Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• . Review Syntheses Kumaraswamy’s approach to brevipolide H (8) In 2014, Kumaraswamy and co-workers initiated the first attempt to synthesize brevipolide H (8, Scheme 1) [14]. In the retrosynthesis, the target compound 8 is achieved via esterification of the β-hydroxycyclopropyl intermediate 16 with the

• epoxide using vinyl Grignard reagent followed by esterification with acrylic acid (35) proved to be inefficient due to low reproducibility and poor isolation of product 36. The strategy was altered by changing the terminal epoxide 34 to an allylic alcohol (95%) utilizing dimethyl sulfonium methylide

• followed by esterification with 3-butenoic acid (37) under Steglich conditions (Scheme 3). The resulting product 38 was isolated in 86% yield. A subsequent ring-closing metathesis reaction and DBU-assisted double bond migration then furnished the anticipated structure 39. The PMB functionality was removed

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

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

• mono-esterification of substituted malonic acids. Indeed, this approach has been only used by Fukumoto for the preparation of (−)-menthyl-derived SMAHOs [51][52]. We began this study by preparing various substituted malonic acids 9 through the saponification of the corresponding substituted malonates 3

• sensitive functional groups and limits the degree of substitution of the ester function. This last limitation could be circumvented using the mono-esterification of malonic acid derivatives, which gives access to a broad range of derivatives. Overall, this work presents the different possibilities to access

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• yield. The first step involved esterification of malic acid using methanol, followed by selective reduction of the resulting dimethyl ester using borane dimethyl sulfide (BMS) yielding diol 5 (Scheme 2) [1][14][15]. The step achieved chemo-differentiation of the carboxyl groups present in 3 whilst

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• -pong second (ketone amination, diol esterification, desymmetrisation in the second half reaction); ping-pong first (diol ester hydrolysis) and ping-pong both (prochiral diacids). For plausible values of enzyme kinetic parameters, the product enantiomeric excess (ee) can decline substantially as the

• are the reduction of prochiral ketones to chiral secondary alcohols, transamination of prochiral ketones to chiral amines, hydrolysis of symmetrical diesters to a chiral monoester, and esterification of prochiral diacids or diols. In desymmetrisation reactions, the enzyme initially produces the two

• , both”. Followed in most lipase or esterase reactions of prochiral diacids: either hydrolysis of their esters, or esterification of the free acids. The enzyme reacts enantiospecifically with the ester or acid. But now the acyl enzyme can be in either stereoisomeric form, so the kinetics are different

Chiral isothiourea-catalyzed kinetic resolution of 4-hydroxy[2.2]paracyclophane

• David Weinzierl and
• Mario Waser

Beilstein J. Org. Chem. 2021, 17, 800–804, doi:10.3762/bjoc.17.68

• transformation into diastereomers by esterification with chiral acid chlorides [19][20] as well as the kinetic resolution (KR) of racemic esters of 2 via an enzymatic hydrolysis [25][26][27] were very successfully used to access enantioenriched 2. Recently, Akiyama and co-workers reported the kinetic resolution

• of rac-PHANOL (4,12-dihydroxy[2.2]paracyclophane) by means of a chiral phosphoric acid-catalyzed esterification with achiral anhydrides [28]. This method allowed for high s-factors but was unfortunately not satisfyingly applicable to rac-4-hydroxy[2.2]paracyclophane (rac-2) [28]. Considering the

• interest in compound 2, we thus thought about developing an alternative organocatalytic kinetic resolution protocol to control the esterification of rac-2. Chiral isothioureas (ITUs) emerged as easily available and powerful catalysts for numerous applications [29][30][31][32] and have been very

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• methanofullerene-appended dicarboxylic acid 85 synthesized from 10 is a versatile synthon for conversion into numerous derivatives (Scheme 25). The reactivity of compound 85 was studied under DCC-promoted esterification conditions (see adducts 8 and 86) and amidation conditions (see adducts 21 and 22). Hummelen

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• enantiospecific synthesis of two artificial glutamate analogs designed based on IKM-159, an antagonist selective to the AMPA-type ionotropic glutamate receptor. The synthesis features the chiral resolution of the carboxylic acid intermediate by the esterification with ʟ-menthol, followed by a configurational

• ], the heterotricyclic framework was constructed over a five-step sequence including the domino metathesis reaction as a key step to give (rac)-7. The subsequent three steps from (rac)-7 (esterification with CH2N2, PMB removal, and ester hydrolysis) had been proven to be promising for the preparation of

• be effective here (Scheme 2). Thus, the esterification mediated by 2-methyl-6-nitrobenzoic anhydride (MNBA, Shiina esterification) [9], followed by chromatographic separation of the diastereomers, successfully generated the (2S)-isomer 9* (tR 7.0 min) and the (2R)-isomer 9 (tR 11.5 min) in 45.3% and

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• reacted with benzyl (R)-lactate ((R)-26b) or benzyl (R)-2-phenyllactate ((R)-26f). The optically active phosphonodepsidipeptides 28 were obtained after hydrogenolysis and tested for their biological activity (Scheme 5) [22]. The phosphonodepsidipeptides 31 were synthesized by the esterification of N-Cbz

• tryptophan amide with 4-nitrobenzyl (R)-N-Fmoc 1-amino(cyclohexyl)methylphosphonochloridate (38), which was prepared from diethyl (R)-N-Fmoc 1-amino(cyclohexyl)methylphosphonate (36) via a selective basic hydrolysis, chlorination, esterification with 4-nitrobenzyl alcohol, selective basic hydrolysis, and

• nucleophilic esterification of potassium 1-(N-benzyloxycarbonylamino)alkylphosphonates 172 with alkyl halides in the presence of 18-crown-6. They also prepared a phosphonodepsidipeptide 174 with ethyl chloroacetate (173) as an electrophile (Scheme 33) [53]. The macrocyclic peptidyl phosphonodepsipeptide 180

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• utilized as it is frequently used for esterification reactions [26][27][28]. CALB could convert benzyl alcohol in the presence of vinyl butyrate into benzyl butyrate and acetaldehyde. To demonstrate the feasibility, the flow process was adapted by mixing a stream of vinyl butyrate (4, 3 equiv in toluene

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• the primary hydroxy group compare favorably with the previously reported overall yield (46 and 47%, respectively, in three steps) [15][16][17][29], which relate to the selective enzymatic O-5-deacetylation and esterification of the primary hydroxy group and a final deprotection of the 2,3-O-acetyl

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• hydrogenation of difluorocyclopropenes [73][79]. Enzymatic hydrolysis or esterification: The first example of the enzymatic resolution of gem-difluorocyclopropanes was reported by Itoh et al. [80]. The prochiral diacetate of cis-1,2-bis-(hydroxymethyl)-3,3-difluorocyclopropane was converted into the

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• macrocycle has inherent chromophores that can function as photosensitizers, the efficiency of the energy transfer will be higher and the systems will be simplified. 3) Other kinds of macrocycle-based catalysis need to be explored, such as esterification, polymerization, redox reaction, etc. 4) Hyperbranched

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• intact. Commonly this heterofunctionalization is achieved using esterification of trimesic acid and subsequent partial hydrolysis, however, this route suffers from difficult purification steps [37][38]. Here, it was conveniently achieved in one step via a solid-phase supported approach, using trimesic

Chemical constituents of Chaenomeles sinensis twigs and their biological activity

• Joon Min Cha,
• Dong Hyun Kim,
• Lalita Subedi,
• Zahra Khan,
• Sang Un Choi,
• Sun Yeou Kim and
• Chung Sub Kim

Beilstein J. Org. Chem. 2020, 16, 3078–3085, doi:10.3762/bjoc.16.257

• obtained by geometry optimization at the MMFF force field. (C) ECD spectrum of 1 and structures of 1 (6S) and 13 (6R). (D) Enzymatic hydrolysis of 1 followed by modified Mosher’s esterification of the aglycone 1a. 1H [ppm, mult., (J in Hz)] and 13C NMR data of compounds 1 and 1a in methanol-d4

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

• Thomas Holmstrøm,
• Daniel Raydan and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2020, 16, 2788–2794, doi:10.3762/bjoc.16.229

• with high regioselectivity via the Černý epoxide [20]. Results and Discussion Synthesis The synthesis was initiated by a regioselective esterification of levoglucosan (1) with tosyl chloride in pyridine, first presented by Černý and co-workers, in order to afford the 1,6-anhydro-2,4-di-O-tosyl-β-ᴅ

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• the amino alcohols 10a–d were protected with a Boc group [42][43]. Esterification of the protected alcohols 11a–d [33][44] with 2,3-dioxosulfinylbenzoyl chloride obtained from 2,3-dihydroxybenzoic acid and thionyl chloride afforded the N-Boc-substituted catechol ligands 12a–d [33][36]. They were

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• common organic solvents, they first tried the esterification reaction with soluble monoiodosumanene 79 using Pd(OAc)2 under CO atmosphere and obtained the desired sumanene methyl ester in very low yield. Surprisingly, when they used hexabromosumanene 94 under similar reaction conditions, no product

• formation was observed. Therefore, they used a Pd-catalyzed carbonylative esterification in the presence of phenyl formate which in situ generated CO and phenol to provide the required product 97 in 73% yield (Scheme 24). In an independent work reported in 2017, Fukushima and co-workers detailed the

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• study is 4-(N,N-dimethylamino)pyridine derivative 1 (Figure 1). The parent 4-(N,N-dimethylamino)pyridine (DMAP, 2) is known as a nucleophilic catalyst in a number of reactions, for example the Baylis–Hillman reaction [27] and the Steglich esterification [28][29]. To achieve control of the catalytic

Muyocopronones A and B: azaphilones from the endophytic fungus Muyocopron laterale

• Ken-ichi Nakashima,
• Junko Tomida,
• Tomoe Tsuboi,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 2100–2107, doi:10.3762/bjoc.16.177

• MTPA chloride, enolization and esterification at the C-15 position occurred preferentially over the C-3′ position. Therefore, 2.7 equivalents of the (R)- and (S)-MTPA chlorides were used to prepare the (S)- and (R)-MTPA diesters 1a and 1b, respectively (Scheme 1A). Based on the differences in chemical

Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

• Abimelek Cortes-Pacheco,
• María Adelina Jiménez-Arellanes,
• Francisco José Palacios-Can,
• José Antonio Valcarcel-Gamiño,
• Rodrigo Said Razo-Hernández,
• María del Carmen Juárez-Vázquez,
• Adolfo López-Torres and
• Oscar Abelardo Ramírez-Marroquín

Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108

• [23]. Then, the above-named derivatives were synthesized in a first stage by the esterification of bromoacetyl bromide and the corresponding alcohol. The reaction of ethyl or tert-butyl alcohol and bromoacetyl bromide in the presence of triethylamine in CH2Cl2 yielded the bromoaceto esters 7 and 8 in

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• affecting the newly introduced fluorine atom was attempted by a two-step, one-pot protocol involving an in situ esterification of a highly electrophilic pyridinium triflate intermediate [77] and afforded the anti-β-fluoro-α-amino acid methyl ester 160a in 52% yield and with 98.8% ee (Scheme 39). On the

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• compound 8 involves the amidation of 18β-glycyrrhetinic acid followed by the esterification with acetic anhydride. Finally, compound 8 underwent N-Boc deprotection to prepare product 4. To ascertain the scope of the reaction, another C-3 ester derivative 17 was tested under the optimized reaction

• yield. The reaction was completed in 30 min. The principal advantages of this method are that there is no solvent required, and that the reaction time is shorter than in previous cases [16], since the acid formed during the reaction may catalyze the esterification reaction of 18β-glycyrrhetinic acid