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

Convergent synthesis of the tetrasaccharide repeating unit of the cell wall lipopolysaccharide of Escherichia coli O40

• Abhijit Sau and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2012, 8, 2053–2059, doi:10.3762/bjoc.8.230

• compound 7 was confirmed from its spectral analysis [signals at δ 4.73 (d, J = 8.0 Hz, H-1B), 4.41 (br s, H-1A) in the 1H NMR and at δ 101.6 (C-1A), 100.7 (C-1B) in the 13C NMR spectra respectively]. Saponification of compound 7 by using sodium methoxide followed by 3,4-O-isopropylidenation with 2,2

Automated synthesis of sialylated oligosaccharides

• Davide Esposito,
• Mattan Hurevich,
• Bastien Castagner,
• Cheng-Chung Wang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 1601–1609, doi:10.3762/bjoc.8.183

• with a benzoyl group at the C3 hydroxy position resulted in a lower glycosylation yield (36%), suggesting that an ester can lower the nucleophilicity of the vicinal C4-hydroxy. The synthesis was completed by deacetylation of compound 15 under Zemplén's conditions, followed by saponification and

• were applied to the synthesis of GM3 trisaccharide 16 previously prepared in solution phase (see above). Glucose thioglycoside building block 21 and disaccharide building block 4 served for the assembly of 16 (Scheme 4). Final saponification afforded the partially protected glycan 22 in 40% overall

• optimized conditions, the branched tetrasaccharide 26 was isolated in 51% overall yield after TCA reduction, cleavage, ester saponification and HPLC purification. Finally, solution-phase hydrogenolysis gave tetrasaccharide 27. Automated synthesis of linear α–(2→6) sialosides α-(2→6) Sialylated

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part II: Iridomyrmecins

• Robert Hilgraf,
• Nicole Zimmermann,
• Lutz Lehmann,
• Armin Tröger and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1256–1264, doi:10.3762/bjoc.8.141

• C and D was completed in three additional steps (Scheme 2). The oxidation with Jones reagent yielded 14, and subsequent saponification of the acetate group with methanolic KOH afforded the hydroxy acid 6. Similar to the approach described above, careful lactonization with DCC and DMAP gave

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

• Nicole Zimmermann,
• Robert Hilgraf,
• Lutz Lehmann,
• Daniel Ibarra and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140

• furnish the primary alcohol 31, which upon oxidation will yield the corresponding aldehyde that can be epimerized to the diastereomers 32/32* as shown above. Subsequent reduction of 32/32*, silylation of the resulting primary alcohols and saponification will produce a mixture of the diastereoisomers 33/33

Partial thioamide scan on the lipopeptaibiotic trichogin GA IV. Effects on folding and bioactivity

• Marta De Zotti,
• Barbara Biondi,
• Cristina Peggion,
• Matteo De Poli,
• Haleh Fathi,
• Simona Oancea,
• Claudio Toniolo and
• Fernando Formaggio

Beilstein J. Org. Chem. 2012, 8, 1161–1171, doi:10.3762/bjoc.8.129

• : Deprotection by catalytic hydrogenation with Pd/C. 4: Thionation with Lawesson's reagent in THF. 5: Coupling with n-Oct-OH in the presence of EDC/HOBt. 6: Saponification with NaOH/MeOH. 7: Coupling in the presence of EDC/HOAt. Synthesis of ψ[CS-NH]5. 1: Coupling in the presence of EDC/HOBt. 2: Deprotection by

Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

• Kieron M. G. O’Connell,
• Monica Díaz-Gavilán,
• Warren R. J. D. Galloway and
• David R. Spring

Beilstein J. Org. Chem. 2012, 8, 850–860, doi:10.3762/bjoc.8.95

• EtOH and H2O under reflux to achieve ester saponification, which was followed by decarboxylation, proceeding smoothly to give the corresponding ketone in 76% yield. The ketone was then transformed to the exocyclic alkene 15 in 61% yield by Wittig reaction with the appropriate phosphonium salt. The

Synthesis and antifungal properties of papulacandin derivatives

• Marjolein van der Kaaden,
• Eefjan Breukink and
• Roland J. Pieters

Beilstein J. Org. Chem. 2012, 8, 732–737, doi:10.3762/bjoc.8.82

• synthesis started with the saponification of 15, followed by the protection of O-4 and O-6 by using di-tert-butylsilyl bis(trifluoromethanesulfonate). Subsequent protection of O-3 with TES-Cl, gave the fully protected glucal 18. According to Denmark et al. [31], lithiation and silylation of 18 should give

Synthesis of fluorinated maltose derivatives for monitoring protein interaction by ¹⁹F NMR

• Michaela Braitsch,
• Hanspeter Kählig,
• Georg Kontaxis,
• Michael Fischer,
• Toshinari Kawada,
• Robert Konrat and
• Walther Schmid

Beilstein J. Org. Chem. 2012, 8, 448–455, doi:10.3762/bjoc.8.51

• anomeric acetyl group of compound 2 with hydrazine acetate [29] yielding derivative 7, followed by nucleophilic fluorination with DAST [30][31] generating the diasteriomeric mixture 8. The α-anomer was isolated by HPLC and subsequent Zemplén saponification of the remaining acetate protecting groups yielded

• with Pd/C [36], followed by a Zemplén saponification to obtain product 15. Starting from 4′,6′-O-benzylidene maltose 10 [37], the primary alcohol was protected as tert-butyldimethylsilyl ether followed by standard peracetylation (Scheme 2). Treatment of the silyl protecting group with an excess of

Complete transfer of chirality in an intramolecular, thermal [2 + 2] cycloaddition of allene-ynes to form non-racemic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2011, 7, 601–605, doi:10.3762/bjoc.7.70

• commenced with the preparation of the enantiopure propargyl acetate 7 [8]. Treatment of racemic propargyl alcohol 4 with the (R)-acid chloride 5, DMAP, and pyridine resulted in propargyl ester 6 as a separable 4:1 mixture of diastereomers. Saponification of the major diastereomer of 6, followed by acylation