Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• an azide nucleophile. The synthesis of allyl alcohol C from D-glucose was reported by us earlier. Our synthesis started with the homoallyl alcohol 3 (with defined ‘R’ absolute configuration at the C3-quaternary center) that is obtained from D-glucose as reported earlier by us in 37% overall yield [15

• the ratio of 18:82 in 83% yield. With the understanding of SAE mnemonic, we assigned the absolute configuration in epoxide 8 as 7S,8S and in epoxide 9 as 7R,8R. Subsequently, major isomers of epoxy alcohols 8 and 9 were individually subjected to regioselective epoxide ring opening using trimethyl

• orientation indicating 5’S absolute configuration as anticipated from the SAE mnemonic in compound 8. As the C5’ and C6’ stereocenters in 14 are derived from the regioselective SN2 opening of epoxide 8 by NaN3, the configuration at the C6’ (carrying azido group) was therefore assigned as 6’R. In the 1H NMR

Enantioselective addition of diphenyl phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified organocatalysts

• Hee Seung Jang,
• Yubin Kim and
• Dae Young Kim

Beilstein J. Org. Chem. 2016, 12, 1551–1556, doi:10.3762/bjoc.12.149

• yield and enantioselectivity (Table 2, entry 13). The absolute configuration of adducts 3 was determined to be R by comparison of the specific rotations and HPLC properties with literature values [36.37]. The stereochemical outcome in the above addition reaction was rationalized by a proposed

Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene

• Frederick J. Seidl and
• Noah Z. Burns

Beilstein J. Org. Chem. 2016, 12, 1361–1365, doi:10.3762/bjoc.12.129

• isomer 6 in 46% yield and 84% ee (Table 1, entry 1). Constitutional isomer 7 was also observed (4:1 ratio of 6:7), as well as dibromide 8 and other racemic brominated byproducts (see Supporting Information File 1). The absolute configuration of 6 was assigned through its subsequent conversion into

• (−)-anverene (1, see below), the absolute configuration of which was determined by the isolation chemists on natural material by X-ray crystallography [10]. Interestingly, using the same enantiomer of ligand, the bromochlorides derived from prenol and homoprenol (5) have the same absolute configuration. This

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• not shown). The absolute configuration of cyclopentanes 3’ and 3’’ were determined based on the derivatives 7h’ and 7h’’ of 3h (Scheme 2) [95]. We proposed two possible transition states (TS) 8a’ and 8a” to rationalize the observed configurations (Scheme 3). The trans-C=C double bond in iminium ion 4

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• nucleophiles for the conjugate addition–enantioselective protonation of α-aminoacrylates (vide infra). In 2010, Mikami and co-workers reported a hydrogen atom transfer strategy for the synthesis of β-perfluorobutyl-α-amino ester 13 in low yield and modest enantioselectivity, and the absolute configuration of

• , Frost reported that using the same catalyst system, phenyltrimethoxysilane (49a) could be added to dimethyl itaconate (50) with modest enantioselectivity and without defining the absolute configuration of the major stereoisomer (Scheme 11b) [32]. Darses and Genet reported the highly enantioselective Rh

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• , sulfinate ester 11 was synthesized and subjected to alkylation with (5-trimethylsilyl)-4-pentynylmagnesium iodide. Because the order of addition was reversed, it is important to note that 12 has the opposite absolute configuration. In this way, sulfoxides containing m-xylyl, o-methoxyphenyl, and cyclohexyl

• unsatisfactory (Table 3, entry 5). m-Xylyl 19 was similarly disappointing (Table 3, entry 6). However, o-anisyl 20 was interesting in that it was able to maintain high enantiomeric ratios of 14 in both THF and acetone and with the same absolute configuration (Table 3, entry 7). This could possibly be due to a

• lithium aluminum hydride in excellent yield. The absolute configuration of the [3.1.0] pyrrolidines was assigned by analogy to 76, which was determined to be (R,R) by single crystal X-ray crystallography. Mechanistic studies After having successfully developed this synthetic methodology, a few questions

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• , this approach enables a more versatile elaboration of different configurations as present in the manzacidins and/or originally postulated for this class of marine natural products. Notably, the absolute configuration of manzacidin C was initially proposed as shown in Figure 1 [2] and subsequently

• dimer in the crystal lattice, which is stabilized by two hydrogen bonds between the urea oxygen atoms and the tosyl-protected nitrogens. This also unambiguously confirms the absolute configuration of 39 and corroborates our prediction of the asymmetric adduct 31. We then attempted the installation of

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• )-selectivity (up to >20/1 Z/E ratio, Scheme 52) [70]. Besides, the absolute configuration of the products can be controlled by the chiral CPA, selectively affording the (R)- or (S)-enantiomer based on the catalyst used. 3-Indolylmethanols have been recongnized as reactive precursors in organic synthesis for

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• correlations for the cis- and trans-configuration. However, the absolute configuration of the chiral centers could not be resolved yet. Moreover, the origin of the different isomers is not clear. Due to their alleged instability upon exposure to air and light, one could speculate that isomerization occurs

• . Structure elucidation was achieved via extensive NMR measurements. The absolute configuration of the chiral centers could be resolved through comparison of the experimental CD spectrum with calculated data. This metabolite showed inhibitory activity towards the bacterium Arthrobacter crystallopoietes with

• miuraenamide A (31) the absolute configuration was determined. Marfey´s method was employed to show that L-alanine and N-methyl-D-tyrosine are present. Furthermore, after acid hydrolysis, methylation and application of modified Mosher´s method the absolute configuration at the oxygen bearing C-9 was deduced as

Asymmetric α-amination of 3-substituted oxindoles using chiral bifunctional phosphine catalysts

• Qiao-Wen Jin,
• Zhuo Chai,
• You-Ming Huang,
• Gang Zou and
• Gang Zhao

Beilstein J. Org. Chem. 2016, 12, 725–731, doi:10.3762/bjoc.12.72

• a single recrystallization step (Scheme 2). The product could be deprotected to provide the known compound 5 with no deterioration in enantioselectivity. The absolute configuration of 3a was deduced to be S by comparison the specific optical rotation data of 5 with literature data [10][12], and the

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• . Similarly, H-13 unveiled the same interactions with H-1 and H-9 while H-14 correlated with H-8 (Figure 4). In order to determine the absolute configuration of the compounds 1–3, ECD spectra prediction was used [36][37]. The absolute configuration of 1 was assigned as 2R, 6S, 7R, 10R, and 11S by ECD analysis

• similar interactions with H-1 (δ 1.72) and H-9 (δ 1.56, 1.67). The absolute configuration of 2 was determined to be 2R, 3S, 6S, 7R, and 10S by ECD analysis. As compound 1, two Cotton Effects (CE) from the n→π* transition of the α,β-unsaturated lactone were revealed at 225 and 275 nm with alternative signs

• aglycone [39]. The absolute configuration of 3 was assigned as 1R, 6R, 7S, and 10S. Three CE's were observed on the experimental ECD spectrum at 240, 305 and 350 nm due to the n→π* transition of the α,β-unsaturated ketone. The foregoing data led to identify 3 as 6-hydroxyguaiane congener (Figure 2) and the

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