Efficient synthesis of 3,6,13,16-tetrasubstituted-tetrabenzo[a,d,j,m]coronenes by selective C–H/C–O arylations of anthraquinone derivatives

• Seiya Terai,
• Yuki Sato,
• Takuya Kochi and
• Fumitoshi Kakiuchi

Beilstein J. Org. Chem. 2020, 16, 544–550, doi:10.3762/bjoc.16.51

• examining various carbonyl methylenation methods, we found that the dimethylenation products 6 can be obtained in high yields through methylation of the carbonyl groups, followed by dehydration. Thus, the reaction of 4aa with methyllithium and subsequent treatment of the crude diol with NaH2PO2·H2O and NaI

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• coefficients (Table 2). Nevertheless, the change in selectivity predicted for the benzylated diol analogs of 1α/1β did not match the experimental trend. Similar results were observed with the M06-2X functional (Table 2). The calculations gave a good prediction of the higher OH-3 group’s reactivity, but an

• acceptors and donors. Model Galp 3,4-diol acceptors and data obtained with B3LYP. Synthesis of glycosyl acceptors 1α/β and 2α/β. a) BzCl, pyridine, 0 °C, 2 h; b) BF3·OEt2, MeOH, CH2Cl2, 4 h; c) SnCl4, MeOH, CH2Cl2, 20 h; d) NaOMe/MeOH, CH2Cl2, 0 ºC, 2 h; e) (CH3)2C(OCH3)2, p-TsOH, acetone, rt, 16 h; f) 50

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• diols 1 and 8, thereby indicating that the hemiketals are still fully reducible under standard ketone reduction conditions. Purification of 6 afforded only a 10% overall yield of the diol 8, but the direct conversion of crude intermediate product 6 resulted in a doubling of the overall yield of the diol

• the synthesis of glycomimetic products from sugar lactones, and for the synthesis of various pyrimidines. Proposed retrosynthesis of the free diol 1. Preparation of O-unprotected, trifunctionalized synthons from lactones. Preparation of a variety of β-ketonitriles. Supporting Information Supporting

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• release of TNF-α by BALB/3T3 cells [75]. This cancer prevention activity can be initiated at an IC50 of only 2.5 µM. Other bioactive target molecules structurally accessible from compound 7 could be both epimers of (6R)-2,7,11-cembratriene-4,6-diol either 4S: α-CBT 16 or 4R: β-CBT 17 (Scheme 3). Both were

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• later stage the optical purity could be improved (see below). Diol protection gave dioxolane 14, which underwent Saegusa oxidation to afford enone 15. Subsequent α-iodination gave access to α-iodoenone 16, which could be stereoselectively reduced under Corey–Itsuno conditions to yield allylic alcohol 17

• . The use of a chiral oxazaborolidine catalyst led to kinetic resolution and increased the optical purity of 17 to 95% ee. Deprotection of the diol moiety followed by Stille cross coupling with vinyl stannane 18 finally gave 5 in excellent yield (Scheme 2). Since acremine F (5) can be expected to be the

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• with a Torus DIOL (Waters) or Phenomenex CSP (Lux Amylose-2, i-Amylose-3, i-Cellulose-5), a degasser (DGU-20A5R), a communications module (CBM-20A), and two back pressure regulators BPR A and B (SFC-30A). UV and MS spectra were recorded via photodiode array detection (SPD-M20A) and electrospray

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• byproducts (Scheme 2) [14]. Photooxygenation of 3,4-diphenylbutanal (1) affording the desired diol 6 accompanied by alcohol 9 as the only byproduct was chosen as a model reaction for optimization studies. From a practical point of view it was important that diastereoisomers syn-6 and anti-6 could be

• mixture and oxygen was purged. After the reduction diol 6 was obtained in 12% yield, as a nearly equimolar mixture of syn-(2R,3R)- and syn’-(2S,3S)-6 enantiomers (Table 2, entry 1). So, in the one-pot procedure a decrease in both yield and stereoselectivity was observed as compared to the two-step

• its rather simple structure diol 6 was not previously reported in the literature. The ratio of stereoisomers 6 was determined by HPLC analysis while the absolute configuration of the newly created stereocenter was established using a chiroptical spectroscopic method. Samples of stereoisomers syn-6 and

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• ], helminthosporol (7) [15], bipolenin A (8) [3], secolongifolene diol (9) [15], dihydroprehelminthosporol (10) [1] and sorokinianin (11) [2], and the cytotoxic sesterterpenoid, terpestacin (12) [16][17] (Figure 1). Bipolenin K (1) was isolated as a colourless oil. Its molecular formula was determined as C15H22O3

• ), secolongifolene diol (9), dihydroprehelminthosporol (10) and sorokinianin (11), together with a sesterterpenoid, terpestacin (12). We demonstrated that 6 and 10 have weak necrotic activity against wheat leaves, while 7 inhibited wheat seed germination at 100 ppm. These compounds served as markers for identifying

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• -oxidative Grob fragmentation could make use of a push–pull mechanism between C-17 and C-22, building on acid–base catalysis. Alternatively, an enzyme could cleave the C17–C20 diol oxidatively. Several P450 enzymes have been reported to be capable of cleaving diols, presumably via a ferric peroxo

Synthesis and anion binding properties of phthalimide-containing corona[6]arenes

• Meng-Di Gu,
• Yao Lu and
• Mei-Xiang Wang

Beilstein J. Org. Chem. 2019, 15, 1976–1983, doi:10.3762/bjoc.15.193

• and electron-neutral organic guests [22][23][24][25][26][27][28][29][30][31]. In our previous study we have developed an efficient protocol to synthesize oxygen and sulfur-linked corona[m]arene[n]tetrazines from aromatic diol and dithiol derivatives and 3,6-dichlorotetrazine, respectively, in a simply

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• product in 95% yield, which was converted into tert-butyl (3S,5R)-6-hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate in 14 steps through a β-hydroxy ketone. Keywords: β-hydroxy ketone; cycloaddition; 1,3-diol; isoxazoline; silyl nitronate; Introduction The chiral 1,3-diol structure is widespread in a

• broad spectrum of natural products [1][2]. (3R)-β-Hydroxy-δ-lactone or its open-ring equivalent (3R)-syn-3,5-dihydroxypentanoic acid, is a common structure in naturally occurring mevastatin (or compactin), lovastatin or closely related statins, and synthetic statins. Either the syn or anti-1,3-diol

• chiral β-hydroxy-δ-lactone moiety or its equivalents, pioneered by Wong [42], is equally competitive. Here, we report the preparations of tert-butyl (3S,5R)-6-hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate and related syn-1,3-diol analogs from a chiral 2-isoxazoline (Scheme 1b). This work is part of

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

• diversified compounds. In this review we wish to focus attention on applications of 5–8 in syntheses of biologically important compounds having a 2-amino-1,3-disubstituted propane unit implanted into their structures because vicinal amino alcohol and 2-aminopropane-1,3-diol scaffolds are present in many

• secured in the starting aldehyde introduction of the two others required cis-dihydroxylation of the Z-alkene 111. The highest diastereoselectivity (99:1) was observed at −10 °C providing the aziridine diol (2S,1'S,2'R,1''R)-112 as a major diastereoisomer. The regioselective aziridine ring opening combined

• (Scheme 37) [32]. The major product (2S,1'R)-69b was subjected to Sharpless asymmetric dihydroxylation in the presence of AD-mix-α to give the diol 145a as a major (10:1) diastereoisomer. The ester moiety in 145a was reduced and hydroxy groups were protected to give the tribenzyloxy aziridine (2R,1'S,2'S

Superelectrophilic carbocations: preparation and reactions of a substrate with six ionizable groups

• Sean H. Kennedy,
• Makafui Gasonoo and
• Douglas A. Klumpp

Beilstein J. Org. Chem. 2019, 15, 1515–1520, doi:10.3762/bjoc.15.153

• benzaldehyde. A nickel-catalyzed procedure gives the dipyridyl intermediate 7 [13]. This is easily oxidized to the diketone 8 and reaction of this substance with 2-lithiopyridine gives the precursor 9. The diol 9 is a substrate with six ionizable groups. Upon ionization in superacidic CF3SO3H (triflic acid

• observed from the superacid-promoted reaction of diol 9. This suggests outside deprotonation – and formation of ion 21 – does not occur. The preference for inside deprotonation may be understood to be a consequence of charge–charge repulsive effects. In the case of 21, the five cationic charges are on

• , 123.3, 123.6, 124.2, 128.3, 131.9, 136.4, 138.1, 149.7, 154.4; low-resolution ESIMS m/z: 487 [M + 1], 397, 353, 320, 319, 279, 244; high-resolution CIMS m/z: [M + 1], calcd for C34H23N4, 487.1923; found, 487.1917. Superelectrophilic species. Synthesis of diol substrate 9. Isolated yields of products

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• B could be envisaged with the large pinacol substituent facing the small oxirane ring and thus placing the migrating group antiparallel to the adjacent oxiranyl C–O bond. This may explain the role of the diol substituent on the reaction efficacy (see Table 1). Upon migration and oxirane ring opening

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• incorporating electrophilic groups, we also needed phosphoramidite monomers 26a–c, which contained the sensitive functionalities ester, α-chloroacetamide and thioester, respectively (Figure 2). The synthesis of 26b,c has been reported [40]. Scheme 3 shows the synthesis of 26a. The required 1,2-diol 28 was

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• acid catalysts for over three decades [15][16][17][18][19][20][21][22][23][24][25][26]. Comparatively, interest in the utilization of metal-free organocatalytic oxo-DA reactions began to grow only after Rawal’s group reported a ground-breaking contribution in using a diol molecule, TADDOL, as a

• groups of the TADDOL and the carbonyl oxygen of the aldehyde was proposed to be a crucial factor for the success of this organocatalyst in the reaction. Two years later, they reported another efficient diol-based hydrogen bonding organocatalyst, BAMOL, for catalyzing the same oxo-DA reactions with a

• atropselectivities; (b) different relative spatial arrangement of the CF3- and phenyl-substituents. Torsional angle of biphenyl rings is 104.55(22). Chiral biphenyl diol organocatalysts 1–6. Synthesis of 3. Synthesis of 4. Synthesis of 6. Catalytic asymmetric oxo-DA reactions with stereolabile chiral biphenyl diols

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• (S)-4 with benzyl bromide (BnBr) and Bu4NI in the presence of NaH produced compound 6 (Scheme 2). This was subjected to asymmetric dihydroxylation (ADH) using AD mix-β [K2OsO2(OH)4 and (DHQD)2-PHAL]. The reaction proceeded predominantly from the α-face, resulting in the formation of the 1,3-anti diol

• 7a and 1,3-syn diol 7b in a 91:9 ratio (based on the isolated yields of 7a and 7b, separated by column chromatography). Previously the ADH reaction of a homologue of 6, bearing a methyl substitution and a hydroxy group (instead of benzyloxy group) with AD mix-β also produced the corresponding α

• -alcohol [53]. However, unlike in our case, the reaction proceeded with poor diastereoselectivity irrespective of the dihydroxylating agent used. To confirm the 1,3-anti diol stereochemistry of 7a, it was debenzylated using DDQ/CH2Cl2–H2O to furnish the trihydroxy compound 7a'. The 1H and 13C NMR spectra

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• obtained with artificial metathase ArM 1 using purified Sav samples. RCM activities of catalyst 66 and ArM 3 with substrates 67, 52 and 21. RCM of N,N-diallyltoluenesulfonamide (21) with ArM 4. Selected RCM results of N,N-diallyltoluenesulfonamide (21) and diol 64. ROMP of 7-oxonorbornene derivative 13

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• more concentrated alkaline conditions (5 N KOH) as a result of a pyridinium ring opening–closure process [57]. It was also shown that the ionization of a diol fragment of NAD+ under alkaline conditions plays a very important role in the dissociative cleavage of the glycosyl bond of the “northern

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• . The reduction of ester 76 with LiAlH4 and oxidative cleavage of the resulting 1,2-diol with NaIO4 delivered the highly substituted gem-difluorocyclopropanecarboxaldehyde 77 (72%) possessing a quaternary stereocenter (Scheme 26) [65]. Other examples of post-functionalization involve iodolactonization

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

• )-5 which after O-benzylation provided an inseparable 1:3 mixture of compounds 8a and 8b. A six-carbon chain was shortened by a diol formation–diol cleavage sequence followed by aldehyde oxidation and esterification to give 9a and 9b after chromatographic separation. They were transformed into (2S,3R

• give acid 16. To complete the synthesis of di-tert-butyl ester of (2R,3S)-2 compound 16 was first transformed into the ester and later deprotected to the diol 17 which was selectively oxidized, again esterified and finally the phenylsulfonyl group was removed electrochemically (Scheme 4) [52]. The

• derived from D- or L-tartaric acids can be used as starting materials in syntheses of enantiomers of 3,4-dihydroxyglutamic acids since they contain a vicinal diol fragment of the known stereochemistry. To demonstrate this strategy cyclic imides 106a (R = TBDMS) and 106b (R = Ac) readily prepared from L

First synthesis of cryptands with sucrose scaffold

• Patrycja Sokołowska,
• Michał Kowalski and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2019, 15, 210–217, doi:10.3762/bjoc.15.20

• sucrose scaffold (e.g., 4) can be also prepared successfully [15][16]. All macrocyclic derivatives, shown in Figure 1, were prepared from hexa-O-benzylsucrose 3 by a connection of the terminal positions of glucose (C6) and fructose (C6’) units. Results and Discussion Diol 3 may be also used as a starting

• Figure 2) is, however, problematic, because of steric hindrance. The approach shown on route b (Figure 2), in which the terminal positions are elongated to avoid these difficulties, seems to be more feasible. Diol 3 was, thus, extended at both terminal positions by five atoms by reaction with bis(2

• connected to the nitrogen atoms (-CH2N units), and thus this observation confirms the presence of the crown-unit 8 in the structure. Although the first approach to sucrose cryptands was very successful, the strategy based on sucrose diol 3 has several limitations. First of all, the cavity in cryptand 11 is

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• selective formation of the β(1→4) linkage in the [2 + 2] coupling. Cleavage of the anomeric 4-methoxyphenyl group followed by treatment with trichloroacetonitrile and DBU gave glycosyl donor 1 in high yield. For the synthesis of acceptor 2, diol 6 was selectively acylated at position 6 using 1.1 equiv of

Systematic synthetic study of four diastereomerically distinct limonene-1,2-diols and their corresponding cyclic carbonates

• Hiroshi Morikawa,
• Jun-ichi Yamaguchi,
• Shun-ichi Sugimura,
• Masato Minamoto,
• Yuuta Gorou,
• Hisatoyo Morinaga and
• Suguru Motokucho

Beilstein J. Org. Chem. 2019, 15, 130–136, doi:10.3762/bjoc.15.13

• )-limonene-derived diol and its corresponding five-membered cyclic carbonate were prepared. The diol (cyclic carbonate) comprises four diastereomers based on the stereochemical configuration of the diol (and cyclic carbonate) moiety. By choosing the appropriate starting compounds (trans- and cis-limonene

• their characteristic signals. Keywords: cyclic carbonate; diastereomer; diol; limonene; NMR; Introduction (R)-Limonene (LM) is a naturally occurring terpene, and therefore a very attractive and renewable resource [1]. Its derivatives have versatilely and widely been studied [1][2][3][4]. Otherwise

• corresponding LMdiol 2d [27]. Notably, the structure of 2d was confirmed by X-ray analysis. It has been reported that reduction of the 5CC moiety with LAH gives the corresponding diol with the same stereochemical configuration at the carbon atoms as of the original 5CC moiety [28][29]. Such a reduction with LAH

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• inseparable mixture of two diiodo-substituted products was unveiled. The major product was the bicyclic gem-diol 4 and the minor one the corresponding ketone 3. We hypothesize that the α,α-difluoroketone 3 was formed through a cyclopropane ring-opening followed by the addition of the electrophilic iodine in

• accordance to what was reported by the Dilman group [40]. The α,α-difluoroketone 3 rapidly underwent hydration in a reversible way to form the gem-diol 4. The stereochemistry of compound 4 could be assessed indicating the selective formation of the β-nucleoside with the addition of the iodine at the 7