(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• development of a new synthetic route to diester 1,2-cubane 88 from dimethyl cubane-1,4-dicarboxylate (85) (Scheme 9A) [51]. 1,4-Cubane 85 is photochemically carboxylated to 86, and selective saponification of the least hindered ester leads to 87. Formation of a redox active ester followed by photocatalytical

• , respectively (Scheme 12B) [58]. Saponification of the ester moieties in these species followed by Curtius rearrangements then led to amines 114 and 116. Non-natural amino acid derivatives 113 and 117 are intermediates prepared using these methods that could be of interest to medicinal chemistry. Alcohol 111

• sequence of saponification (to 127), decarboxylative halogenation (to 128 and 130) and strain-inducing substitution then forms [3.1.1]propellane (129). Anderson and co-workers have reported a new synthesis of [3.1.1]propellane (129) based on the dibromocyclopropanation methodology typically used to access

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• ester 5 was coupled with the carboxylic acid (S)-8, derived from ʟ-leucine ((S)-6) via hydroxyacid (S)-7, to yield the amide (S)-9. Deprotection through catalytic hydrogenation to (S)-10, saponification of the acetate ester and Steglich esterification with N-acetylcysteamine gave access to the desired

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• alcohol with iodoethane and the transformation of the t-Bu ether in acetyl ester following the method of Ganem and Small [141], produced, after saponification, the key intermediate 31.6. In 1993, Pinchuk reported a stereocontrolled synthesis of both enantiomers of analogues of edelfosine featuring a C18:1

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• commercially available, methyl linoleate, having the same degree of unsaturation with a longer chain length by two carbons, was used as a source of the acyl chain. Linoleic acid, obtained by saponification of methyl linoleate, was condensed either with (R)- or (S)-solketal (isopropylidene glycerol) by Steglich

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• a Z/E ratio of 95:5. Additionally, the authors developed an alternative synthesis of civetone (69) by metathesis of ethyl 9-decenoate and subsequent Dieckmann cyclization in flow, followed by a saponification and decarboxylation process in batch providing (Z)-civetone in 48% yield over three steps

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• ester group at C5 and an alkyl group at C6 position. A group of researchers from Merck reported the synthesis of 5-unsubstituted DHPMs via a Biginelli reaction followed by saponification of the ester and subsequent decarboxylation [22]. Later, Bussolari and McDonnell demonstrated the synthesis of 5

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• further reacted with potassium cyanide to yield nitrile 12 [27]. Saponification of the nitrile was performed by exploiting the Pinner reaction with saturated HCl gas in methanol. This led to methyl indol-2-ylacetate (13) in 83% yield [28]. The hydrolysis of ester 13 was performed in the presence of

• batch of 1a was reduced. It is likely that 2a can be cyclized by base catalysis, or by using common peptide coupling reagents (e.g., EDCI, HATU) upon saponification of the ester group. However, we opted for a trimethylaluminum-mediated amidation reaction [4][39] to give rise to 8-benzyl-7-hydroindolo

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• –125, Li et al. utilized a ring-contracting α-iminol rearrangement to diastereoselectively install the spiroindolinone moiety that served as a key common intermediate (Figure 22) [32]. The rearrangement was triggered by saponification of the benzoyl ester in 126, resulting in a 90% yield of 127

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• intermediate Meldrum acid. Both these transformations are characterized by their simplicity and efficiency, allowing a straightforward access to SMAHOs from cheap starting materials. Keywords: alkylation; esterification; malonate; saponification; SMAHO; Introduction Malonic acid half oxyesters (MAHOs), also

• MAHOs [24][25][26][27]; and a Michael addition for 3'-oxoalkyl-substituted MAHOs [28]. As studied by Niwayama [29], the hydrolysis step is generally achieved by saponification using alcoholic KOH (or NaOH) [30][31][32][33][34][35][36], but other selective cleavages of one ester group are possible [37

• synthetic routes. Results and Discussion Substituent modification – alkylation/saponification route Based on the literature precedents, it appeared logical to start the preparation of SMAHOs by the alkylation of a malonate derivative followed by a monosaponification of the resulting diester. This strategy

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• role in the selective formation of 3, but the exact operation of O2 during this process remains unclear at this stage. A tentative pathway for the formation of compound 4 is proposed in Scheme 5. It is well documented that with a dilute amount of base, ester hydrolysis followed by saponification takes

Decarboxylative trifluoromethylthiolation of pyridylacetates

• Ryouta Kawanishi,
• Kosuke Nakada and
• Kazutaka Shibatomi

Beilstein J. Org. Chem. 2021, 17, 229–233, doi:10.3762/bjoc.17.23

• achieved using N-(trifluoromethylthio)benzenesulfonimide as the electrophilic trifluoromethylthiolation reagent. The reaction afforded the corresponding trifluoromethyl thioethers in good yield. Furthermore, the preparation of lithium pyridylacetates by saponification of the corresponding methyl esters and

• lithium pyridylacetates undergo decarboxylative fluorination upon treatment with an electrophilic fluorination reagent to afford fluoromethylpyridines under catalyst-free conditions. Furthermore, we demonstrated the one-pot synthesis of fluoromethylpyridines from methyl pyridylacetates by saponification

• trifluoromethylthiolated product at all, despite complete saponification of the methyl ester. Conclusion In conclusion, we demonstrated the decarboxylative trifluoromethylthiolation of lithium 2- and 4-pyridylacetates to synthesize pyridine derivatives with a trifluoromethylthio group at a tertiary carbon center adjacent

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• . Stille coupling of (Z,Z)-(rac)-62 with vinyl iodide 48 in the presence of Pd(CH3CN)2Cl2 in DMF proceeded smoothly to give the corresponding ester (triene isomerization was less than 20% during coupling), which was then converted into acid derivative (rac)-63 by saponification. Finally, the acid

• derivative (rac)-63 was subjected to undergo acetylation, acid chloride formation, and quenching with ammonium hydroxide to produce amide derivative (rac)-64 in 70% yield. Finally, saponification of acetate (rac)-64 using lithium hydroxide gave racemic inthomycin A ((rac)-1) in 14% overall yield (Scheme 5

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• -substituted thienopyrrole 26, saponification to carbonic acid 27, and subsequent Cu-mediated decarboxylation in quinoline resulted in thienopyrrole 28 in more than 80% yield over three steps. Lithiation of 28 with n-BuLi and reaction with TIPS chloride selectively occurred at the thiophene α-position to give

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• ) was the linking step, and ester saponification was the cutting step. A potential problem with this approach was that the macrocycles were highly flexible and thus they might adopt a closed conformation hindering the necessary threading step. The flexible tails made the compounds soluble, but also

• alkyne–azide click cycloaddition as the linking step, and ester saponification as the cutting step [13][21] (Supporting Information File 1). The target trefoil knot using host 1 and guest 2 is shown in Figure 2c. The binding event during the double-threading step was modeled after previous literature

• 13 which was identical to the material made by the route outlined in Scheme 2. The new route from 6 to 13 proved superior, as the yield for the two-steps improved dramatically from <8% to 71%. Saponification of diester 13 to diacid 15 was achieved in moderate-to-good yields (67–90%) and the 1H NMR

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• -naphthaldehyde, trimethylsilyl trifluoromethanesulfonate (TMSOTf), and triethylsilane (Et3SiH) [17][19]. On a 10 g scale, the protected methyl ester 6 could be purified by recrystallization followed by filtration to remove the major byproduct 2-methylnaphthalene. Subsequent saponification of the methyl ester 6

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• -thiobenzoylaminobutanol in 62% yield [57], and the second one is not applicable to N-thioaroyl derivatives [58]. Thus, a diacylation–thionation–saponification sequence [59] was implemented (Table 1), and the individual steps optimized using 4-aminobutanol and benzoyl chloride as the starting materials. The diacylation

• conversion to the desired product. Saponification of the less reactive isobutyryl and pivaloyl derivatives 2l,m required the use of a stronger base, longer reaction times and higher temperature (10% NaOH, reflux, 4 h). The overall output of the optimized sequence (Table 1, last column) ranged from 69 to 85

Synthesis of aryl-substituted thieno[3,2-b]thiophene derivatives and their use for N,S-heterotetracene construction

• Nadezhda S. Demina,
• Nikita A. Kazin,
• Nikolay A. Rasputin,
• Roman A. Irgashev and
• Gennady L. Rusinov

Beilstein J. Org. Chem. 2019, 15, 2678–2683, doi:10.3762/bjoc.15.261

• of 5- or 4-aryl-3-chlorothiophene-2-carboxylates, respectively, with methyl thioglycolate in the presence of potassium tert-butoxide. The saponification of the resulting esters, with decarboxylation of the intermediating acids, gave the corresponding thieno[3,2-b]thiophen-3(2H)-ones. The latter

• toluene/ethanol mixture (1:1, v/v), or pure toluene for compounds 3f,g,i. Next, we performed saponification of esters 3a–k by their treatment with an excess of sodium hydroxyde in an aqueous DMSO solution at 120 °C for 3 hours, where the intermediating acids underwent decarboxylation to give thieno[3,2-b

• yields of products 4 because of their partial degradation. Therefore, to neutralize the reaction mixtures, we used one equivalent of sulfuric acid relative to the alkali salt used for saponification. The resulting precipitates were then isolated by filtration, and thoroughly washed with water. As a

Photochromic diarylethene ligands featuring 2-(imidazol-2-yl)pyridine coordination site and their iron(II) complexes

• Andrey G. Lvov,
• Max Mörtel,
• Anton V. Yadykov,
• Frank W. Heinemann,
• Valerii Z. Shirinian and
• Marat M. Khusniyarov

Beilstein J. Org. Chem. 2019, 15, 2428–2437, doi:10.3762/bjoc.15.235

• a cyclopentene bridge with 51% yield. Robinson-type reaction [37] of ethyl 4-(2,5-dimethylthiophen-3-yl)-3-oxobutanoate and chalkone 5 resulted in cyclohexenone derivative 6 (57% yield). The saponification/decarboxylation of 6 gave cyclohexenone 7. Thus, the previously developed methodology was

Mono- and bithiophene-substituted diarylethene photoswitches with emissive open or closed forms

• A. Lennart Schleper,
• Mariano L. Bossi,
• Vladimir N. Belov and
• Stefan W. Hell

Beilstein J. Org. Chem. 2019, 15, 2344–2354, doi:10.3762/bjoc.15.227

• closed form (formed by handling in the lab not fully protected from light) were detected by HPLC (Figure S33 in Supporting Information File 1). The constitution, structures, and purities of the final products were confirmed by HRMS, 1H and 19F NMR spectroscopy, as well as analytical HPLC. Saponification

• atmosphere, an emulsion of the starting compounds, Pd2(dba)3, P(Cy)3 stock solution, and aqueous K2CO3 in THF (see Supporting Information File 1 for details). Saponification of methyl ester groups in tetraester SyTh2 leading to tetracarboxylic acid SyTh2-H. Optical properties of the photochromic DAEs (in

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• corresponding carboxylic acid followed by hydrogenolysis with H2/Pd-C led in spontaneous lactonization to give the key butenolide 66. Oxidation of 66 with CrO3/AcOH–H2O, followed by saponification and reduction afforded known benzyl alcohol 46 (19% from 66). Then, phenol 46 was converted to the corresponding

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• ]. The aziridine ring opening with acetic acid and saponification led to the formation of (S)-101. Protection of the vicinal aminohydroxy fragment as an oxazolidin-2-one provided (R)-104 which after selective debenzylation produced (R)-102. The synthesis of N-acetyl-3-phenylserinol ((1R,2R)-105) was

• cleavage of the aziridine ring occurred regiospecifically at the N–C3 bond (benzylic position) to provide N-Boc-ᴅ-phenylalaninol ((R)-118) after saponification. When mesylation of (2S,1'R/S,1''R)-28 was followed by LiAlH4 reduction the aziridine (2R,1'R)-119 was produced from which the acetate (2R,1'R)-120

• hydrogenation followed by saponification converted 178 into (2S,3S)-N-Boc-3-hydroxy-2-hydroxymethylpyrrolidine (2S,3S)-179, one of the simplest members of the iminosugar family. Reaction of aziridine 4-methoxyphenyl esters either (2R,1′S)-5e or (2S,1′S)-5e with vinylene carbonate at 280 °C gave a mixture of

An azobenzene container showing a definite folding – synthesis and structural investigation

• Abdulselam Adam,
• Saber Mehrparvar and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2019, 15, 1534–1544, doi:10.3762/bjoc.15.156

• steps according to a known procedure (Scheme 1) [51]. Therefore, the imidazole-containing acid 6 was reacted with the free amine 7 using pentafluorophenyl diphenylphosphinate (FDPP) as coupling reagent resulting in the formation of amide 8. After saponification of the methyl ester and removal of the Boc

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• saponification of the methyl ester. Boc-Tyr(3-B(OH)2,Me)-OH was coupled using DIPCDI and Oxyma in DMF for 3 h. An aliquot of the linear resin 7 was cleaved to provide H-Tyr(3-B(OH)2,Me)-Ala-Gln-Gly-Gln-Phe(4-I)-βAla-Gln-OpNB in 57% purity, which was characterized by mass spectrometry. Resin 7 was then subjected

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• with literature data we converted 7 to the free carboxylic acid carrying a TBS-protected hydroxy group at C8 by silylation with TBSOTf/2,6-lutidine, followed by saponification with LiOH. To investigate whether polyketide 7 could be coupled in an unprotected form with the peptide fragment of seragamide

• quantitative yield, albeit as mixtures of inseparable diastereomers (4:1), as consequence of the optical impurity of 22. Only when following the coupling order shown in Scheme 5, high yields could be obtained. The labile carboxylic acid 29 was formed by saponification of methyl ester 7 (LiOH, H2O/MeOH) and

• scale, desilylation of 31 (TBAF) was a spot-to-spot conversion. Saponification of both the silylated and desilylated methyl esters with LiOH was possible, as long as very mild acidic conditions were applied on work-up. However, macrocyclisation of the TIPS-protected or the desilylated acid did not occur

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