Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• ETD ESI-qTOF. Alltech Davisil (30–40 µm, 60 Å) C8-bonded silica and Alltech Davisil (30–40 µm, 60 Å) diol-bonded silica were used for pre-adsorption work before RP- or NP-HPLC, respectively. The pre-adsorbed material was subsequently packed into an Alltech stainless steel guard cartridge (10 × 30 mm

• phenyl-bonded silica (5 μm, 100 Å, 150 × 21.2 mm) and Phenomenex Luna C18 column (5 µm, 90–110 Å, 10 mm × 250 mm) were used for RP-HPLC separations. For NP-HPLC, a YMC diol-bonded silica (5 μm, 120 Å, 150 × 20 mm) column was used. The frozen marine sponge was dried using a Dynamic FD12 freeze dryer and

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• , [3]rotaxane diol 10 was used as the initiator of the controlled ring-opening polymerization (ROP) of ε-caprolactone in the presence of a diphenyl phosphate catalyst to introduce the polyester main chain into the rotaxane framework; the successive end-capping reactions yielded macromolecular [3

• ]rotaxane 11 (Figure 12). In this synthesis, the hydroxy groups on CDs were completely acetylated to facilitate ROP only from the axle-end diol moieties and increase the solubility of [3]rotaxane. Further, subjecting the polymer to heat treatment induced the deslipping of CDs from the central alkyl chain on

4,6-Diaryl-5,5-difluoro-1,3-dioxanes as chiral dopants for liquid crystal compositions

• Maurice Médebielle,
• Peer Kirsch,
• Jérémy Merad,
• Carolina von Essen,
• Clemens Kühn and
• Andreas Ruhl

Beilstein J. Org. Chem. 2024, 20, 2940–2945, doi:10.3762/bjoc.20.246

• range of chiral, twisted molecules such as binaphthyls [23][24][25], biphenyls [26][27], TADDOLs [16][17] and 1,2-diphenylethane-1,2-diol [28] to reveal possible relationships between the molecular structure of chiral dopants and their HTP value. However, quantitative structure–property relationships

• still remain elusive and are not well understood [29]. Recently we have become interested in the preparation of racemic [30] anti- and highly enantioenriched 2,2-difluoro-1,3-diols [30][31][32] through an acylative double catalytic kinetic resolution (DoCKR) process [33]. While the 1,3-diol motif is

• -1,3-diphenyl-1,3-propanediol (rac-2). These enantiomers were then evaluated as chiral dopants using two commercially available liquid crystal host mixtures (Host 1 and Host 2 from Merck KGaA) (Scheme 2). Results and Discussion Racemic anti-2,2-difluoro-1,3-diol rac-2 was easily prepared through a

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• underwent cyclization and dehydration to produce linked polyheterocyclic indoles 75. The authors managed to prepare five adducts in 15–33% yield. Another mechanistic scenario occurred at higher temperature (Scheme 25, conditions b). The secondary amine of diol 73 substituted both secondary alcohols to

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• diol 141 with chloroacetyl chloride, followed by cyclization induced by formation of the alcoholate. On the other hand, amino diol 141b was N-alkylated with methyl bromoacetate and then microwaved in the presence of potassium carbonate to obtain morpholinone 144 (Scheme 38). Romero-Hernández and Merino

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• , introduce hydroxy groups at C8 and C16 to produce FD-8β,16-diol (7), and BscE-catalyzed O-methylation generates the putative intermediate 8. The subsequent oxidative allylic rearrangement (8→9), catalyzed by the nonheme iron(II) and 2-oxoglutarate (Fe(II)/2OG)-dependent dioxygenase BscD, was a key step

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

•  1), we successfully conducted the desired sequence by raising the temperature to 100 °C to initiate ring opening, and employing a mild transesterification method for diol release [43][44][45]. Thus, we were able to isolate 3-amino-1,2-diol 21 in 49% yield. Conclusion Within this work, we

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• intramolecular Cannizzaro reaction while accomplishing the synthesis of the bicyclic core structure of proposed ottelione A (47) [85]. Commencing from the Diels–Alder adduct 48, an enzymatic desymmetrization of the reduced diol 49 formed the enantiopure 50 (ee >99%). A cascade of reaction sequences delivered the

• tetracyclic cage compound 51. Acetal opening in 51 afforded the keto-aldehyde 52 which underwent an intramolecular Cannizzaro reaction to give the trihydroxy acid 53, finally cyclizing to the lactone diol 54, elaboration of which led to the desired target (Scheme 18). An interesting application of the

• yield (92%) and formed the diol 77, after the removal of the Boc-protecting group, where the prochiral hydroxymethyl groups ultimately paved the way towards the natural products (Scheme 22). Bernhardson and coworkers developed a simple scalable route towards ertugliflozin (80), a C-glycoside containing

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• dehydrogenated secondary alcohols into ketone B and diol into aldehyde A. Further, aldol condensation occurred between the ketone and aldehyde and produced α,β-unsaturated ketone C, which was subsequently hydrogenated by complex Mn1-c, followed by allyl isomerization, which led to the formation of hydroxy ketone

• -membered ring products. They isolated cyclic five to seven-membered ring products by changing the lengths of the diols. For example, for the formation of cyclopentane products, butane-1,4-diol was used as the alcohol under the same reaction conditions, giving 31 to 70% yield of the desired products. Seven

• -membered rings were also formed only by changing the alcohols to hexane-1,6-diol under the same conditions as above, giving yields up to 80%. In addition, several ketones were investigated under these conditions with different diol systems, giving 55–80% yields of the cyclic products (Scheme 36). DFT

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• for 18 was more complicated, showing many more side products compared to other tested substrates (see Figure S7 in Supporting Information File 1). We hypothesize this is due to 18 undergoing a reaction in aqueous solutions to generate a geminal diol in place of an aldehyde, as has been previously

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• 13C{1H} NMR spectra contained signals supporting the presence of ketone (e.g., δC = 185.6 ppm for 5a) and ester (δC = 161.9 ppm for 5a) functionalities. Difluoroketoester products were found to hydrate readily to give gem-diol derivatives during aqueous work-up [39], thus reducing the efficiency of

• extraction. Indeed, attempts to grow a single crystal of 5e from a mixture of EtOH and water led to the isolation of the corresponding gem-diol (Figure 3). There are very few examples of organic structures containing a C(OH)2–CF2–C fragment in the CCDC and only three acyclic examples (CSD 5.43 (Nov. 2021

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• prepared from the known sialic acid derivative 5 [36] with an 8,9-O-isopropylidene group by a three-step reaction sequence (see Scheme 2). Exhaustive chloroacetylation of hydroxy groups in diol 5 with chloroacetic anhydride and 2,4,6-collidine in CH2Cl2 gave bis-chloroacetate 6 (90% yield), which was

• treated with 90% aq trifluoroacetic acid in CH2Cl2 to give diol 7 (70% yield) that was formed due to migration of a chloroacetyl group from O-7 to O-9. The structure of diol 7 was established by NMR spectroscopy, high-resolution mass spectrometry and X-ray diffraction analysis (see the Experimental

• section and Supporting Information File 1 for the details). Diol 7 was converted into glycosyl donor 2 by O-trifluoroacetylation with trifluoroacetic anhydride and sodium trifluoroacetate under previously developed [36][55] conditions. Supramer analysis As we know that the concentrations of reactants can

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• × 50 mm, Phenomenex), and Nucleosil 120 OH Diol (7 µm, 250 × 21 mm, Machery-Nagel, Düren, Germany) columns maintained at room temperature. Normal phase p-HPLC equipped with DAD detector (Agilent 1100 Series, Santa Clara, USA) was connected to a Nucleosil 120 OH Diol column. Deionized water used for RP

• fractions from the three repeated runs were combined to give three sub-fractions (D1–D3). All these sub-fractions D1 (12 mg), D2 (8 mg), and D3 (15.8 mg) were further separately purified over normal phase preparative HPLC with a DAD detector with a Nucleosil 120 OH Diol column (7 µm, 250 × 21 mm) used as

• , tR = 11.21 min), and 7 (1.45 mg, yellow neat solid, tR = 15.00 min), 4 (2.45 mg, white amorphous powder, tR = 22.00 min), respectively. Successive purifications of series F (898 mg) over normal (CH2CH2/MeOH 92:8, Nucleosil 120 OH Diol column) and reversed-phase preparative HLPC (Gilson, PLC 2020

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

• produces the diester 4.12 with an inversion of the configuration of the chiral carbon atom. Then, 4.12 was hydrolyzed in the presence of KOH to produce 4.10. The installation of the phosphocholine group was achieved following two schemes: a) Starting from the diol 4.10 (Figure 4C), tritylation and

• also achieved in the last step (Figure 5) [73]. DIBALH (diisobutylaluminium hydride) in toluene was added to hexadecanol in dichloromethane at 0 °C (Figure 5) to form in situ a lithium alcoholate. Then, S-glycidol was added at rt to produce in 50% yield the diol 5.2 after a regioselective opening of

• deprotection of diol with HCl, the aryl ether glycerol 10.3. The protection of the sn-2 position with a benzyl group was achieved by a classical tritylation of the primary alcohol, benzylation of the secondary alcohol and removing the trityl protecting group. The low yield of this three-step sequence is due to

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• . The known compounds are readily identified as eudesm-4(15)-ene-7β,11-diol (6) [17], rel-(2R,8S,8aR)-2-(1,2,6,7,8,8a-hexahydro-8,8a-dimethyl-2-naphthyl)propan-2-ol (7) [18], γ-costol (8) [19], (+)-9-hydroxyselina-4,11-dien-14-oic acid (9) [20] and 1β-hydroxyeremophila-7(11),9-dien-8-one (10) [21] by

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• ’-diol (SPINOL)-derived phosphoric acids with different substituents in the 2,2’-positions of the aromatic framework have been extensively explored as axially chiral catalysts in the field of asymmetric transformations including aza-Friedel–Crafts reactions. In 2018, Nakamura and co-workers designed an

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• a 1,5-anti induction of the aldol reaction [18][19][20] based on chiral alkoxy partner 9. Furthermore, it could be envisaged to reduce the resulting β-hydroxyketone 7 in a diastereoselective manner to obtain a 1,3-diol. This synthetic strategy could thus bring new stereochemical opportunities to

• %). This compound results from the transposition of the para-nitrobenzoyl (PNBz) group onto the 13-OH, which could be favoured by the steric hindrance of C-15 and a possible π–π stacking with the OPMB group. These PNBz esters were readily hydrolyzed to furnished diol 24 in 97% yield. The oxydation of the

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• yield diol 72. The 3R,4S configuration of compound 72 was expected based on Pettit’s work [16][17] and the optical purity of the obtained product was more than 95% by 1H NMR using [Eu(hfc)3] as a chiral shift reagent. Subsequent silylation followed by ester hydrolysis and removal of the pivaloyl group

• alcohol 143 with pivaloyl chloride [64] and subsequent dihydroxylation of the double bond in 144 according to the Sharpless protocol using AD-mix-β [65], furnished the required syn-diol 145 in 59% yield and >99% ee. The hydroxy groups were protected [66] as TIPS ethers 146 and treatment with DIBAL-H led

• to both, cleavage of the Piv group and reduction of the aldehyde yielding the diol 147. Selective oxidation [67] of the benzyl alcohol with MnO2 gave the compound 148, which was esterified with S-acetylthioacetic acid (129) and reduced to the benzyl alcohol 150. Deacetylation followed by

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• most intense peak (m/z = 991) (α), can be attributed to PEtOx chains that are terminated by a molecule of DLG diol with a potassium ion doping (Figure 3). However, α-distribution can also be attributed to DLG-initiated PEtOx. The presence of signals attributed to a polymer with a solvent fragment

• which interfere with the cationic ring-opening polymerization of 2-oxazolines (Figure 5). It has been reported that DLG can undergo keto–enol tautomerism and form enols or can participate in nucleophilic addition reactions [49]. Furthermore, it can react with water to its hydrated form, a geminal diol

• -diol terminating group carrying potassium and sodium ion doping, respectively. Signals at m/z = 3325 and m/z = 3341 could be attributed to methyl-initiated PEtOx with OH moieties carrying Na+ (δ) and K+ (γ), respectively. We also cannot exclude the possibility that these signals resulted from PEtOx

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

• , interconnection of the acyl and glyceryl units via an ester linkage was verified by three HMBC correlations from the terminal protons (H1, H2, and H1') of both units to the carboxy carbon (C1), leaving two protons to occupy C2' and C3' diol. Thus, compound 1 was determined to be a new monoacylglycerol and named

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• the commercially available 1,4-dithiane-2,5-diol (4) [26]. The diol 4 is commercially available in large quantities and is formally also a 1,4-dithiane derivative, but except for its dehydration to 1,4-dithiin, it is almost exclusively used as a source of mercapto acetaldehyde (of which it is a direct

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• was carried out through a two-step sequence including dihydroxylation (K2OsO4·H2O, 90% yield) of 8 and oxidative cleavage (NaIO4, 91% yield) of the diol intermediate. Note that both ozonolysis and the one-pot Lemieux–Johnson oxidative cleavage process of 8 led instead to methyl ketone 11 in a

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

• to the literature, a Sharpless dihydroxylation of benzyl tiglate (8) to form a chiral diol 9 was followed by a Parikh–Doering oxidation to give the corresponding product 10 in 62% yield (Scheme 4) [58][59]. Subsequent acryloylation in the presence of DMAP and hydroquinone gave the intramolecular