New synthesis of a late-stage tetracyclic key intermediate of lumateperone

• Mátyás Milen,
• Bálint Nyulasi,
• Tamás Nagy,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2022, 18, 653–659, doi:10.3762/bjoc.18.66

• chiral chromatography. Later, alternate syntheses of lumateperone were described, also by the researchers of the originator company [8][9][10] (Scheme 2). The reaction of (2-bromophenyl)hydrazine (12) with 4-piperidone monohydrate hydrochloride (13) gave pyrido[4,3-b]indole congener 14, which was reduced

Trichloroacetic acid fueled practical amine purifications

• Aleena Thomas,
• Baptiste Gasch,
• Enzo Olivieri and
• Adrien Quintard

Beilstein J. Org. Chem. 2022, 18, 225–231, doi:10.3762/bjoc.18.26

• % yield. Bulky 2,2,6,6-tetramethyl-4-piperidone could also be isolated from naphthalene in 94% yield through this approach (Table 3, entry 11). Other heterocyclic amines such as acridine or 1,2-dimethylimidazole could also be isolated with success in 53–65% yields (Table 3, entries 12 and 13). Of

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• of aldimine and ketoimine substrates under mild conditions [18]. Early studies reported a positive effect of sonication on the classical aminocyanation procedures. The reaction rate of the classical Strecker reaction using cyanide salts, amines and aromatic carbonyl derivatives [19] or piperidone [20

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• the work of Feringa and co-workers, the methylation reaction using Me2Zn resulted in a low yield of 44% due to the difficult purification of the crude product [15]. However, the same authors showed later that the copper-catalysed ACA of Me3Al to Boc-protected 4-piperidone can be used as a key step in

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• components in the outcome of the multicomponent coupling reaction. Similarly, the use of piperidone as the ketone component proved to work only when the amino group was protected as Boc, whereas the N-methyl derivative did not proceed to the coupling product (Table 1, entries 10 and 9, respectively). Indeed

• , the Boc-piperidone furnished the corresponding spirocyclopentenone derivatives upon changing both the aromatic alkyne or the acylating agent (Table 1, entries 10–12). When the Boc group was replaced with the tosyl one as the N-substituent, such chemical moiety proved to impair the subsequent Pauson

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• prochiral precursor 1-Boc-3-piperidone using immobilized ω-transaminases (TAs-IMB), isopropylamine as amine donor and pyridoxal-5’-phosphate (PLP) as cofactor is described. Compared to other methods, the present approach affords the target compound in just one step with high yield and high enantiomeric

• described [25]. However, the enzyme used in this study is not commercially available and no enantioselectivity of the reaction has been reported. Herein, we describe the use of several immobilized ω-transaminases in the asymmetric transamination of the selected substrate 1-Boc-3-piperidone. Selected

• mM, pH 7.5) containing isopropylamine (1.1 M), TA-IMB enzyme (200 mg) and PLP (1.4 mM) were added. The mixture was stirred at 35 °C and 550 rpm for 5 minutes, and then a preheated solution (35 °C) of 1-Boc-3-piperidone (1, 0.26 mmol, 45 mM) in DMSO (750 μL, 13% v/v) was added. The reaction was

Investigation of the role of stereoelectronic effects in the conformation of piperidones by NMR spectroscopy and X-ray diffraction

• Cesar Garcias-Morales,
• David Ortegón-Reyna and
• Armando Ariza-Castolo

Beilstein J. Org. Chem. 2015, 11, 1973–1984, doi:10.3762/bjoc.11.213

• –H(7)eq), a type of hyperconjugative interaction. Keywords: NMR spectroscopy; piperidone; spin–spin coupling constant; stereoelectronic effect; X-ray diffraction structure; Introduction Stereoelectronic effects have attracted the attention of many researchers with an interest in organic chemistry

• -nitrobenzaldehyde, and 2,6-dimethycyclohexanone for 8. The proposed reaction mechanism for piperidone formation is through an aldimine, which is formed by the reaction between an aldehyde and ammonium acetate. The aldimine is then attacked by a keto–enol to form a β-aminocarbonyl, which reacts with another molecule

• of aldehyde to form a second aldimine. Finally, 6-endo-enol-endo intramolecular cyclization leads to piperidone formation (Scheme 2) [58][59]. Structural and conformational analysis of piperidones 1–8 by NMR and X-ray diffraction Solution characterization of 1–8 was performed by 1H and 13C NMR, and

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• tryptophan and dopamine as precursors of pyridoacridines. Thus, formaldehyde and amino acids are responsible for the thiazole, piperidone, oxathiolane and thiomorpholinone rings found in pyridoacridines structures. Biological activity The biological activity of pyridoacridines, including both natural and

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• linker or in order to improve the drugs pharmacokinetic profile (increased solubility under physiological conditions and reduced logD value). Such heterocyclic systems are often disubstituted at the 1,2- or 1,4-positions resulting in easy access from the corresponding pyridone or piperidone precursors

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• stereospecifically the corresponding piperidone 4 in 80% yield. Subsequent bromination with CBr4 in the presence of PPh3 (Appel reaction) gave 5 in 84% yield. Finally, deprotection with 1 M SnCl4 in dichloromethane then neutralization by using K2CO3 afforded the final product (−)-epimyritine in a 80% yield. N-Cbz

Determination of the relative configuration of tropinone and granatanone aldols by using TBDMS ethers

• Ryszard Lazny,
• Aneta Nodzewska,
• Katarzyna Sidorowicz and
• Przemyslaw Kalicki

Beilstein J. Org. Chem. 2012, 8, 1877–1883, doi:10.3762/bjoc.8.216

• . Usually the vicinal coupling constants for syn and anti isomers differ enough to allow for configuration assignment [23] (e.g., aldols of cyclic ketones such as piperidone and cyclohexanone fall within the following typical ranges: syn: ca. 2–3 Hz, anti: ca. 7–9 Hz). In principle the new product could

Synthesis of 5-oxyquinoline derivatives for reversal of multidrug resistance

• Torsten Dittrich,
• Nils Hanekop,
• Nacera Infed,
• Lutz Schmitt and
• Manfred Braun

Beilstein J. Org. Chem. 2012, 8, 1700–1704, doi:10.3762/bjoc.8.193

• multidrug efflux pumps. Twelve 5-oxyisoquinoline derivatives, which are analogues of zosuquidar wherein the dibenzosuberyl-piperazine moiety is replaced by either a diarylaminopiperidine or a piperidone-derived acetal or thioacetal group, have been synthesized as pure enantiomers. Their inhibitory power has

• purification in the coupling reaction with epoxide (R)-16. The spirocyclic compounds 6c–13c were obtained by standard acid-catalyzed reaction with the corresponding diols for the formation of acetals 6c–12c and propanedithiol for 13c, starting from N-acetyl-4-piperidone. Basic hydrolysis was found to be

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• proteases [7]. Like microcystins, these peptides are frequently produced by bloom-forming freshwater cyanobacteria. The signature of this group is the unusual 3-amino-6-hydroxy-2-piperidone moiety (Ahp). The corresponding NRPS assembly line consists of seven modules [25]. Unique features include an

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

Synthesis of a novel analogue of DPP-4 inhibitor Alogliptin: Introduction of a spirocyclic moiety on the piperidine ring

• Arumugam Kodimuthali,
• Padala Lakshmi Prasunamba and
• Manojit Pal

Beilstein J. Org. Chem. 2010, 6, No. 71, doi:10.3762/bjoc.6.71

• not common. Initially, we attempted to synthesize the compound 9a from N-Boc protected piperidone 9b (PG = Boc) by the reported method [11] based on C-alkylation. Surprisingly, introduction of a cyclopropyl group at the position α to the piperidine carbonyl group with 2-chloroethyl dimethyl sulphonium

A convenient allylsilane- N-acyliminium route toward indolizidine and quinolizidine alkaloids

• Roland Remuson

Beilstein J. Org. Chem. 2007, 3, No. 32, doi:10.1186/1860-5397-3-32

•  11) to obtain quinolizidines whose conformation should not be distorted by the junction with the piperidone ring. Lactams 42a and 42b were reduced with lithium aluminium hydride to give methylenquinolizidines 44a and 44b in 92% and 78% yields respectively. Osmium tetroxide catalysed periodate

Flexible synthetic routes to poison- frog alkaloids of the 5,8-disubstituted indolizidine- class I: synthesis of common lactam chiral building blocks and application to the synthesis of (-)-203A, (-)-205A, and (-)-219F

• Naoki Toyooka,
• Dejun Zhou,
• Hideo Nemoto,
• H. Martin Garraffo,
• Thomas F. Spande and
• John W. Daly

Beilstein J. Org. Chem. 2007, 3, No. 29, doi:10.1186/1860-5397-3-29

• protected hydroxymethyl side-chain (Figure 2). The synthesis began with the known piperidone 3, [15] which was treated with n-BuLi and then CbzCl to provide the Cbz-urethane 4. Treatment of 4 with LiHMDS followed by 2-[N,N-bis(trifluoromethylsulfonyl)amino]-5-chloropyridine (Comins' reagent) [16] gave the

Diastereoselective synthesis of some novel benzopyranopyridine derivatives

• Pradeep K. Mohakhud,
• Sujeet M. R. Kumar,
• Vasanth M. R. Kumar,
• Ravi M. R. Kumar,
• Moses D. R. Babu,
• Vyas D. R. K and
• Om D. R. Reddy

Beilstein J. Org. Chem. 2006, 2, No. 25, doi:10.1186/1860-5397-2-25

• hydrogenolysis of 5a (Scheme 1). The reaction mechanism is suggested to follow a ketal deprotection sequence to arrive at the 4-piperidone derivative, which is protonated and reacts with the aromatic ring to afford the six member heterocycle. Deprotonation restores the aromatic ring and subsequent elimination of

Methods for the synthesis of polyhydroxylated piperidines by diastereoselective dihydroxylation: Exploitation in the two-directional synthesis of aza-C-linked disaccharide derivatives

• Andrew Kennedy,
• Adam Nelson and
• Alexis Perry

Beilstein J. Org. Chem. 2005, 1, No. 2, doi:10.1186/1860-5397-1-2

• rings, the sense of induction was different in each case. Presumably, the steric demands of the heteroatoms (N-tosyl and O) control the reactive conformation of the heterocycles. The more sterically demanding N-tosyl group forces the piperidone rings to adopt 1,2,6-tri-pseudo-axial conformations:[40