Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• easily overoxidized to carboxylic acids. Over the past decades a variety of methods have been developed, utilizing toxic heavy metals such as pyridinium dichromate (PDC) [3][4][5] or manganese dioxide (Figure 1) [6][7]. Molecular oxygen [8] and peroxides [9][10] can also be used as inexpensive terminal

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• series of primary benzylic biphenyls and two secondary substrates by comparing to the pulsed technique (pDC) to the traditional direct current (DC) technique (Figure 43B and C). Under a constant potential (CP) regime no product was observed, but it was demonstrated that the introduction of a resting

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• . Reaction of 24 with pyridinium dichromate (PDC) in DMF solvent afforded the acid derivative 25. This derivative was converted to the key intermediate 20 by oxidative decarboxylation [33]. Han et al. [43] developed a method for the novel oxathiolane intermediate 2-(tert-butyldiphenylsilyloxy)methyl-5

• temperature, and oxidation with a mild oxidizing agent, PDC, provided 28. Using the reaction of lead tetraacetate with 28 via oxidative decarboxylation afforded oxathiolane acetate derivative 20a. The synthesis of a 1,3-oxathiolane precursor required for the preparation of 3TC (1) in four steps was reported

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• , indicating a mismatch between the chiral auxiliary and the stereocenter in this substrate. Concerning the oxidative cyclization reaction, pyridinium dichromate (PDC) provided low yields of expected lactam 77. Many oxidants were checked for this transformation to take place, and the Sarett reagent [CrO3·(C5H5

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• tetracyclic compound 56. Dihydroxylation of freshly prepared 56 with OsO4 and then selective tosylation afforded 57 in 39% yield over two steps. Exposure of 57 to DBU upon heating gave the elimination product 58, which was subjected to an oxidative rearrangement with PDC to give enone 59 in 68% yield. Copper

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• , dioxane/water; d) NaIO4, then NaOCl2, H2NSO3H; e) MeI, K2CO3, acetone; f) AcOH, H2O; g) NaOH, MeOH; h) PDC, DMF; i) CF3COOH, CH2Cl2; j) H2, 5% Pd/C, MeOH, H2O. Two-carbon homologation of the protected L-serine. Reagents and conditions: a) Fmoc-succinimide, Na2CO3, dioxane, H2O; b) (3-hydroxymethyl)-3

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• is an unusual cofactor in that, even without the enzyme, it can catalyze many of these reactions [2]. For example, the decarboxylation of pyruvate in water can be accomplished by ThDP, but when it is bound to the enzyme pyruvate decarboxylase (PDC), the decarboxylation rate is increased by 12 orders

• were used to identify the signature UV absorbances for the IP form of ThDP. These were then used to demonstrate the presence of IP on yeast PDC [15]. Subsequently, the IP form was shown to have a positive CD signal around 300–310 nm, while a negative peak around 320–330 nm, similar to that observed

• , computational studies have been used to investigate full reaction mechanisms of ThDP enzymes, including pyruvate decarboxylase (PDC) [25][26][27][28], benzoylformate decarboxylase (BFDC) [29][30], acetohydroxy acid synthase [24][31][32][33][34][35], pyruvate dehydrogenase (PDH) [36], benzaldehyde lyase [37

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• triple-negative breast cancer MDA-MB-468 cells. Keywords: drug targeting; neuropeptide Y; PDC; peptide–drug conjugate; targeted tumor therapy; tubugi; tubulysin A; Ugi reaction; Introduction Until recently, the medication of tumor diseases was primarily based on more or less unspecific

• , PDCs are smaller in size – which may improve tissue and cell permeability, allows a more flexible and cost-efficient production, and in many cases small peptides are less antigenic [16]. Generally, a useful PDC must exhibit at least four major skills that are all required for the selective and potent

• treatment of, for instance, cancer cells: (1) a sufficient in vivo half-life, ideally hours to days, to reach the diseased cells with a high portion of intact PDC; (2) a selective conjugate binding to a specific target molecule, e.g., a cell-surface receptor, that is characteristic for the diseased cells

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

• cyclization with the aid of HCl followed by pyridinium dichromate (PDC) oxidation (Scheme 8). Schmidt and co-workers [39] described an efficient route involving RCM and SM coupling towards the synthesis of 8-aryl-substituted coumarin 64, a natural product isolated from the plant Galipea panamensis. To this

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• , including important PDCs that have progressed to phase III clinical trials. Last, we address possible difficulties that may emerge during the synthesis of PDCs, as also report ways to overcome them. Keywords: bioconjugates; cancer; drug delivery; PDC; peptide; peptide–drug conjugate; side-products in PDCs

• as prodrugs, due to the covalent coupling of a peptide to a drug via specific linkers. The main building blocks of a simple PDC include a cytotoxic agent (drug), a tumor-homing peptide (navigating/targeting moiety) and a linker between them (Figure 2B). This class of prodrugs is continuously gaining

• conjugation with the therapeutic payload. The overall experimental procedure to synthesize a PDC is usually rapid and facile. Notably, the overall cost to produce a PDC, where an already approved drug can be selected and re-used from a pool of available cytotoxic agents, is much lower compared to the cost of

Preparation of Pickering emulsions through interfacial adsorption by soft cyclodextrin nanogels

• Shintaro Kawano,
• Toshiyuki Kida,
• Mitsuru Akashi,
• Hirofumi Sato,
• Motohiro Shizuma and
• Daisuke Ono

Beilstein J. Org. Chem. 2015, 11, 2355–2364, doi:10.3762/bjoc.11.257

• a good colloidal stability in water. Figure 2 shows the 1H NMR spectra of the DM-β-CD/PDI polymer and DM-β-CD. The peaks of the DM-β-CD and 1,4-phenylene dicarbamyl (PDC) segments are broadened due to the restricted movement of the network linkage of the polymer. The integral ratio of the peaks for

• the phenyl groups in PDC to the peaks of H1 protons of DM-β-CD indicates that the PDC/DM-β-CD ratio is two. The appearance of C=O stretching bands from urethane (1714 cm−1) in the FTIR spectrum (Supporting Information File 1, Figure S1) confirms that a urethane-crosslinked polymer is formed. In

Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate

• Amjid Iqbal,
• El-Habib Sahraoui and
• Finian J. Leeper

Beilstein J. Org. Chem. 2014, 10, 2580–2585, doi:10.3762/bjoc.10.270

• , involving gold(I)-catalysed cyclisation of an alkynyl alcohol to form the furan ring. The furan analogue of thiamine diphosphate (ThDP) was also made and tested for binding to and inhibition of pyruvate decarboxylase (PDC) from Zymomonas mobilis (overexpressed in E. coli with a N-terminal His-tag). It is a

• group with the thiazolium ring of ThDP acting as an electron sink during catalysis in order to stabilise what would otherwise be an acyl carbanion in the form of an enamine intermediate [2]. The catalytic cycle for pyruvate decarboxylase (PDC, a representative ThDP-dependent enzyme), first proposed by

• , which binds 25,000 times more strongly (Ki = 14 pM) than ThDP to PDC from Zymomonas mobilis (ZmPDC) and 500 times more strongly (Ki = 5 nM) to the E1 component of α-ketoglutarate dehydrogenase [10]. This extremely tight binding can be rationalised by the structural similarity between 2 and the ylid of

Reaction of selected carbohydrate aldehydes with benzylmagnesium halides: benzyl versus o-tolyl rearrangement

• Maroš Bella,
• Bohumil Steiner,
• Vratislav Langer and
• Miroslav Koóš

Beilstein J. Org. Chem. 2014, 10, 1942–1950, doi:10.3762/bjoc.10.202

• relative ratio of o-tolyl and benzyl isomers. Finally, for the separation of o-tolyl isomer from benzyl isomer, a mixture of all four chromatographically non-separable isomeric alcohols 4–7 was oxidised using PDC, thereby destroying the chiral center at C-5 position of the saccharide moiety, to afford a

• mixture of alcohols 4–7 (1.47 g, 5.0 mmol) in CH2Cl2 (25 mL) was added dropwise to a magnetically stirred solution of pyridinium dichromate (PDC, 2.45 g, 6.5 mmol) and acetic anhydride (1.3 mL) in CH2Cl2 (25 mL) under cooling in an ice-water bath followed by heating under reflux for 3 h. The greater part

• reaction steps (Grignard reaction and PDC oxidation) starting from 10 mmol of aldehyde 3 are summarised in Table 2. 8: colourless solid; mp 105–106 °C; +12 (c 1, MeOH); 1H NMR (600 MHz, CDCl3) δ 7.60–7.22 (m, 5H, Ph), 5.26 (d, J3,4 = 4.3 Hz, 1H, H-4), 5.12 (s, 1H, H-1), 4.99 (dd, J2,3 = 5.7 Hz, J3,4 = 4.3

Structure elucidation of female-specific volatiles released by the parasitoid wasp Trichogramma turkestanica (Hymenoptera: Trichogrammatidae)

• Armin Tröger,
• Teris A. van Beek,
• Martinus E. Huigens,
• Isabel M. M. S. Silva,
• Maarten A. Posthumus and
• Wittko Francke

Beilstein J. Org. Chem. 2014, 10, 767–773, doi:10.3762/bjoc.10.72

• , 10 h; c: p-TsCl, DMAP, TEA, DCM, −20 °C to rt, 12 h; d: (3-methylbutyl)magnesium bromide, CuI, THF, −90 °C to rt, 16 h; e: TBAF, THF, rt, 14 h; f: PDC, MS 4 Å, DCM, −20 °C, 90 min; g: (3-methylbut-2-en-1-yl)triphenylphosphonium bromide, n-BuLi, THF, −40 °C to rt 16 h; h: 1) NaH, THF, −20 °C to rt, 1

• ; b: 1) DIAD, TPP, THF, −20 °C, 30 min; 2) 3,5-DNBA, rt, 40 min; 3) 17, rt, 17 h; c: 2 N NaOH aq, THF/MeOH, rt, 45 min; d: MsCl, TEA, DCM, −80 °C, 2 h; e: n-propylmagnesium bromide, CuI, THF, −90 °C to rt, 48 h; f: p-TsOH, MeOH/THF/H2O, rt, 2 h; g: PDC, MS 4 Å, DCM, −20 °C, 90 min; h: [(E)-1-methylbut

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

• Nicole Zimmermann,
• Robert Hilgraf,
• Lutz Lehmann,
• Daniel Ibarra and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140

• %); c) LiAlH4, Et2O (82%); d) Ac2O, pyridine, rt (91%); e) B2H6, 2-methyl-2-butene, 0 °C, THF, NaOH, H2O2 (66%). Synthesis of trans,trans-substituted dihydronepetalactone b. Reaction conditions: a) TBDMSCl, imidazole, DMF, 0 °C (99%); b) KOH, MeOH, 0 °C (87%); c) PDC, MS, CH2Cl2, 0 °C to rt (61%); d

Microphotochemistry: 4,4'-Dimethoxybenzophenone mediated photodecarboxylation reactions involving phthalimides

• Oksana Shvydkiv,
• Kieran Nolan and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2011, 7, 1055–1063, doi:10.3762/bjoc.7.121

• [20][21][22][23] and specialized micro-photoreactors for laboratory- to technical-scale synthesis have been developed [24][25][26]. We have recently reported on acetone-sensitized photodecarboxylation (PDC) reactions of phthalimides in a commercially available microreactor [27]. The photochemistry of

• transformations have also been realized on a semi-technical scale using an advanced falling-film batch reactor equipped with a 308 nm excimer light source [35][36]. However, the established PDC protocol utilizes UVB light for the activation step (direct or acetone sensitized), thus limiting the desired future

Oxidative allylic rearrangement of cycloalkenols: Formal total synthesis of enantiomerically pure trisporic acid B

• Silke Dubberke,
• Muhammad Abbas and
• Bernhard Westermann

Beilstein J. Org. Chem. 2011, 7, 421–425, doi:10.3762/bjoc.7.54

• the synthesis of natural occurring terpenes, i. a., trisporic acid and its derivatives. An advanced building block has been synthesized in a short reaction sequence, which involves an oxidative allylic rearrangement initiated by pyridinium dichromate (PDC) as the key step. Keywords: enzymatic

• . However, the configuration at the newly created stereogenic centre need not be determined since it is destroyed in the next step, the PDC-catalyzed rearrangement to (+)-7. After 7 h, no starting material was detected by TLC, allowing the isolation of the desired cyclohexenone 7 in 91% yield. Although

• (18), 131 (40), 107 (85), 91 (28), 79 (100); Anal. Calcd for C12H16O3 (208.3): C, 69.21; H, 7.74. Found: C, 69.05; H, 7.91. Methyl (+)-(1R)-2-ethynyl-1,3-dimethyl-4-oxocyclohex-2-ene-1-carboxylate (7). PDC (0.72 g, 1.90 mmol) was added to a solution of 6 (0.20 g, 0.90 mmol) in abs CH2Cl2 (5 mL) in the

CuCl-catalyzed aerobic oxidation of 2,3-allenols to 1,2-allenic ketones with 1:1 combination of phenanthroline and bipyridine as ligands

• Shuxu Gao,
• Yu Liu and
• Shengming Ma

Beilstein J. Org. Chem. 2011, 7, 396–403, doi:10.3762/bjoc.7.51

• by Markó et al., the yields are relatively lower. Keywords: allenic ketone; allenol; Cu(I) catalyst; oxidation; Introduction The oxidation of alcohols is one of many fundamental reactions in organic synthesis [1][2]. Usually, stoichiometric oxidants such as MnO2 [3], PCC [4], PDC [4], etc. were

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48