Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

• Patrick Rabe,
• Tim A. Klapschinski,
• Nelson L. Brock,
• Christian A. Citron,
• Paul D’Alvise,
• Lone Gram and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2014, 10, 1796–1801, doi:10.3762/bjoc.10.188

• efficiently converted into 13 by stirring in TFA. The synthesis of 12a followed a previously published route for ethyl tropone-2-carboxylate (12b) [14], but saponification of this ester led to decomposition, and therefore, the tert-butyl ester 12a was prepared that allowed for a conversion into 13 under

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• into neryl acetate ((Z)-19) in 87%, followed by allylic oxidation [38], to provide enal (Z)-20 and allylic alcohol (Z)-21 in 14% and 41% yield, respectively. Saponification of 8-hydroxyneryl acetate ((Z)-21) under the above mentioned conditions gave 8-hydroxynerol (4) in 73% yield (Scheme 2). Following

Synthesis of zearalenone-16-β,D-glucoside and zearalenone-16-sulfate: A tale of protecting resorcylic acid lactones for regiocontrolled conjugation

• Hannes Mikula,
• Julia Weber,
• Dennis Svatunek,
• Philipp Skrinjar,
• Gerhard Adam,
• Rudolf Krska,
• Christian Hametner and
• Johannes Fröhlich

Beilstein J. Org. Chem. 2014, 10, 1129–1134, doi:10.3762/bjoc.10.112

• dry DMF after optimization in terms of base and solvent type (Scheme 4A). Königs–Knorr glucosylation of the PMB-protected mimic 15 afforded 16, which was deprotected using 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) for oxidative PMB cleavage and subsequent ester saponification to yield the desired

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• nucleophile preferentially attacks from the re-face as shown in TS 1 (Figure 4) to give 10b [48][55]. In the next step, ester saponification of 10a using lithium hydroxide afforded D-glucose derived β-amino acid 11a in 84% yield. Finally, N-terminal fluorenylmethoxycarbonyl (Fmoc) protection of the β-amino

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• conditions. As the presence of a methyl ester would prevent the selective introduction of one thioester into 5a by saponification–thioesterification, we planned transesterification from a suitably activated carboxylic acid derivative 8. Alternatively, direct introduction into 11 with appropriate SNAc

• assay mixture, the latter will be transformed into their corresponding methyl esters by saponification and following methylation with trimethylsilyldiazomethane. The fully protected E-isomer 10a was obtained in 18% yield by a Horner–Wadsworth–Emmons reaction with phosphonate 25 or, alternatively, in 64

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• -cyclohexylglycine methyl ester pyrazinecarboxylic acid followed by a saponification afforded the carboxylic acid 62. Moreover, for the isocyanide component, the Dess–Martin oxidation of 60 and the subsequent Passerini reaction could be performed in one-pot, since the former reaction produces acetic acid as

• , thioacetic acid and 4-methoxy-phenylethylamine (also as chiral auxiliary) provided the corresponding Ugi product 138 in 60% yield (dr 1:1). Chiral separation and deprotection in TFA resulted in compound 139 in 70% yield, after which saponification followed by an amide coupling with tryptamine and CDI

Self-assembly of metallosupramolecular rhombi from chiral concave 9,9’-spirobifluorene-derived bis(pyridine) ligands

• Rainer Hovorka,
• Sophie Hytteballe,
• Torsten Piehler,
• Georg Meyer-Eppler,
• Filip Topić,
• Kari Rissanen,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 432–441, doi:10.3762/bjoc.10.40

• subjected to an acid-mediated condensation to give the 9,9’-spirobifluorene. Friedel–Crafts acylation with acetyl chloride gave rise to the racemic 2,2’-diketone which was transformed to the racemic diester in a Baeyer–Villiger oxidation. Saponification of the ester functions then afforded (rac)-1. One part

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• of the NK-1 inhibitor L-733,060 in 8 steps. Additionally, a cyclodehydration-realizing simple triethylphosphite as a substitute for triphenylphosphine is developed. Here the stoichiometric oxidized P(V)-byproduct (triethylphosphate) is easily removed during the work up through saponification

• (of O=P(OiPr)3). In our case we were not able to remove stoichiometric amounts of OP(OEt)3 (which is more hydrophilic than OP(OiPr)3) through an aqueous work up (without saponification). Moreover, pentavalent P(OEt)5 prepared from P(OEt)3 with diethylperoxide and ethylbenzenesulfonate, respectively

• Schotten–Baumann conditions [62][63]. Thus, K2CO3 (→ pH = 10) as the base prevented saponification of the side chain methyl ester functions (as observed with hydroxide salts). Nevertheless, in the acylation of the glutamic acid derivative 8e the corresponding pyroglutamic acid derivative 2g resulting from

Convergent synthesis of a tetrasaccharide repeating unit of the O-specific polysaccharide from the cell wall lipopolysaccharide of Azospirillum brasilense strain Sp7

• Pintu Kumar Mandal,
• Debashis Dhara and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2014, 10, 293–299, doi:10.3762/bjoc.10.26

• transformed to the target compound 1 in an overall 69% yield following a sequence of reactions consisting of (a) the conversion of the N-phthaloyl group to an acetamido group [41], (b) the hydrogenolysis with hydrogen over Pearlman’s catalyst [42], and (c) the saponification with sodium methoxide. A NMR

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• . The resulting major alcohol was protected, followed by saponification of the ester with concomitant removal of the TBDPS-protecting group. The resulting free alcohol was then re-protected to give bicycle 40. Barton decarboxylation was then achieved using standard conditions, followed by trapping of

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

Gold-catalyzed glycosidation for the synthesis of trisaccharides by applying the armed–disarmed strategy

• Abhijeet K. Kayastha and
• Srinivas Hotha

Beilstein J. Org. Chem. 2013, 9, 2147–2155, doi:10.3762/bjoc.9.252

• . Subsequently, the disarmed disaccharide 3 was transformed into an armed glycosyl donor 4 by simple saponification followed by etherification. The reaction between armed donor 4 and disarmed aglycon 2, which was carried out under the aforementioned conditions did not result in the formation of desired

• allowed to react with disarmed aglycon 22 in the presence of AuCl3 (5 mol %)/AgSbF6 (5 mol %) in CH3CN/CH2Cl2 (1:1) at 25 °C for 4 h to obtain the disarmed disaccharide 23 in 85% yield. Further, the armed disaccharide 24 was synthesized from 23 by saponification followed by the etherification in 84% over

Synthesis of mucin-type O-glycan probes as aminopropyl glycosides

• David Benito-Alifonso,
• Rachel A. Jones,
• Anh-Tuan Tran,
• Hannah Woodward,
• Nichola Smith and
• M. Carmen Galan

Beilstein J. Org. Chem. 2013, 9, 1867–1872, doi:10.3762/bjoc.9.218

• sialylated 22b, as the ester groups were removed by reaction with sodium methoxide in methanol followed by saponification of the methyl ester with LiOH at room temperature and subsequent azide reduction catalysed by hydrogen and Pd/C in water to give target 6 in 80% overall yield (Scheme 2). The presence of

A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• 2-hydroxy compound 31 as a single diastereoisomer (as determined by 1H NMR) in 71% yield. Esterification with MeOMgCl [69] (which has been shown not to cause epimerization at the α-position [67]) and saponification [70] afforded (S)-2-hydroxy-15-methylpalmitic acid (32). The ketone 33 was isolated

Straightforward synthesis of a tetrasaccharide repeating unit corresponding to the O-antigen of Escherichia coli O16

• Manas Jana and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 1757–1762, doi:10.3762/bjoc.9.203

• transfer hydrogenation with triethylsilane and 10% Pd/C [20]; (b) an acetylation using acetic anhydride and pyridine, and (c) a saponification reaction with sodium methoxide to furnish compound 1, which was purified over a Sephadex® LH-20 gel to give the pure compound 1 in 64% overall yield. The structure

Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step

• James C. Anderson,
• Andreas S. Kalogirou,
• Michael J. Porter and
• Graham J. Tizzard

Beilstein J. Org. Chem. 2013, 9, 1737–1744, doi:10.3762/bjoc.9.200

• allow elucidation of the absolute stereochemistry of piperazirum (2). Results and Discussion The common α-keto acid derivative 5 was easily prepared from a Grignard reaction of isobutylmagnesium chloride with diethyl oxalate to give α-keto ester 10 in 94% yield (Scheme 3) [47]. Saponification of 10 with

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

• . [Re] and [99mTc]BAT-BTA (84a and 84b; note: BAT = bis(aminoethanethiol)) were prepared by addition of ethyl bromoacetate (41) to the unprotected amine of the S,S'-bis-trityl-N-Boc-1,2-ethylenedicysteamine chelating agent (90) followed by saponification that gave the free acid intermediate 91, which

Study on the total synthesis of velbanamine: Chemoselective dioxygenation of alkenes with PIFA via a stop-and-flow strategy

• Huili Liu,
• Kuan Zheng,
• Xiang Lu,
• Xiaoxia Wang and
• Ran Hong

Beilstein J. Org. Chem. 2013, 9, 983–990, doi:10.3762/bjoc.9.113

• where iodolactones, obtained from the iodolactonization of alkenes in the presence of iodine, can be converted into hydroxylactone upon saponification [40][41]. This appealing metal-free protocol evolved into enantioselective iodolactonization by using chiral amides or esters. The catalytic asymmetric

Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway

• Jessica L. Bell,
• Andrew J. Haak,
• Susan M. Wade,
• Yihan Sun,
• Richard R. Neubig and
• Scott D. Larsen

Beilstein J. Org. Chem. 2013, 9, 966–973, doi:10.3762/bjoc.9.111

• -benzoylbenzoic acid afforded the final probe 19. Synthesis of a photoprobe based on the most active model 8c is shown in Scheme 4. Acid 20 was esterified prior to alkylation with propargyl bromide, affording ester 22. Saponification, followed by amidation with the previously prepared piperidine 6c, provided the

Short synthesis of the common trisaccharide core of kankanose and kankanoside isolated from Cistanche tubulosa

• Goutam Guchhait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 705–709, doi:10.3762/bjoc.9.80

• the presence of borontrifluoride diethyl etherate furnished 2-phenylethyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside (2) in 84% yield [10]. Saponification of compound 2 by using 0.1 M sodium methoxide in methanol followed by benzylidene acetal formation by using benzaldehyde dimethylacetal in the

• δ 100.8 (C-1A), 100.5 (C-1C), 98.8 (C-1B) in the 13C NMR spectra]. Saponification of compound 8 by using 0.1 M sodium methoxide in methanol furnished compound 1 in 94% yield. Spectral analysis of compound 1 unambiguously confirmed its formation [signals at δ 5.16 (br s, H-1B), 4.37 (d, J = 7.5 Hz, H

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

• in 61% yield over two steps (β anomer, 3JH1–H2 of 7.8 Hz, Scheme 6A). Global deprotection employed saponification, and hydrogenation gave the fully deprotected D-fucosamine containing disaccharide 17 (Scheme 6A). When the same synthetic sequence was performed on L-FucNAc building block L-10 the fully

Presence or absence of a novel charge-transfer complex in the base-catalyzed hydrolysis of N-ethylbenzamide or ethyl benzoate

• Shinichi Yamabe,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2013, 9, 185–196, doi:10.3762/bjoc.9.22

• dilute alkali is the usual way of hydrolyzing esters, and the reaction is called saponification. The base-catalyzed hydrolysis of amides is an important model for the enzymatic cleavage of peptide bonds [2][3]. The base-promoted hydrolyses of carboxylic esters and amides accompanying the 18O exchange

• tetrahedral intermediate is formed by direct nucleophilic collisions between hydroxide ions and ester molecules. Marlier's suggestion was supported by a kinetic study of the saponification of ethyl acetate (CH3COOC2H5) [20]. For the base-catalyzed amide hydrolysis, Brown and co-workers made extensive studies

• ][28][29][30][31][32][33][34][35][36][37]. As stated in [20], "an appropriate mechanistic picture for the system (saponification) must take into account the solvent molecules that should be included in the minimal TS structure". The mechanisms of the well-known two base-catalyzed hydrolyses are still

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

• ] to afford intermediate 11 and removal of the Boc protecting group furnished amine 12. Condensation of 7 and 12 provided precursor 13 in 63% yield. Finally, linker 1 was obtained by saponification of methyl ester 13. In the next step, solution-phase studies towards cleavage of linker 1 from a solid

• 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

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• investigated and resulted in increased formation of side products [11]. After saponification of intermediate 5 to dipeptide 6, the latter was coupled with benzyl anthranilate. This reaction was particularly challenging due to the very poor reactivity of this combination [10]. All attempts to perform this

• conditions followed by saponification afforded the desired carboxylic acid 3 in 21% yield over the two steps (Scheme 3). The MCR approach to building block 3 with two convertible components gives lower yields compared to the classical amide formation, but it carries the diversity-generating ability inherent

• , with imine preformation in methanol, to give 13a in 51% yield. Finally, saponification of 13a afforded the racemic viridic acid (±)-1 in 83% yield. Attempts to improve the MCR yield with conventional or microwave heating, or by employing trifluoroethanol or DMF as solvents resulted in poor conversions

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

• reaction conditions on solid support since cleavage only occurs following preactivation. Thus, different modification reactions, such as Staudinger reduction, ester saponification or sulfation, necessary for the synthesis of GAGs, can be performed on solid support in an automated carbohydrate synthesizer

• the presence of NEt3 afforded a crude carbonate, which was smoothly reacted with amine 4 to provide carbamate 7 with 85% yield. Carbamate 7 was converted to the free acid 9 by simple protection to form THP ether 8 followed by saponification. Finally, coupling acid 9 with 4-sulfamoylbenzoic acid [15