Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• obtained as pure and fully characterized compounds, namely by chiroptical methods. It should be mentioned that previous studies on hydnocarpin D failed to determine its absolute configuration. In 1973 Ranganathan and Seshadri isolated hydnocarpin D from H. wightiana for the first time and determined the

• stereochemistry of the substituents at C-10 and C-11 [12]. However, neither in this nor in later papers on hydnocarpin D the absolute configuration had been properly established. Also Guz et al. denote their compound as (±)-hydnocarpin D, which means that no optically pure compound was obtained [14]. The

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• -ketoesters 26a–f reacted with the substituted indoles 2 in the presence of ent-4 to achieve the corresponding adducts 27 with good yields and enantioselectivities (up to 88% yield, up to 76% ee) (Scheme 11). Although the absolute configuration was unknown at that point, the authors envisioned a plausible

• would coordinate and direct the hydrazone 28 to the Re face of the esters 26 in order to afford the absolute configuration found in the final products 29 of this process (Figure 7). Another example of the bifunctional action of the indanol-based thiourea 4 was reported by Sibi’s group. There, 100 mol

• framework. In this case, a pyrazole moiety presents additional H-bond acceptor sites. These could play an important role in fixing the substrate to the catalyst and favoring a more rigid transition state (TS11) and thus leading to better selectivity (Scheme 12). The absolute configuration is only given for

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• same stereochemistry as linezolid, though in some cases the absolute configuration can shift from S to R. Candidates 13/14 and 15/16 are diastereomers. Guests 8, 9, 10 and 19 were included in our test set in order to probe if different halogen atoms (B ring) influence the affinity. It is known that

Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors

• Ming-Liang Zhang,
• Deng-Feng Yue,
• Zhen-Hua Wang,
• Yuan Luo,
• Xiao-Ying Xu,
• Xiao-Mei Zhang and
• Wei-Cheng Yuan

Beilstein J. Org. Chem. 2016, 12, 295–300, doi:10.3762/bjoc.12.31

• ). The absolute configuration of the major isomer 4i was unambiguously determined to be S by single-crystal X-ray analysis (Figure 1) [38]. The configurations of the other products were assigned by analogy. On the basis of our experimental results and the related reports about the bifunctional activation

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• agent stereoisomers’ absolute configuration of the phosphorus atom was not firmly established. Thus, the van Hooidonk and Breebaart’s work dating from 1970, it is highly probable that they did not attributed the correct absolute configurations to the enantiomers of sarin, which means that the (S

• ]. They reported a stereospecific hydrolysis of soman with α-, β- and γ-CDs depending on the absolute configuration of its phosphorus atom. Indeed, more stable inclusion complexes are observed with the P(S)-stereoisomers of soman, but the degradation of the P(R)-stereoisomers remains strongly faster

• contradiction with the hydrolysis rates of soman previously by Désiré and Saint André [68][70], we can again raise a doubt about the validity of the assigned absolute configurations. Indeed, they reported a faster degradation of the two P(−)-diastereoisomers whose absolute configuration of the phosphorus atom

Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

• Jochen Kraft,
• Martin Golkowski and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 166–171, doi:10.3762/bjoc.12.18

• . The absolute configuration was assigned by comparison of the optical rotation values with literature data [29] which are based on the chemical correlation method leading to (+)-(S)-2-phenylsuccinate [30] and by X-ray structure determination of (R,E)-3,5-diphenylpent-4-enyl camphor-10-sulfonate [31

• ]. Thus, a positive optical rotation value refers to the (R)-enantiomer, whereas a negative value belongs to the (S)-enantiomer. In addition, the absolute configuration was independently determined by 1H NMR in the presence of the optically active NMR shift reagent (+)-Eu(hfc)3 [29]. All synthesized

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• , alkyl, and trimethylsilyl substituents result in 90–98% ee. The synthetic utility of these products, as well as their absolute configuration, was demonstrated by their reduction to the natural products (+)-galipinine, (+)-cuspareine, and (−)-angustureine. Additions to oxocarbenium ions Similar to the

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• also suggested that the SO2 moiety of benzothiadiazine catalyst would interact with the N-methyl substituent of the substrate by a non-classical hydrogen-bonding [39], improving the catalytic activities (see Supporting Information File 1 for details). The absolute configuration of 5 and 6 were assigned

Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones

• Antonia Di Mola,
• Maximilian Tiffner,
• Francesco Scorzelli,
• Laura Palombi,
• Rosanna Filosa,
• Paolo De Caprariis,
• Mario Waser and
• Antonio Massa

Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279

• to obtain both the enantiomers of chiral bioactive compounds. In this case, we focused on (R,R)-8a, which afforded the required (S)-7 (the absolute configuration has been previously determined by vibrational circular dichroism) [31]. Asymmetric synthesis of 9 by decarboxylation of (S)-7 Although

• a faster process and 7 or 10 have never been recovered. Since the decarboxylation does not directly affect the stereocenter, we can confidently assign the absolute configuration of (−)-9 as (S). Asymmetric synthesis of bioactive isoindolinones Inspired by well-known synthetic routes of racemic

Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality

• Jose I. Martínez,
• Uxue Uria,
• Maria Muñiz,
• Efraím Reyes,
• Luisa Carrillo and
• Jose L. Vicario

Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277

• nitroalkenes were not suitable substrates for the reaction, probably due to their tendency to polymerize under the reaction conditions. The absolute configuration was determined by X-ray analysis of products anti-3a and syn-3o for which suitable crystals could be obtained (Figure 1). The crystallographic

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• mechanism. An interesting feeding experiment was performed for the elucidation of both absolute configuration and biosynthesis of the polyketid alkaloid coelimycin P1 (8, Scheme 2). The compound was isolated from Streptomyces coelicolor M145 after genetically engineered increase of the metabolic flux and is

• incorporated into 8, showing the direct biosynthetic relationship of the amino acid derivative and indicating that the addition of N-acetylcysteine might not be catalyzed by an enzyme. Exploiting the only stereocenter of 8 being located in the incorporated residue, also the absolute configuration of 8 could be

• of NRPS products using isotopic labelings was recently developed by Bode and co-workers [36]. The method is designed to investigate the absolute configuration of the amino acid building blocks without hydrolysing the NRPS product, can be performed on minute amounts of material, and was first applied

Bromotyrosine-derived alkaloids from the Caribbean sponge Aplysina lacunosa

• Qun Göthel,
• Thanchanok Sirirak and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2334–2342, doi:10.3762/bjoc.11.254

• same side of the molecule. The absolute configuration of compound 1 was investigated by CD spectroscopy. The CD spectrum of 1 showed positive Cotton effects (λmax 248, Δε +5.16, λmax 285, Δε +4.58) with the same sign and magnitude as observed for (+)-aerothionin (11) [25][34][35]. Thus, the absolute

• configuration of spiroisoxazoline moieties were assigned as 1,1´-(R),6,6´-(S) (Figure 1). The absolute configuration of C-19 was assigned as 19-(R) according to NOE data which is in agreement with the proposed configuration by Molinski and co-workers [34][36]. The configuration of C-19 of fistularin-3 (5) was

• ) and 3.61 (C-7) as well as between 6.56 (H-6) and 3.17 (H-7) suggesting a trans-hydroxyspiroisoxazoline ring similar to compound 1. An NOE was also observed between δH 5.72 (11-OH) and 1-OH indicating the same planar alignment of both hydroxy groups. The absolute configuration of spiroisoxazoline

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• (+)-β-hydroxyhernadulcin isomer (Figure 1), which has been described as a sweetener [39]. Intrigued by the behavior of 3a we prepared the epimer 3d ([α]D −107° (c 1.2, CHCl3) vs lit. [8] [α]D −118.4° (c 0.5, CHCl3)) by the acid catalyzed racemization of C(6) stereogenic center. Remarkably, the absolute

• configuration at this stereocenter plays in important role, since 3d resulted pungent cool and bitter. Conclusion We improved the synthesis of (+)-hernadulcin on a multigram scale, and we have accomplished the first total synthesis of peroxylippidulcine A and lippidulcines A, B and C, confirming their absolute

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• Dactylospongia [24] and has significantly lower cytotoxicity. The absolute configuration of the natural material is not firmly established due to discrepancies in optical rotation values between natural and synthetic samples [25]. Zampanolide and dactylolide have engendered world-wide interest from the synthetic

The simple production of nonsymmetric quaterpyridines through Kröhnke pyridine synthesis

• Isabelle Sasaki,
• Jean-Claude Daran and
• Gérard Commenges

Beilstein J. Org. Chem. 2015, 11, 1781–1785, doi:10.3762/bjoc.11.193

• of 3.425(1) Å, resulting in a slippage of 1.54 Å. The absolute configuration is established by the occurrence of the known chirality of the starting material as (−)-(1R,5S)-myrtenal was used. Crystals of complex 9 were obtained by slow evaporation of a solution of the compound with

• distorted, square planar environment. The PtN4 framework is nearly planar with the largest deviations being −0.008(4) Å at the Pt atom. However, to accommodate the tetracoordination, the N-Pt-N angles range from 80.3(3)° to 116.8(3)°. Because of the presence of the Pt atom, the absolute configuration can be

Towards inhibitors of glycosyltransferases: A novel approach to the synthesis of 3-acetamido-3-deoxy-D-psicofuranose derivatives

• Maroš Bella,
• Miroslav Koóš and
• Chun-Hung Lin

Beilstein J. Org. Chem. 2015, 11, 1547–1552, doi:10.3762/bjoc.11.170

• (Table 2) are indicative of OT1 conformation (O2TC6, twisted on O2–C6, C6-exo, O2-endo). The absolute configuration at chiral atoms C2, C3, and C4 of the O1–C1–C2–C3–C4 furanose ring (Figure 2) was assigned on the basis of the known arrangement in analogous D-psicofuranose derivatives. The α-D

The enantioselective synthesis of (S)-(+)-mianserin and (S)-(+)-epinastine

• Piotr Roszkowski,
• Jan. K. Maurin and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2015, 11, 1509–1513, doi:10.3762/bjoc.11.164

• solubility in a hexane/2-propanol mixture. The absolute configuration of amine (S)-7 obtained by reduction of 6 using (R,R)-11 as catalyst was confirmed by X-ray analysis (Figure 3). Subsequently, the synthetic procedure developed by us for aptazepine was applied [8]. Amide 8 was obtained in 94% yield by

Chiroptical properties of 1,3-diphenylallene-anchored tetrathiafulvalene and its polymer synthesis

• Masashi Hasegawa,
• Junta Endo,
• Seiya Iwata,
• Toshiaki Shimasaki and
• Yasuhiro Mazaki

Beilstein J. Org. Chem. 2015, 11, 972–979, doi:10.3762/bjoc.11.109

• consistent with the hypothesis from the chiral exciton coupling method. To solidify the absolute configuration, the synthesis of (R)-3 from (R)-9 was carried out separately, and the ECD spectrum of the product from (R)-3 was in complete accord with that of (−)-9. Therefore, the absolute configuration of

• intensive Cotton effects at 318 nm (λfirst) and 254 nm (λsecond), together with a weak ellipticity in the range of ca. 360–450 nm. The shape of the trend line of PTDPA is similar to that of 3 with the same absolute configuration at the allenic moiety except for the small blue shift of the λsecond value of

First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• means of the assignment of the absolute configuration of the resolved enantiopure alcohol (S)-(+)-5 determined by a modified Mosher’s methodology, and was unambiguously confirmed by X-ray diffraction analysis. Optically active intermediates (S)-(+)-5 and (R)-(−)-7 achieved in this manner were

• scale” and ready-to-use for further transformations. Determination of the stereochemistry of alcohol (+)-5 The determination of the absolute configuration is crucial for all chiral molecules, but it is especially important for active pharmaceutical ingredients (APIs) like those presented herein, whereas

• help us to plan further steps of the synthesis. Therefore, the stereopreference of the above-studied lipase preparations was evaluated by means of modified Mosher’s methodology described by Riguera et al. [71] In this relatively simple and widely-used experimental approach, the absolute configuration

Trogopterins A–C: Three new neolignans from feces of Trogopterus xanthipes

• Soyoon Baek,
• Xuikui Xia,
• Byung Sun Min,
• Chanil Park and
• Sang Hee Shim

Beilstein J. Org. Chem. 2014, 10, 2955–2962, doi:10.3762/bjoc.10.313

• different in that it did not contain a methoxy group at the C-4′ position nor an ether linkage between C-4 and C-7′ to form a dihydrofuran ring. The absolute configuration of compound 2 was determined by comparing its optical rotation with those of (R)-2,3-diphenyl-1-propanol and (S)-2,3-diphenyl-1-propanol

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• isolated from a Streptomyces griseoflavus (strain W-384) fermentation broth by Zähner et al. in Tübingen, Germany and structurally identified by Zeeck et al. in Göttingen, Germany in 1989–1990 [3][4]. Once the absolute configuration of all the previously unassigned stereogenic centers in the

• . Unfortunately, the diastereomers could not be separated by fractional crystallization as easily as was previously reported for the corresponding 3-(trans-2-nitrocyclopropyl)alanine derivatives [7]. The absolute configuration of the arbitrarily selected nickel(II) complexes (2S,1'R,2'S)-26a, (2S,1'R,2'S)-26b and

• by experimental tests [36]. The initially formed main product (R,R,R)-28 in the aldol reaction of acetaldehyde with 10 had the same configuration at C-2 as the proline unit in 10. The absolute configuration of this nickel(II) complex was determined by a single crystal X-ray structure analysis (see

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• derived from Ginkgo biloba. Its structure was unambiguously established by analysis of HRMS–ESI and spectroscopic data, and the absolute configuration was determined by low-temperature (100 K) single crystal X-ray diffraction with Cu Kα radiation. This compound is structurally characterized by a new

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• ). TDDFT-ECD calculation was proved an efficient method to determine the absolute configuration of separated stereoisomers of bioactive synthetic [19] and natural derivatives [20][21] on the basis of their HPLC-ECD spectra. For the configurational assignment of the separated enantiomers, TDDFT-ECD

• TDDFT-ECD spectra of (2S,15aS)-7d and (2S,15aS)-7b gave good agreement with the experimental HPLC-ECD spectra of the second-eluting enantiomers (Figure 4a,b), which allowed determining the absolute configuration of their second-eluting enantiomers (negative CEs at 370 and 371 nm, respectively) as (2S

De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• ring, the presence of rigidifying planar units and stereocenters collectively govern the shape of a given macrocycle. In fact, we observed that the absolute configuration of C4 of the pyranose ring strongly influenced the shape and reactivity of macrocycle 3 [9]. In 3, the oxygens at C4 and C6 are both

• backbone of the macrocycle whose chirality is dictated by the absolute configuration of the C4 stereogenic center. The topology is a defining feature of this family of [13]-macrodiolides. By virtue of the planar chirality, [13]-macrodiolides such as 3 have an axis of chirality associated with them. We were

• this case the macrocyclic ring. In total it is the balancing of a number of small factors such as rigidification by multi-atom planar units, absolute configuration of stereogenic centers and stereoelectronic effects that dictate the observed structures. Minimum inhibitory concentrations (MICs) against

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• formed from σ-alkyl PdII-complexes F and G by reductive elimination of Pd0 (Scheme 6). Additionally, the X-ray analysis [44] of 53 confirmed the absolute configuration and structure of the six-membered heterocycle (Figure 4). Recently, Wolfe reported a tetrahydrofuran-forming reaction via Pd-catalysed