(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• are significantly increased compared with the parent compound. The observed aqueous solubilities of BCPs (+)-21 and (−)-21 were much higher than that of telmisartan. For the lomitapide isosteres (+)-22 and (−)-22, the solubility was different for each enantiomer; while 1,2-BCP (+)-22 showed increased

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• depends on the relative configuration of the ligand used; cis-configuration of ligand affords the nitroaldols with major enantiomer S- (up to 97% ee), whereas the application of ligands with trans-configuration led to nitroaldols with major R-enantiomer (up to 96% ee). The “proline-type” ligand IV was

• -enantiomer. A possible explanation of these results is illustrated in Figure 2, which shows plausible transition structures for the Henry reaction. Due to the Jahn–Teller effect, i.e., distortion of the octahedral Cu(II) complex forming four equatorial and two perpendicular coordination sites [18], the

• nitroaldols were obtained with an excess of S-enantiomer, likewise in catalysis by copper(II) complexes of ligands Ic, IIc and IIIb, as well as ligands based on pyridine-(imidazolidin-4-one) [5][6][7] owned the S-configuration at the imidazolidin-4-one ring (see Supporting Information File 1, part S5). Hence

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• products) [26]. HPLC: Phenomenex Lux Cellulose-3 column (3 mm, 250 × 4.6 mm), eluent CH3CN/H2O (0.1% formic acid) 40:60, isocratic mode; 0.6 mL min−1; UV detector 222 nm, 30 °C. The retention time for the (S)-enantiomer was 12.3 min, for the (R)-enantiomer 14.7 min. General procedure for recycling of the

• min−1; UV detector 265 nm, 35 °C. The retention time for the (S)-enantiomer was 27.2 min, for the (R)-enantiomer 29.1 min. General procedure for recycling of the lipophilic organocatalyst in the stereoselective Michael addition of the cyclohexyl derivative of Meldrum’s acid to 4-chloro-trans-β

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• concomitant deprotection of the nitrogen and the ester groups. The sample was found to have a negative optical rotation, thereby indicating that the major enantiomer present had S configuration [26]. This allowed to establish that the configuration of the major diastereomer present in (RS)-14b was (RS,S), and

Functional characterisation of twelve terpene synthases from actinobacteria

• Anuj K. Chhalodia,
• Houchao Xu,
• Georges B. Tabekoueng,
• Binbin Gu,
• Kizerbo A. Taizoumbe,
• Lukas Lauterbach and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1386–1398, doi:10.3762/bjoc.19.100

• = +95.9 (c 0.55, CH2Cl2) pointed to the same enantiomer as is known from the plants Pinus sibirica ([α]D20 = +118.4) and Torreya nucifera ([α]D18 = +118.6) [34], and from the fungus Xylobolus frustulatus ([α]D25 = +99.9 (c 0.6, CHCl3)) [35]. This finding is rather unusual, as more and more cases were

• by NMR spectroscopy confirmed the identity of the enzyme product α-cadinene (Table S3, Figures S13–S20, Supporting Information File 1). The optical rotation of [α]D25 = +60.0 (c 0.015, C6D6) indicated the opposite enantiomer as in the plant Humulus lupulus ([α]D24 = −62.4 (c 0.868, CHCl3)) [37

• ). The optical rotation of [α]D25 = –9.4 (c 0.64, CH2Cl2) pointed to the same enantiomer as in the plant Viguiera oblongifolia ([α]D24 = –8 (c 0.4, CHCl3)) [43]. A (−)-amorpha-4,11-diene synthase (ADS) is also known from Artemisia annua and catalyses the first committed step in the biosynthesis of

Correction: Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 1370–1371, doi:10.3762/bjoc.19.97

• theoretical ECD spectra of both enantiomers to determine the absolute configuration. By comparison of the recalculated and the experimental spectra, it became evident that in fact, the (3S,4S)-enantiomer rather than the (3R,4R)-enantiomer was obtained (Figure 2). Consequently, in the first paragraph of the

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

• alcohol functions of 4.5 were deprotected in acidic media to produce 3-O-octadecyl-sn-glycerol (4.6). The enantiomer of 4.6 was obtained from 4.4 by protecting the primary alcohol with a benzyl group to give 4.7. Then, the deprotection of the two alcohol functions with H2SO4 in water followed by the

• , both enantiomers were reported. For the control of the chirality in position 2 of glycerol, (S)-solketal (17.1) was used as starting material to prepare first the hexadecylglycerol (R)-17.2 which was converted to its enantiomer following a five-step sequence (Figure 17A). First, tritylation and

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• this helical aza-NG was achieved by introducing a chiral auxiliary reagent at the nitrogen site [40], and the racemization barrier of one enantiomer was measured as 26.2 kcal/mol by monitoring the changes of CD spectra at 60–80 °C. The synthesis started with the Diels−Alder reaction of 5H-dibenzo[b,f

• racemization was observed by heating the enantiomer for 1 hour at 120 °C. Except for [5]helicene, Narita and co-workers also reported [7]- or [9]helicene-containing chiral NGs [42]. As shown in Scheme 4, dibromo-functionalized 1,2,3,4-tetraphenylbenzene 32 was treated with DDQ and TfOH to produce dibromo 33 as

• Gibbs activation energy of enantiomer 53 for the racemization process was determined as 33.0 kcal mol−1 at 298 K. The CPL spectra of M-53 and P-53 showed an emission maximum at 560 nm with glum value of 2.3 × 10−4. Instead of helicene formation in the final Scholl-type ring formation step, Martín and co

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• corresponding R,R-iPrBox-ligand the second enantiomer, (R)-arylglycine 10l could be prepared with a similar yield and enantioselectivity. Conclusion In summary, we have reported a palladium-catalyzed enantioselective three-component reaction of aryltrifluoroborates, sulfonamides, and glyoxylic acid. This method

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• , MeOH); lit. −44 (c 0.05, MeOH)) [18], confirming the same absolute configuration these compounds should be derived from the same biosynthetic pathway. In addition, the ECD spectra of (5S,8R,9S,10R,14S)-1 and its enantiomer were calculated at the B3LYP functional using a TD–DFT method [19]. As

An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies

• Tharun K. Kotammagari,
• Sweta Misra,
• Sayantan Paul,
• Sunita Kunte,
• Rajesh G. Gonnade,
• Manas K. Santra and
• Asish K. Bhattacharya

Beilstein J. Org. Chem. 2023, 19, 204–211, doi:10.3762/bjoc.19.19

• configuration of each enantiomer was determined by single-crystal X-ray analysis. In addition, a one-pot synthesis of (±)-incarviditone has been achieved from rac-rengyolone by using KHMDS as a base. We have also assessed the anticancer activity of all the synthesized compounds in breast cancer cells

• 'S, 9'R (Scheme 6). After separation of individual enantiomers, we recorded the CD spectra of both enantiomers in MeOH. (−)-Incarvilleatone [(−)-1] shows a negative optical rotation and a negative Cotton effect in the CD spectrum whereas the other enantiomer (+)-incarvilleatone [(+)-1] showed a

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

• reprotonation at C-1 of 1, leading to four different stereoisomers of cation I, i.e., I1 with a trans-decalin skeleton, its enantiomer I2, I3 representing the cis-decalin skeleton, and its enantiomer I4 (Scheme 6A). In principle, the eudesmane skeleton can also be formed through cyclisations induced by

• ], Acritopappus prunifolius [79], Aniba riparia [80], Juniperus oxycedrus [81], and Laggera alata [82] has not been determined. The (−)-enantiomer of 11 with the structure as shown in Scheme 9C was reported from Cabralea cangerana ([α]D20 = –1.3, c 1.3, CDCl3) [83], Zanthoxylum naranjillo (no value specified) [84

• ], and Chiloscyphus polyanthos ([α]D = −3.0, c 2.41, CHCl3) [85]. The (+)-enantiomer of 11 is known from Cinnamomum camphora ([α]D25 = +1.79), representing the first isolated enantiomerically enriched material [86]. The low value of the optical rotation of 11 makes configurational assignments based on

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• Information File 1). The same enantiomer was isolated from the wood oil of Cryptomeria japonica [17]. Therefore, the enantiomer R-14 from the frogs is different to the plant compound. This finding may point to a biosynthesis of 14 by the frogs themselves or by associated microorganisms, although uptake from

• synthesis and characterization showed that this compound is the opposite enantiomer of 14 known from plants. This may indicate biosynthesis in the frog, but more work has to be performed to establish this. Furthermore, a short diversity-oriented synthesis based on the work of Taber and Gunn [13] enabled

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• used dihydrodithiin-scaffolding is tentatively indicated on the target structures 70–81 [62][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80]. D’Alonzo, Palumbo, Guaranga and co-workers also developed a de novo synthesis of the unnatural enantiomer of the iminosugar drug miglustat

• [81]. Miglustat is a biologically active analog of the natural product deoxynojirimycin, and its enantiomer also shows a promising profile in early biological activity studies. In future applications of 1,4-dithiane or -dithiin building blocks, the recently described zincation protocol by Knochel and

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• were only reported for the natural compound (nat-cholesterol, 1) and its enantiomer (ent-cholesterol, ent-1) (Figure 1) [3]. While 1 and ent-1 are characterized by hydroxy groups in β-position at C3, epicholesterol (epi-1) has an α-OH at C3. Diets of animal sources like red meat, liver, milk, and

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

• , requiring only two purification steps [77]. FGI of 146 led to (−)-enantiomer 147, which serves as the radical point od divergence of this plan. HAT-initiated transannular free-radical cyclization of (−)-enantiomer 147 according to Baran’s protocols [78] provided the benzyl-protected (−)-pseudocopsinine 148

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• irradiation. The resulting iodoaryl cation radical abstracts the hydrogen atom from the benzylic position to form a benzyl radical, whose bromination gives the racemic benzyl bromide. The second step takes place without the participation of light and leads to only one enantiomer due to the assistance of the

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• anticipated that the amide 5 could be hydrolyzed to give a single enantiomer of amine 4. However, we found that amide 5 was remarkably resistant to hydrolysis, even under forcing conditions. For example, no amide hydrolysis was observed in concentrated aqueous NaOH solution at reflux (with or without an

• silica gel resulted in extensive decomposition. Therefore, the crude imine was immediately hydrolyzed using aqueous citric acid [14], affording (−)-7-amino-7,8-dihydrobisabolene (4) as a single stereoisomer in 90% yield over the two steps. The enantiomer of 4 is itself a natural product with cytotoxic

• hydrolyzed under basic conditions (Scheme 2) to form the enantiomer of halichonic acid B ((−)-2). It is interesting to note that halichonic acid B exists exclusively as an open-chain 4-hydroxycarboxylic acid even though the corresponding γ-lactones typically form spontaneously. Indeed, no lactone formation

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• -syntheses that are required [1][2][3][4]. Additionally, whereas either enantiomer of BINOL is relatively inexpensive (109 $/mol), it is not the case with SPINOL (17,000 $/mol), and VAPOL is not commercially available. Although one could synthesize these precursors as well, this multistep synthesis is time

• time. Consequently, the availability of each CPA enantiomer requires significant synthetic efforts from the diphenol precursor. In order to address these issues, we became interested in exploring C1-symmetrical CPAs, in which the chirality resides exclusively at the phosphorus atom. For this

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

• diminished yield for 15 (70%), lowering the overall yield of TDD to 33% over eight steps. The major enantiomer of 4 obtained from this second route was identical to natural TDD (Figure 1D) which is thus S-configured, i.e., derived from ʟ-tryptophan. Moreover, the olefinic double bond in 4 is Z-configured as

• enantiomer can only lead to a chiral dimer that, if formed at all, may crystallise less efficiently. Bioactivity testing Previous reports have mentioned that TDD (4) exhibits no antibacterial activity, without providing information about the test organisms used [9]. For this reason, and because of the above

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• (+)-ximaocavernosin P [(+)-1]. Further, these isothiocyano-containing enantiomers were usually isolated as scalable mixture (where one enantiomer predominates) with an enantiomeric excess of ca. 80% [11]. In contrast, the two neutral cadinane-type enantiomers (4 and 5) were produced as racemic mixture (1:1 ratio

The stereochemical course of 2-methylisoborneol biosynthesis

• Binbin Gu,
• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82

• the native substrate 2-Me-GPP, seems to imply that the isomerization through suprafacial allylic transposition of diphosphate should result in the intermediate (S)-2-Me-LPP (Figure 1B), which would be the opposite enantiomer as suggested by Cane [23]. This prompted us to investigate whether (R)- or (S

• %) (structures are shown in Figure 2). Reproducibility of these results was demonstrated in triplicates. While these data showed that enantiomerically enriched (R)-2-Me-LPP is more efficiently converted into 1 than the enriched S enantiomer, the enantiomeric purity of the substrates was not sufficiently high to

• decide, if only one enantiomer of LPP serves as the precursor to 1. Purification of the enantiomers of 2-Me-LPP In order to obtain the enantiomers of 2-Me-LPP with high purity, the synthetically obtained enantiomerically enriched compounds 6a and 6b were purified by HPLC using a chiral stationary phase

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

• resolution of the latter and the conversion of the suitable enantiomer to the drug lumateperone is disclosed in our patent application. Structure of lumateperone. First synthetic route leading to lumateperone (1). Alternate synthesis of lumateperone. Alternate synthetic approaches leading to racemic

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• )-38, featuring the BINOL unit on the axle, does not allow for higher stereoselectivities (19% ee), but interestingly gives the other product enantiomer as the main product (see Figure 9). In 2016, Takata and co-workers reported a pyridine-based rotaxane catalyst for the O-acylative asymmetric