results and Discussion Our synthesis of building blocks 1 and 2 started from known 3-azidomethyl-5-nitrobenzoic acid methyl ester 3 which was prepared from commercially available dimethyl 5-nitroisophthalate in 64% overall yield [12][13]. Saponification of the methyl ester in 3 with aqueous

Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• use of compound 6 as nucleobase acceptor improved the yield of nucleosides 7α,β in general and led to an acceptable β:α = 2.5:1 ratio of anomers. Subsequent saponification of 7α,β (unseparable by flash chromatography) proved to be tricky and after testing a series of standard techniques, only