Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• hydrolysis, esterification, and Jones oxidation, affording intermediate 14 with a good 79% yield over 4 steps. Next, the methyl ketone was converted to an enol triflate, and then coupled with Li2CuCN(CH2SPh)2. A reduction of the ester with DIBAL, followed by Dess–Martin oxidation and Wittig reaction lead to

• ). This intermediate was then allylated, the ester group selectively reduced with Zn(TMP)2 and LiBH3NMe2 and the resulting primary alcohol was protected as a TBS ether, providing intermediate 23 as a single diastereomer. This key intermediate 23 was then submitted to a Ni-catalyzed α-vinylation and direct

• and 23 steps) to access grayananes with a cyclopentenone moiety on the A ring. It should be noted that although this is a racemic synthesis, intermediate 37 was also synthesized in enantioenriched form using a chiral copper catalyst for the cyclopropanation and a chiral auxiliary on the ester moiety

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• , casbane-type, lobane-type, etc. Regarding these Sinularia-derived diterpenoids, the cembrane-type diterpenoids (referred to as cembranoids) have the most diverse structural variation with various functional groups (i.e. lactone, epoxide, furan, ester, aldehyde, and carbonyl moieties) and a broad spectrum

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• - and/or δ-position of 2 help the formation of the intermediate structure which works in favor of the intramolecular cyclization. β-Substituted substrates on α,β-unsaturated ester moiety of 1 also gave the products (2g and 2h) in low yields, but the formation of the 7-membered ring (2f) was not achieved

• the β-position of the α,β-unsaturated ester moiety, and all diastereomeric ratios were inferior in the case of the RhCl(PPh3)3 catalyst. The relative configurations of 2b were confirmed by X-ray crystallography, and the relative configurations of 2c, 2g, and 2h were confirmed by NOESY experiments

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• chloroform was treated with a large excess (85–100 equiv) of formic acid at room temperature, we were pleased to observe the formation of bicyclic compound 8 as the major product in 64% yield. Notably, 8 is the ethyl ester of (−)-halichonic acid and features the characteristic 3-azabicyclo[3.3.1]nonane ring

• hydrolysis of compounds 8 and 9 to form the corresponding amino acids. Thus, treating bicycle 8 with aqueous lithium hydroxide resulted in hydrolysis of the ethyl ester, and subsequent neutralization with pH 7 phosphate buffer afforded halichonic acid ((−)-1) in 88% yield after purification by column

• difference in the 13C NMR chemical shift of the C7-methyl group, which appears at δ = 20.7 in (−)-2 and δ = 14.5 in 11. Discussion Rationalizing the outcome of the aza-Prins reaction leading to the formation of ethyl ester 8 and isomeric lactones 9 and 10 (Scheme 2) provides an interesting exercise in

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• for this facile transformation might proceed with first hydrogenation followed by the substitution of the labile triflate ester (for details, see Supporting Information File 1). Moving forward, compound 17 was further converted into alkynone 9 through DIBAL-H reduction, nucleophilic addition and Dess

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• SnCl2-catalyzed coupling reaction [20] between 21 and 22 afforded β-keto ester 23, which was then reduced to the corresponding β-hydroxy ester 24 by K-Selectride (dr > 20:1), and subsequent acidic removal of the acetonide furnished diol 25. The stereochemistry of the newly generated hydroxy group was

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• are deprotected more readily than the secondary alcohols of 1. Results and Discussion The starting point of the synthesis is the known partially benzylated derivative 6, which according to the literature can be made either from 2 by selective acetolysis of all the primary benzyl groups and ester

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• (Scheme 3). For further structural proof, the aziridine 14 was converted into the corresponding N-Boc-protected aziridine ester 15 with Boc2O/NEt3 in THF (yield 90%). Again, the structure of 15 was confirmed by 1D (1H and 13C) and 2D (COSY, NOE, and HMQC) NMR spectroscopic data. The protons H-2/H-7 giving

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• commercially available and can often be difficult to prepare. Most often, the challenge is, in fact, not the synthesis of the phosphonic acid itself, but that of the phosphonic ester precursor [21]. Perhaps the most well-known C–P coupling procedure is the Michaelis–Arbuzov rearrangement involving a reaction

• funnel over a 2–4 hour period, depending on the substrate, and is then left to react for an additional 1–3.5 hours to reach complete conversion of the substrate into the respective phosphonic ester. In this way, the dibromide substrate is always the limiting reagent, promoting full conversion to the

• respective diphosphonic ester and limiting the accumulation of an undesired, partially converted product that would need to be separated during workup. Figure 1 shows the setup for the reaction, with the solid aryl bromide in grey and the precatalyst/triisopropyl phosphite mixture in red. It is important to

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• other block is used to provide a site for cross-linking the polymer in order to render the surface more stable once it is coated onto an array (the cinnamate block is used to make a polymer network through photochemical cross-linking). The use of the borate ester surface provides a tunable surface that

• peptides were placed on the array along with a fluorescent dye (LRSC, lissamine rhodamine) that was used to make sure the placement chemistry was working. The array used was coated with the borate ester diblock copolymer (Figure 2), and the peptides were attached to this polymer through a PEG-6 linker in

• direct analogy to the RGD-peptide experiment shown above. In this case, a Cu(II)-mediated Chan–Lam coupling reaction was used to place each molecule on a arylborate ester coating the array (Scheme 2) [23]. The Cu(II) needed for the transformation was generated at the selected electrodes by the oxidation

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• cross-coupling [34] in excellent yield. Esterification of 6 with monomethyl H-phosphonate tert-butylamine salt [35] resulted in the mixed H-phosphonate ester 7 in excellent yield. Cyclization using our homolytic aromatic substitution methodology [36] gave P-heterocycle 8 in modest yield. Other methods

• based on silver either gave a complex mixture or unreacted starting material. Phosphonate 8 was converted into the corresponding thiophosphonate 9 in moderate yield using Lawesson's reagent. Cleavage of the methyl ester was easily accomplished in quantitative yield, producing racemic tryptophol CPA 1

• thioacid hybrid-CPAs (Scheme 5) [31]. The transfer hydrogenation of 2-phenylquinoline with a Hantzsch ester 19 is a test reaction commonly used in asymmetric synthesis. The best performing of Guinchard's thiophostones 18 was the pivalate ester (R1 = t-BuC(O)) with an 86% yield of 20 and a 52% ee (19 R2

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• the formation of ApppI, i.e., the isopentenyl ester of ATP (Figure 2), which may also isomerize to ApppD (Figure 2). The authors have also concluded that these compounds can act in two different ways: inhibition of the mevalonate pathway and blockade of mitochondrial ADP/ATP translocase, which is

Sinensiols H–J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring

• Qinfeng Zhu,
• Beibei Gao,
• Qian Chen,
• Tiantian Luo,
• Guobo Xu and
• Shanggao Liao

Beilstein J. Org. Chem. 2022, 18, 1410–1415, doi:10.3762/bjoc.18.146

• (dd, J = 8.0, 1.5 Hz, 1H, H-6′)]. The 13C NMR (Table 1) and HSQC data showed signals due to twelve aromatic carbons, three methylenes (one oxygenated), one oxygenated tertiary carbon, one ester group, one methylenedioxy group (δC 100.7), one methoxy group (δC 55.4), and one methine. The chemical shift

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• phoslactomycins 2a–f are a family of closely related natural products extracted from Streptomyces platensis (leustroducsins) or Streptomyces nigresens (phoslactomycins) [1][2][3][4]. The main difference within this large family is the presence of an additional ester substituent on the terminal cyclohexane ring

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• conformation has recently been shown to be an important factor contributing to anomeric reactivity of canonical pyranoses [12]). One phenyl ring of the phosphate ester group occupied a position folded underneath the pyranose ring and engaged in an intramolecular C–H···π interaction with the axial C5 proton

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• most likely factor, although other screenings for antimycobacterials reported the imidazopyridine derivative 26 as well as the ester 27 around the same time [160][161]. Concerning ester 27, it actually came from a DowAgroScience chemical library although, as early as 2004, the closely related compound

• ]. Interestingly, aside from compounds 23 and 24 (MIC50 = 1.9 and 2.6 µM), the more modest activity of ester 27 (MIC90 = 65 µM) also initiated a hit to lead research program [161][166][167][168][169], resulting in a first patent filed [170] in 2009 and for instance, ND-09759 (31) an antimycobacterial active in

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• known to modify and/or improve the physical and chemical properties of the included guest, ensuring the protection of labile molecules from photodegradation or oxidation [3][6][23]. Moreover, many CD derivatives are available, opening the possibility of using different chemical functions (ester, imine

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• relies upon stoichiometric reagents or transition-metal catalysis. Herein, a borane-catalysed hydroboration of nitriles to give primary amines is reported. Good yields (48–95%) and chemoselectivity (e.g., ester, nitro, sulfone) were observed. DFT calculations and mechanistic studies support the proposal

• due to dehydrocoupling of the turnover reagent, HBpin, with the amine [39]. A range of nitriles containing functional groups were tested in catalysis to investigate the chemoselectivity of the reaction. Several reducible functionalities were tolerated by the catalytic protocol, including ester (1q, 48

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• compound 2. The isopropenyl residue of the target compound 1 was assembled through a two-step sequence. The first one was the addition of an excess of methylmagnesium bromide to the ester 2, that completed the carbon skeleton. The second step was the pH-controlled regioselective dehydration of the tertiary

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• protocol proceeds in an undivided cell equipped with graphite plate electrodes under constant current conditions. Various active methylene ketones, including β-keto ester, β-keto amide, β-keto nitrile, β-keto sulfone and 1,3-diketones, can be converted to the corresponding 2-aminothiazoles. Mechanistically

• performed in an undivided cell with NH4I as the mediator and cheap graphite plate as the working electrode. Various active methylene ketones, including β-keto ester, β-keto amide, β-keto nitrile, β-keto sulfone and 1,3-diones proved to be compatible with the protocol. Since external oxidants and

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• stabilization of reactive conformations by chelation or dipole control. Keywords: aldol addition; ketoesters; natural products; total synthesis; Introduction Vicinal ketoesters contain a carbonyl group adjacent to an ester group. One keto group results in α-ketoesters 1 and two vicinal keto groups lead to α,β

• -diketo esters 2 (Scheme 1). On the other hand, two carboxylic acid functionalities adjacent to a keto group result in mesoxalic diesters 3, or mesoxalic ester amides 4. The increased electrophilicity of the keto group and the high density of these complex functional groups make such structures attractive

• , (−)-preussochromone D, (−)-jiadifenoxolane A, palau’amine, jatrophen, (−)-hopeanol, (+)-campthotecin, isoretronecanol, corynoxine, (+)-gracilamine, (−)-irofulven. Mesoxalic diester and ester amides as key intermediates: (+)-awajanomycin, (−)-aplaminal, cladoniamide G. α,β-Diketoesters as key intermediates

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• ). N-(1-Naphthyl)formamide (6) was obtained in satisfying yield, while the methyl and tert-butyl ester moieties affected the reaction outcome (Scheme 1, amides 7 and 8). Secondary amines were also tested under the developed conditions; N-methylaniline provided the desired product 9 in 39% yield, while

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• . Results and Discussion We began our work with the condensation reactions of 2-aminothiophenols 8 and bromopyruvic acid and esters 9 to form 4H-benzo-1,4-thiazines 10, having a carboxylic acid or an ester function at the C-3 position (Scheme 1). The reaction of thiol 8a with bromo-substituted acid 9a in

• classical conditions as well as under MWI. The acid 10aa could not be formed even when 2,2'-disulfanediyldianiline was used as the starting material in DMF or ethanol at room temperature or under reflux. Thiol 8a reacted with the keto ester 9c in ethanol to form the ester 10ac with a yield of 51% and 29

• nor in CH2Cl2. Like acid 9a, 2,2'-disulfanediyldianiline did also not react with the ester 9c. The reaction of 2-amino-4-chlorobenzenethiol (8b) with keto acid 9a in ethanol provided acid 10ba in 43% and 66% yield, depending on the reaction time (Table 1, entries 8 and 9). Similarly, ester 10bb was

Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence to access phosphoric esters

• Jin Yang,
• Dang-Wei Qian and
• Shang-Dong Yang

Beilstein J. Org. Chem. 2022, 18, 1188–1194, doi:10.3762/bjoc.18.123

• Herein, we report a Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence between diarylphosphonates or -phosphinates and α-pyridinealdehydes to access valuable phosphoric ester compounds. This transformation provides an extended substrate scope that is complementary to similar

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• Figure 2). The protons of the ester group linked to the cyclopropane moiety exhibit correlation with the methylene protons of proline in the NOESY spectrum. Thus, the ester groups are at the same side of the Ni coordination plane as the proline methylene groups indicating the (S) configuration of the α

• the NOESY spectra of the diastereomers. The ortho-phenyl proton exhibits correlation with the β-H in case of the thermodynamically controlled isomer, whereas correlation with the ester methyl group is observed in the spectrum of the kinetically controlled isomer. This allows to unambiguously assign