Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• Sciences and Biotechnology, Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai, 200240, China 10.3762/bjoc.21.204 Abstract Herein, we report a concise chemoenzymatic synthesis of the cardenolide rhodexin A in 9 steps and the first protecting-group-free synthesis of its

• ; C–H hydroxylation; chemoenzymatic synthesis; Mukaiyama hydration; protecting-group-free synthesis; Introduction Cardiac glycosides (CGs) are widely distributed natural products, generated by plants and amphibians [1]. Structurally, they are composed of an aglycone-steroidal moiety, an unsaturated

• with high diastereoselectivity (dr = 14β/14α = 6.7:1), and the minor component 14-epi-sarmentogenin could be readily separated. Notably, our work represents the first protecting-group-free synthesis [34][35] of sarmentogenin in just 7 steps from 17-deoxycortisone. With the aglycone sarmentogenin (2) in

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• sarglamides A, C, D and E were established through a concise and protecting group-free approach, which was definitely inspired and utilized by the analysis of the biogenetic pathway of these natural products. Through this approach, a notable amount of natural products were made in one batch. The synthesis

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• atom efficiency, step and pot economies, decreased number of purification steps, or protecting-group-free synthesis. Multi-step domino [1][2] and one-pot [3] reactions represent a new powerful toolbox in organic synthesis to install molecular complexity economically and sustainably, starting from

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• of atom economy and protecting-group-free synthesis dominating the field of total synthesis. In this new era, total synthesis is moving towards natural efficacy by utilizing both the biosynthetic knowledge of divergent synthesis and the latest developments in radical chemistry. This contemporary

• protecting-group-free synthesis [13], are gradually drawing more and more the interest of organic chemists as a sustainable way to deliver structurally diverse chemical libraries for biological screening. The current review is focusing on selected examples utilizing a radical-based divergent total synthesis

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• future, such as protecting-group-free methodologies, peptide biosensors, and facile functionalizations within unexplored realms of complex peptides. Proposed reaction mechanism of C–H fluorination by a manganese porphyrin catalyst. Proposed mechanism of C–H radiofluorination. Proposed reaction mechanism

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• [27]) and coupling partners [28], great attention has been paid to a stereoselective glycosylation by sterically fixed glycosyl fluorides as glycosyl donors [29][30][31]. The enhanced stability of glycosyl fluorides has also allowed to develop a straightforward protecting-group-free strategy towards

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• [3 + 2] methylenecyclopentane annulations of olefins with methylenecyclopropanes. This regioselective, mild, and protecting group-free annulation requires only an equimolar amount of the reacting alkene and does not require an excess of the reacting alkene, unlike other methods [9]. Furthermore, the

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

• product 2-[18F]FPhe 46 in 43% yield, whereas under microwave irradiation a 34% yield was obtained. Under the optimized conditions, the enantiomeric purity was reported to be ≥94% ee [46] (Scheme 10). 1.3. Photooxidative cyanation of fluorinated benzylamine A convenient, protecting group-free, and

Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

• Thomas J. Cogswell,
• Craig S. Donald and
• Rodolfo Marquez

Beilstein J. Org. Chem. 2020, 16, 135–139, doi:10.3762/bjoc.16.15

• Zealand 10.3762/bjoc.16.15 Abstract A fast, protecting-group-free synthesis of dihydropyridinones has been developed. Starting from commercially available aldehydes, a novel one-pot amidoallylation gave access to diene compounds in good yields. Ring-closing metathesis conditions were then employed to

• produce the target dihydropyridinones efficiently and in high yields. Keywords: amidoallylation; aza-goniothalamin; dihydropyridinones; protecting-group-free; ring-closing metathesis; two-pot procedure; Introduction Six-membered nitrogen heterocycles are prevalent in many naturally occurring and

• conditions [27][28]. Ring-closing metathesis of diene 10 then proceeded in good yield (68%) to complete a fast and efficient, protecting-group-free, two-pot procedure for the racemic synthesis of aza-goniothalamin 1. Conclusion In summary, a two-pot, protecting-group-free procedure for the synthesis of

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

• were employed to successfully achieve Berchtold’s tetracyclic C-5,C-6 olefin intermediate 45 in only 7 steps with 8.1% overall yield in a protecting-group-free synthesis. However, we know the conversion of Berchtold’s C-5,C-6 tetracyclic olefin intermediate 45 to triptophenolide methyl ether (8) is a

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• moieties. Nonetheless, by taking advantage of the differential reactivity of the anomeric center, a selective activation at this position is possible. As a result, protecting group-free strategies to effect glycosylations are available thanks to the tremendous efforts of many research groups. In this

• linchpin for protecting-group-free glycosylation is an exploitation of the differential reactivity of the anomeric center. Two key features of the anomeric center provide this possibility. Firstly, the anomeric position of all unprotected monosaccharides is a reducing end (i.e., in equilibrium as an

• selective deprotonation of this hydroxy group over the others. This selective creation of a better nucleophile in the presence of the other protonated hydroxy groups can be regarded as an umpolung process. Despite this seeming difficulty, some protecting-group-free strategies to synthesize glycosides and

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• reductive amination to accomplish such a synthesis through a short protecting-group-free route and (c) the compatibility of the starting material and all reaction conditions to the aqueous media, here we present the aqueous semisynthesis of mono- and disaccharide glycamines obtained by hydrolysis and

• obtain C-glycofuranose-containing glycamines through a short, protecting-group-free and aqueous-based semisynthesis. Our present study also addressed the obstacles frequently faced in reductive amination of carbohydrates (such as byproduct accumulation and purification issues) and contributed to provide

• -group-free; reductive amination; Findings Agarose (1) is the term utilized to describe a type of galactose-containing polysaccharides biosynthesized by certain species of algae belonging to the division Rhodophyta (red seaweeds). It is a linear biopolymer constituted of the disaccharide repeating unit

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• organic synthesis, very recent examples have been selected and will be discussed here. In the context of green chemistry [11], protecting-group free organic synthesis has received particular attention in the last years, because of atom economy [12][13][14][15] and reduction of synthetic steps [16]. It has

• been demonstrated by Yoshida that protecting-group-free synthesis could be feasible using flash chemistry and microreactor technology [17][18]. Recently, Yoshida and co-workers developed flash methods for the generation of highly unstable carbamoyl anions, such as carbamoyllithium, using a flow

• Yoshida reported another remarkable finding on the use of protecting-group-free organolithium chemistry. In particular, the flash chemistry approach was exploited for generating benzyllithiums bearing aldehyde or ketone carbonyl groups [20]. This reaction could be problematic for two reasons: a) the

One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

• Gastón Silveira-Dorta,
• Sergio J. Álvarez-Méndez,
• Víctor S. Martín and
• José M. Padrón

Beilstein J. Org. Chem. 2016, 12, 957–962, doi:10.3762/bjoc.12.94

• and threonine derivatives. Keywords: amino acids; olefination; protecting group free; synthetic methods; Wittig reactions; Introduction Allylic amines have received significant attention because they represent a common scaffold in diverse biologically relevant compounds and natural products [1]. In

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• -aminothiazole peptidomimetics 127 in sufficient overall yields (5–13%). In a variation, the authors designed an ammonia-based Ugi reaction that avoids the use of protected amines (Scheme 38) [107]. It was shown that this protecting-group-free protocol tolerates a great variety of different isocyanides and also

A protecting group-free synthesis of the Colorado potato beetle pheromone

• Zhongtao Wu,
• Manuel Jäger,
• Jeffrey Buter and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2013, 9, 2374–2377, doi:10.3762/bjoc.9.273

• of glycosides (Scheme 1) [14] and expected that the approach might also be applicable in the synthesis of (S)-1. Triol 3, with vicinal primary, secondary, and tertiary hydroxy groups should be a suitable substrate for chemoselective oxidation with catalyst 2, enabling a protecting group-free

Study on the total synthesis of velbanamine: Chemoselective dioxygenation of alkenes with PIFA via a stop-and-flow strategy

• Huili Liu,
• Kuan Zheng,
• Xiang Lu,
• Xiaoxia Wang and
• Ran Hong

Beilstein J. Org. Chem. 2013, 9, 983–990, doi:10.3762/bjoc.9.113

• . Moreover, this approach also chemoselectively functionalizes terminal alkenes instead of internal ones. Substituted 5-hydroxymethyl-γ-lactones have been constructed in a protecting-group-free manner. The synthetic application in the efficient synthesis of velbanamine-type indole alkaloids as well as the

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• mL/min), with recovery of 15.6 g of starting material [79]. To process the same amount in batch at 65% conversion would require 120 individual 0.5 g scale reactions with no recovery of starting material. This FEP reactor was essential for the protecting-group-free synthesis of (±)-neostenine [80

meta-Oligoazobiphenyls – synthesis via site-selective Mills reaction and photochemical properties

• Raphael Reuter and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2012, 8, 877–883, doi:10.3762/bjoc.8.99

• example, biological settings. As a synthetic strategy it would be highly desirable to be able to build up the oligomer in a modular, protecting-group-free manner. In this respect, we planed a combination of the Mills reaction [27] with Suzuki cross-coupling, which we have successfully employed in previous