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

• induce a more bioactive compound, fluorine atoms were introduced by acetylation and benzoylation of -NH at 152. Spiro compounds 152–154 were easily afforded in 34–62% overall yields (Scheme 40). The compounds showed excellent coenzymatic effects towards cellobiase activity produced by Chaetomium

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

• Suzuki–Miyaura coupling with boronic ester 53 and O-acetylation furnished 54. The dienophile component, morachalcone A (44), was synthesized from phenol 55 in four steps including O-prenylation and subsequent Claisen rearrangement, aldol condensation with 56, and deprotection. The key chemo-enzymatic

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• acetylation of the ent-3ba' using acetic anhydride and DABCO, furnishes the desired product ent-3ba. Conclusion In summary, we have realized the Michael addition reaction of 4-unsubstituted pyrazolin-5-ones to α,β-unsaturated ketones under organocatalytic conditions. The developed protocol was efficiently

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• increase was observed upon closing due to the spatial proximity in the cavity between the two substrates. In contrast, the open tweezers showed a higher rate for the acetylation of meta and para substrates as a result of substrate inhibition of the closed cavity. These tweezers constitute a remarkable

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• , followed by in situ re-acetylation of the C2-amino group and C6-alcohol with acetic anhydride, resulting in the formation of disaccharide 4 in a one-pot fashion. The anomeric benzyl protecting group in disaccharide 4 was then removed via a Pd/C-catalyzed hydrogenation reaction, producing a mixture of α/β

Synthesis of the 3’-O-sulfated TF antigen with a TEG-N₃ linker for glycodendrimersomes preparation to study lectin binding

• Mark Reihill,
• Hanyue Ma,
• Dennis Bengtsson and
• Stefan Oscarson

Beilstein J. Org. Chem. 2024, 20, 173–180, doi:10.3762/bjoc.20.17

• , led to isolation of a mixture of 2 and a tin-related impurity (n-butyl chain evident by NMR). Acetylation of this material followed by flash chromatography proved ineffective in removing the unwanted entity. To overcome this problem, flash chromatography was performed before stirring with the ion

• following acetylation without purification of the intermediate, why the synthesis is high-yielding (20% overall yield) and easily scalable (9 g of protected disaccharide 7 and 1 gram of target 2 were synthesized). Experimental General methods All reactions containing air- and moisture-sensitive reagents

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

• derivative 2.6. The treatment of 2.6 with trimethylamine produced an ammonium salt. A treatment with silver carbonate was applied to remove any traces of bromide salts. Then, the secondary alcohol was deprotected by hydrogenolysis to produce 2.7 (lyso-PAF). Finally, the acetylation of the secondary alcohol

• oxidation with Br2 and hydrolysis, the bromoethyl phosphate 5.4. Finally, the quaternarization with trimethylamine produced 5.5 and the acetylation produced 5.6 PAF. The intermediate compounds like 6.2 (1-O-alkylglycerol) or the protected secondary alcohol 6.6, either as enantiopure or racemic forms, are

• the incorporation of the trityl group, which is reported with 42% yield. The next steps correspond to the adaptation of previously reported methods with the use of bromoethyl dichlorophosphate (10.5) as precursor of the phosphocholine polar head group. The last steps (debenzylation and acetylation

Two new lanostanoid glycosides isolated from a Kenyan polypore Fomitopsis carnea

• Winnie Chemutai Sum,
• Sherif S. Ebada,
• Didsanutda Gonkhom,
• Cony Decock,
• Rémy Bertrand Teponno,
• Josphat Clement Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2023, 19, 1161–1169, doi:10.3762/bjoc.19.84

• effects of compound 1 and related analogues could be realized by C-3 hydrolysis. In 2010, Liu et al. also demonstrated the major role played by changes at C-16 on antibacterial effects of F. pinicola steroids [33]. The acetylation at C-16 reduced the potency compared to the corresponding congener with a

Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles

• Deepak Singh,
• Shyamal Pramanik and
• Soumitra Maity

Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48

• ), light (entry 15) or acetylation agent (entry 16) failed to provide the desired product 4a, displaying the necessity of each component for developing the reaction. Substrate scope With suitable reaction conditions (Table 1, entry 12), we systematically investigated the scope of this acetoxymalonylation

• isolated, further confirming the involvement of a malonyl radical generated by the cleavage of the C–Br bond of 2a [28]. Next, an attempt was made to identify the key intermediate of the reaction (Scheme 3B). When compound 5 was subjected to the acetylation reaction individually with Zn(OAc)2 and AcOH

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

• combretastatin D-1 (1) in 23% overall yield after 16 steps. Later, the same authors performed the enantioselective synthesis of 1 in an attempt to review its absolute configuration [41]. Thus, acetylation of compound 2 followed by the use of Jacobsen’s catalyst [42] to perform the epoxidation of the double bond

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• -workers [19], through a sequence of reduction to the alcohol, acetylation and reduction with lithium in ammonia (Scheme 3A) [20], and its structure was unambiguously assigned by X-ray crystallography of a silver nitrate adduct [21]. From natural sources, the compound was first obtained from Humulus

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• . (7E,9Z)-Dodeca-7,9-dien-1-yl acetate (3), the sex pheromone of European grapevine moth (Lobesia botrana), was thus obtained at a 14 g scale, with an overall 85% yield for the one-pot sequence involving the iron-catalyzed cross coupling followed by acetylation with Ac2O (Scheme 4b) [21]. Illustrating

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• only. This is facilitated when using heterogeneous catalysts or immobilized enzymes that are retained in cartridge reactors. For instance, Paradisi and co-workers reported an N-acetylation approach to produce melatonin analogs, where the pure product is obtained in the organic phase after evaporation

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

• suitable starting material for the SmI2-promoted pinacol coupling, directed by the free hydroxy group, affording a complete selectivity in the formation of the 7-membered ring B. The synthesis of grayanotoxin III was then achieved by acetylation of the secondary alcohols, oxidative cleavage of the MOM

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• as the price of some reagents and relatively low yields. In this work, we describe a method using low-cost reactants, such as methyl tosylate and DIPEA, which provides moderate to high yields and is a reasonable alternative to the existing methods. The acetylation of compound 1 using standard

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• . Initially, 1-azido-3-nitrobenzene (c) was obtained from m-nitroaniline (a) (Scheme 1) with excellent yields (98%), as previously described [41]. The protection of the 3β-OH group of the triterpene skeleton was carried out by acetylation using acetic anhydride to prevent cleavage in acidic conditions, which

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

• stereoselective kinetic resolution of allenol 3 via lipase AK-catalyzed acetylation [15]. In this way, unaltered, (−)-hydroxyallene 3 could be separated from (+)-acetyl derivative 9 through standard column chromatography (Scheme 3). Enantiomeric excesses of (−)-3 and (+)-9 were determined by chiral HPLC analyses

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

• ][50][51][52][53][54], no systematic report of N-formylation and N-acetylation by ball milling has been reported yet. Here, we describe two complementary procedures to prepare formamides and acetamides, applied to primary and secondary aromatic and aliphatic amines. The methodologies directly involve

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• -butyloxycarbonyl (Boc)-protected threonine using bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-Cl) [14][15] and Hünig’s base to give 9. Cleavage of the Boc group with 5% TFA followed by basic treatment resulted in the cyclisation to the dioxopiperazine 10. Acetylation and subsequent treatment with LiClO4 and

• DBU is a common strategy for the dehydration of serine and threonine units in peptides [16], but unfortunately the acetylation of 10 failed. Interestingly, the direct treatment of 10 with LiClO4 and DBU under prolonged reaction times (3 days) resulted in the elimination of water. This reaction

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• . When acetic anhydride was employed as electrophile, besides the protonated product 136a, two different alkylated products 147 and 148 were formed depending on the reaction time. The 1-acetoxylvinylated and 3-hydroxybut-2-enoylated products 147 and 148 were obtained, respectively, through O-acetylation

• and C-acetylation followed by enolization of the first generated acetylated benzocyclohexadiene-fused γ-phosphinolactams 149. The results indicated that short reaction times favored O-acetylation, while long reaction times preferred C-acetylation (Scheme 25) [52]. They further investigated various α,β

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 method for the acetylation of isoamyl alcohol (9) catalyzed by Candida antarctica lipase B (Scheme 3) [26]. A biphasic system consisting of n-heptane and an aqueous buffer solution is used and efficiently mixed in a Corning AFRTM Low Flow reactor providing a fine dispersion of the reaction mixture

• min isoamyl acetate (10) is obtained in 59% yield according to GC analysis [26]. Related methods for the enzyme-catalyzed acetylation of isoamyl alcohol (9) have been developed utilizing biphasic systems, supercritical carbon dioxide as a solvent, or packed-bed reactors with immobilized enzymes [27

• layer is mixed with vinyl acetate (53) and pumped through a column reactor containing Candida antarctica lipase A. At 30 °C and with a residence time of 11 min, acetylation of cis-alcohol 52 is mediated. After distillation, cis-woody acetate 54 is obtained in 89% isolated yield (de > 99%) on a gram

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• 132 and the acetylation agent 133 (Figure 30) were reacted in the presence of the copper(I)-loaded rotor [Cu2(130)]2+ no reaction was detected. In contrast, the dimeric complex [Fe(Cu2(130))2]6+, formed after addition of iron(II) ions, offers two cavities each with two copper(I) ions to pre-bind both

• 132 and 133 at an optimal reaction distance. It was no surprise, that due to the increased local concentration, the acetylation 132 + 133 → 134 did rapidly take place. Similarly, the bigger dimeric nanoswitch [Fe(Cu2(131))2]6+ catalyzed the acetylation of the larger substrate 136 due to size-matching

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• (Scheme 21). Dobrinescu and co-workers studied, besides acetylation reactions, the hydroacetylation of menadione for the synthesis of diacetylated menadiol derivatives through heterogeneous catalysis [121]. The first methodology involved the reduction of menadione (10) to menadiol (14), with sodium

• dithionite, followed by hydroacetylation of 14 with acetic anhydride, using nanoscopic acidic hydroxylated metal fluorides MFn-x(OH)x (M = Mg, Al; n = 2, 3; x < 0.1) as catalysts. This type of catalysts has a huge acidic versatility, once they can behave as Brønsted or Lewis acids. The reductive acetylation

• of 10 occurred in two steps and at high selectivity conversion rates when using AlF3-57 and MgF2-71 (Scheme 22A). The second proposal explored the reductive acetylation reaction of menadione (10) with acetic anhydride catalyzed by gold(III) deposited on the qualified metallic fluorides. The

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• B (Figure 1) is a cyclic tetrapeptide with a rather unusual epoxyketone side chain and was found to be a strong inhibitor of histone deacetylases (HDACs) [4][5]. HDACs are nuclear isozymes that regulate gene transcription via a dynamic process of acetylation and deacetylation of lysine residues of

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• -glucofuranose following chemoenzymatic and chemical routes in 34–35% and 24–25% overall yields, respectively. The quantitative and diastereoselective acetylation of primary hydroxy over two secondary hydroxy groups present in the key nucleoside precursor was mediated with Lipozyme® TL IM in 2

• acetylation; Introduction In the last few decades, modification of nucleoside/nucleotide analogues has been a field of keen interest to researchers due to their therapeutic properties for treatment of cancer, viral and microbial infections [1][2][3][4][5][6][7][8][9]. The very first cytotoxic

• % overall yield starting from compound 11, respectively (Scheme 2). The use of lipase as biocatalyst was employed for the selective acetylation of the primary hydroxy group present in trihydroxy nucleosides 14a,b. This led to the screening of two different lipases, viz Candida antarctica lipase-B (CAL-B