Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• a single hydroxylation step of β-carotene (6), but it requires two hydroxylation steps in plants [84]. In the crocin biosynthetic pathways, lycopene (5), β-carotene (6), and zeaxanthin (7) are cleaved by different CCDs to form crocetin dialdehyde (8). CsCCD2 from C. sativus could break the 7,8 and 7

• CsCCD2 belongs to a distinct branch within the CCD family. In vitro experiments confirmed that CsCCD2 catalyzed the cleavage of 7 between the 7,8- and 7',8'-double bonds, resulting in the formation of crocetin dialdehyde (8) and 3-OH-β-cyclocitral (9) [90]. Recently, Liang et al. designed a variant of

• enzyme activity was lower than CsCCD2 [2][92]. BoCCD4-3 from Bixa orellana was revealed to cleave various carotenoids, lycopene (5), β-carotene (6), and zeaxanthin (7), to form crocetin dialdehyde (8) by in vitro assay [93][94]. In contrast, CsCCD2, BdCCD4.1, and BdCCD4.3 could only cleave zeaxanthin (7

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• and forms an unstable intermediate that easily forms activated dialdehyde B. The amine 24 reacts with activated dialdehyde and provides the corresponding pyrrole 25 through the removal of water molecules. Smith and co-workers [65] reported a modified one-pot, two-step Clauson–Kaas procedure for the

• 2,5-DMTHF (2) in the presence of iodine under MW irradiation afford intermediate A, which is converted to dialdehyde B. Finally, N-substituted pyrroles 61 are produced by nucleophilic addition of amines with dialdehyde, followed by dehydration and aromatization steps (Scheme 29b). Jafari et al. [84

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

• ), where the eight-membered ring was accessed through a SmI2-mediated cyclization cascade reaction of a dialdehyde [69]. In this approach, an original way was proposed to form in a single step the tricyclic core of pleuromutilin (1) with a stereocontrol at the four contiguous stereocenters [69][70]. The

• dialdehyde was obtained from trans-dihydrocarvone (141) and treated early in the sequence (step 13/34) by SmI2. The authors assumed that the cascade reaction was initiated with the left-hand aldehyde ketyl formation 146 which further attacked the alkene and oriented the anti-5-exo-trig-cyclization toward (Z

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

• of an aldehyde resulting in a regioselective aldolization [29]. Thereafter, we hypothesized converting cyclopentadiene 6b into 2,5-cyclohexadienone 5 by a sequence involving the oxidation into dialdehyde 7 and treatment with pentan-3-one to enable sequential steps of aldolization and crotonization

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• . Alkylation of arenes with aromatic aldehydes in the presence of acetyl bromide and ZnBr2/SiO2. BF3·H2O-catalyzed hydroxyalkylation of arenes with aromatic dialdehyde 44. Bi(OTf)3-promoted Friedel–Crafts alkylation of triarylmethanes and aromatic acylals and of arenes and aromatic aldehydes. Reduction of

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• synthesized by Milde et al. (Scheme 11) [8]. The imidazole intermediates 61 were obtained by coupling iodoaniline (59) with the dialdehyde 60. Selective metalation of the imidazole ring and subsequent treatment with the phosphine gave the imidazolylphosphine ligands 62 and 63 (46–64%). The fast and clean

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• triazole containing dialdehyde and binaphthyl with dipyrromethene, followed by zinc metalation and subsequent reaction with MeI resulted in the synthesis of the two-component catalytic system 16 (Figure 13). Here, the cooperative effect of nucleophilic triazolium moieties, their counter ion near the

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• diversity in macrocycles. In this approach, two different bifunctional building blocks were combined: diacid/diisocyanide (Scheme 32). This approach also allows the combination of diacid/dialdehyde and dialdehyde/diisocyanide. Macrolactones 164 and 166 were readily obtained using readily available starting

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• the addition of a protecting step of the unstable key intermediate 4,5-dihydroisobenzofuran-5-ol. Oxidation and deprotection steps were also studied in order to provide an effective availability of these two dialdehyde compounds that may increase their future applications. Keywords: demethylation

• decided to go for anhydrous deprotection reaction, and in doing so, keeping the dialdehyde part untouched. Accordingly, hydrogen bromide was employed as a deprotection agent, as previously used by Borisenko et al. [23], to finally achieve the desired product 6 but in a very poor yield (5%). A second

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• ring-opened product 18 using an alternative path. The double bond in the norbornene nucleus in compound 17 was cleaved in the traditional way by treatment with OsO4/NaIO4 and the resulting dialdehyde on Wittig reaction provided the diene 18 in 66% yield in two steps. Amazingly when compound 18 was

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• the corresponding epoxide 110. Unfortunately, generation of epoxide was not realized (Scheme 16). Macrocycles To develop new synthetic strategies to various cyclophanes, we conceived a sequential usage of the SM coupling and RCM as key steps [48][49]. In this context, the required dialdehyde 113 (80

• %) was prepared via a SM coupling of the dibromo compound 112 with 4-formylphenylboronic acid (100). Treatment of dialdehyde 113 with allyl bromide (28) in the presence of indium powder furnished the RCM precursor 114. Under the influence of the G-II catalyst 2 RCM of diolefinic compound 114 was realized

• . Then, the cyclized product was subjected to the oxidation sequence with pyridinium chlorochromate (PCC) to generate cylophane derivative 115 in 75% yield (Scheme 17). Similarly, treatment of dialdehyde 113 with a freshly prepared Grignard reagent derived from 4-bromobut-1-ene (116) afforded dialkenyl

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• , contains a masked α,β-unsaturated 1,4-dialdehyde moiety, the presence of which has been proposed to be the cause of the feeding deterrent activity exhibited by the mollusc. We have found onchidal acts as an electrophile, reacting rapidly with the model nucleophile n-pentylamine forming diastereomeric

• model protein lysozyme, forming covalent adducts and leading to protein cross-linking. These results provide preliminary evidence supporting the molecular mechanism of biological activity exhibited by onchidal. Keywords: dialdehyde; lysozyme; mollusc; onchidal; pyrrole; Introduction More than 80

• terpenoid natural products containing the 1,4-dialdehyde moiety have been isolated from sources such as fungi, algae, sponges and molluscs [1]. Many of these natural products exhibit biological activity, ranging from anti-inflammatory to antimicrobial and antifeedant activities [1]. The prototypical

Coordination-driven self-assembly vs dynamic covalent chemistry: versatile methods for the synthesis of molecular metallarectangles

• Li-Li Ma,
• Jia-Qin Han,
• Wei-Guo Jia and
• Ying-Feng Han

Beilstein J. Org. Chem. 2018, 14, 2027–2034, doi:10.3762/bjoc.14.178

• ] condensation reactions of half-sandwich rhodium-based dialdehyde complex 2 with trans-4,4'-stilbenediamine (method B); (d) half-sandwich rhodium-based dialdehyde 2; (e) the product of self-assembly of organometallic clip 1, trans-4,4'-stilbenediamine and 4-formylpyridine in a one-pot procedure (method C

• ). Partial 1H NMR spectra (400 MHz, DMSO-d6, ppm) of (a) L2; (b) a sample of metallarectangle 3b obtained by coordination-driven self-assembly of organometallic clip 1 and L2 (method A); (c) a sample of metallarectangle 3b obtained by [4 + 4] condensation reactions of half-sandwich rhodium-based dialdehyde

• complex 2 with 1,5-diaminonaphthalene (method B); (d) half-sandwich rhodium-based dialdehyde 2; (e) the product of assembly of organometallic clip 1, 1,5-diaminonaphthalene and 4-formylpyridine in a one-pot procedure (method C). Calculated (bottom) and experimental (top) ESI-MS spectra of the

Cobalt–metalloid alloys for electrochemical oxidation of 5-hydroxymethylfurfural as an alternative anode reaction in lieu of oxygen evolution during water splitting

• Jonas Weidner,
• Stefan Barwe,
• Kirill Sliozberg,
• Stefan Piontek,
• Justus Masa,
• Ulf-Peter Apfel and
• Wolfgang Schuhmann

Beilstein J. Org. Chem. 2018, 14, 1436–1445, doi:10.3762/bjoc.14.121

• with oxidation of either the alcohol or the aldehyde leading to the dialdehyde 2,5-diformylfuran (DFF) or to 5-hydroxymethyl-2-furancarboxylic acid (HMFCA), respectively (Figure 4a). Subsequent oxidation of DFF and HMFCA leads to 5-formyl-2-furancarboxylic acid (FFCA) and finally to FDCA. The

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• reported the compound’s X-ray crystal structure. This transformation can also be achieved with MoOCl4 [7]. Dersch and Reichardt obtained the tetrafluoro derivative 1e in the attempted preparation of difluoromalonic dialdehyde (Scheme 1, reaction 5) [8], and Guseinov et al. reported the synthesis of the

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

• Felicia D’Andrea,
• Giorgio Catelani,
• Lorenzo Guazzelli and
• Venerando Pistarà

Beilstein J. Org. Chem. 2016, 12, 2343–2350, doi:10.3762/bjoc.12.227

• -promoted [28][29][30] pinacol coupling of dialdehyde derivatives). A strategy related to the latter approach relies on a base-promoted aldol condensation of aldohexos-5-uloses followed by reduction of the carbonyl group, as reported in the retrosynthetic Scheme 1. This method again uses sugars as starting

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• explore the selective Wittig mono-olefination of dialdehyde 5 readily accessible from the known 2,3;22,23-epoxysqualene (7) [28]. As depicted in Scheme 1, the synthetic sequence began with the treatment of squalene with two equivalents of NBS in a water/THF mixture. After separation of the bis-bromohydrin

• from the monoproduct, potassium carbonate treatment gave the expected diepoxide 7. Oxidative cleavage with periodic acid provided the corresponding dialdehyde 5 in 17% overall yield from squalene. The perdeuterated phosphonium salt 9 was obtained by simple condensation of commercially available 2

• -bromopropane-d7 (8) with triphenylphosphine [29]. To our surprise, condensation of dialdehyde 5 with one equivalent of the ylide 4 (9, n-BuLi, THF, −78 °C) did not afford any amount of the desired deuterated olefin but only polar material that could not be characterized. In an attempt to find more efficient

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• ] with two different dendrimeric alkyne scaffolds. Results and Discussion The “masked” dialdehyde intermediate 2 was easily synthesized in four steps and 80% overall yield from D-mannose without the need of any chromatographic purification, by following a slight modification of the published procedure

• Pd(OH)2/C in MeOH followed by reductive amination of the formed dialdehyde intermediate with 3-azidopropyl-1-amine [34] in the presence of NaBH3CN and AcOH allowed access to N-alkylated piperidine 4 in 67% yield (Scheme 2) [25]. With the key azido intermediate 4 in hands, we proceeded with the

• amination on aldehyde 2 allowed the synthesis of trihydroxypiperidines, among which the enantiomer of natural compound 1 and the N-alkylated piperidine 3. Synthesis of key azide intermediate 4 through the double reductive amination strategy from “masked” dialdehyde intermediate 2. Tetravalent and nonavalent

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• [7.2.0]undecane ring system 31 as found in xeniaphyllanes [3]. Finally, double C–H oxidation furnishes the β-hydroxy aldehyde 32 which can undergo a retro-aldol reaction with concomitant opening of the cyclobutane ring to form dialdehyde 33 as the common biogenetic precursor of xenicins, xeniolides and

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• interlocked systems and molecular switches [77][78]. Our longstanding interest in foldamers prompted us to explore the application of this noncovalent force for the generation of new, folded patterns. Thus, Lan Chen prepared polymers P31a and P31b from the corresponding dialdehyde and di(acylhydrazine

Design and synthesis of hybrid cyclophanes containing thiophene and indole units via Grignard reaction, Fischer indolization and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Mukesh E. Shirbhate

Beilstein J. Org. Chem. 2015, 11, 1514–1519, doi:10.3762/bjoc.11.165

• started with a Grignard addition reaction. In this context, commercially available thiophene-2,5-dicarbaldehyde (4) was reacted with the Grignard reagent [23] derived from 5-bromo-1-pentene to give diol 6 as a diastereomeric mixture (Scheme 1). Alternatively, the dialdehyde 4 can be prepared by using the

• heated to reflux until the brown colour disappeared. Then, 5-bromo-1-pentene (273 mg, 1.92 mmol) was added and the reaction mixture was stirred for 30 min. Next, thiophene 2,5-dialdehyde (4, 100 mg, 0.71 mmol) was added and the resulting mixture was stirred and heated at reflux for 3 h. After completion

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• , dibromide 83 was converted to bis-aldehyde 84. Finally, McMurry coupling of dialdehyde 84 provided the cyclophane derivative 85 (28%). Yamoto and co-workers have reported the synthesis of medium-sized cyclophanes, [2.n]metacyclophane-1,2-diols 86 and 87 by using the McMurry coupling as a key step (Figure 8

• -ol (110) generates the diyne product in quantitative yield. Next, the in situ prepared diyne was subjected to hydrogenation followed by oxidation with PCC which gave the dialdehyde 111 (85%). The pinacol coupling of the dialdehyde 111 in the presence of Sm2+ and HMPA generated the cyclophane 112 in a

• moderate yield. RCM of the diene derived from the dialdehyde 111 afforded the macrocyclic cyclophane 113 as a less strained product (Scheme 16). Sonogashira coupling: Wegner and co-workers [125] have reported the synthesis of cyclophanes 122a–c via Sonogoshira coupling [126] (Scheme 17). To this end, the

A hybrid electron donor comprising cyclopentadithiophene and dithiafulvenyl for dye-sensitized solar cells

• Gleb Sorohhov,
• Chenyi Yi,
• Michael Grätzel,
• Silvio Decurtins and
• Shi-Xia Liu

Beilstein J. Org. Chem. 2015, 11, 1052–1059, doi:10.3762/bjoc.11.118

• [20] of 4,5-bis(hexylthio)-1,3-dithiole-2-thione with the dialdehyde CPDT 3 [21] was successfully applied. The preparation of the latter was accomplished in 57% yield through the reaction of 4,4-dihexyl-4H-cyclopenta[2,1-b:3,4-b’]dithiophene [22] with oxalyl chloride in the presence of DMF. However

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• dialdehyde intermediates has been efficiently applied in recent years for the synthesis of a series of valuable organic molecules [45][46][47][48][49][50][51][52]. In particular, Davies and co-workers have utilized the oxidative ring opening of cyclic vicinal diols followed by ring closure for access to

• stereoisomers (determined on the basis of 1H NMR data) failed, but the mixture could be applied in the next ring-opening oxidation step, since it gave only one open-chain diformyl intermediate I2. Similarly to the cis isomer, this unstable dialdehyde intermediate was subjected without isolation to catalytic