Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• antimicrobial activity. Moreover, antiviral activity was also confirmed for aggregatin B [52] containing a 7-membered lactone ring, in which the β-position hydroxy group was dehydrated (Figure 1). Monocrotaline is a kind of pyrrolizidine alkaloid and was isolated from seeds of Crotalaria spectabilis in 1935 [53

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• differed from the above path by leaving the hydroxy group of all intermediate 4-hydroxypyridine derivatives 12–15 unprotected [19]. Moreover, instead of azo coupling or nitroso formation, a simple nitration protocol with nitric acid to give the nitro derivative 13 and subsequent reduction with Raney nickel

• by the introduction of a hydroxy group at C6 under Sandmeyer conditions to give 29 (Scheme 5). To remove the benzyl group, Pearlman’s catalyst in the presence of hydrogen was applied to provide 1-deazahypoxanthine (30) in seven steps and 24% overall yield. Our new route to 1-deazahypoxanthine (30

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• for obtaining 1. The desired highly halogenated aryl alkenyl ether 2a was obtained, but the yield was unacceptably low (Table 1, entry 1). The low conversion is attributed to use of an insufficient amount of KOH, which was used as a base for deprotonation of the phenolic hydroxy group and acidic C–H

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• SnCl2-catalyzed coupling reaction [20] between 21 and 22 afforded β-keto ester 23, which was then reduced to the corresponding β-hydroxy ester 24 by K-Selectride (dr > 20:1), and subsequent acidic removal of the acetonide furnished diol 25. The stereochemistry of the newly generated hydroxy group was

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• hydroxy group were positioned at C-3 and C-4 of the aromatic ring, respectively, based on NMR chemical shift data comparison with related marine natural products [19]. The E configuration for the oxime in 1 was assigned by the diagnostic carbon chemical shifts of the benzylic methylene (C-7, δC 27.8) [21

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• cyclooctene endoperoxide, prepared by photooxygenation of cis,cis-1,3-cyclooctadiene, with zinc gave a cyclooctenediol and then benzylation of the hydroxy group yielded dibenzylated cyclooctene. Oxidation of the latter compound by OsO4/NMO followed by mesylation of the hydroxy group provided bis(benzyloxy

• the diazide 9 could not form. The configuration of the hydroxy group in 11 was determined by the cross peak between the proton H-2 and the protons H-1 and H-3 in the COSY spectrum. Moreover, the fact that the proton H-1 gives a positive NOE clearly indicates that it should have a cis configuration

Sinensiols H–J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring

• Qinfeng Zhu,
• Beibei Gao,
• Qian Chen,
• Tiantian Luo,
• Guobo Xu and
• Shanggao Liao

Beilstein J. Org. Chem. 2022, 18, 1410–1415, doi:10.3762/bjoc.18.146

• yellow amorphous powder. The negative HRESIMS [M − H]− at m/z 371.1133 (calcd for 371.1136) suggested its molecular formula to be C20H20O7, corresponding to 11 degrees of unsaturation. The IR spectrum showed absorption bands characteristic of hydroxy group (3450 cm−1), carbonyl (1765 cm−1), and aromatic

• quite similar to that of (E)-5,5′-(but-2-ene-1,4-diyl)bis(3-methoxybenzene-1,2-diol) [15]. The main difference was that the hydroxy group at C-4 and C-4′ in (E)-5,5′-(but-2-ene-1,4-diyl)bis(3-methoxybenzene-1,2-diol) was substituted by a methoxy group in 2, which was confirmed by the HMBC correlation

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• studies for the conversion of enol phosphate to the corresponding ketone were accomplished using an unprotected primary alcohol. However, it appeared that hydroxy group protection was necessary: control experiments made on the racemic cycloadduct 8 showed that basic hydrolysis of the enol phosphate led to

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• of the hydroxy group to the terminal double bond of the allene in compound 3. Another key step is the Ti(III)-mediated straightforward synthesis of this α-hydroxyallene, which could be achieved through a regioselective Barbier-type coupling of a propargylic halide (1-bromo-2-butyne) with the aldehyde

• alcohol 6 with amberlyst-15® leading to the monoterpene 1. Other systems tested for the elimination of the hydroxy group in 6 were pyridinium p-toluenesulfonate (PPTS) and camphorsulfonic acid (CSA), that gave poorer results, failing to afford a single product. On the other hand, lactone 5 could also be

Synthesis of protected precursors of chitin oligosaccharides by electrochemical polyglycosylation of thioglycosides

• Md Azadur Rahman,
• Kana Kuroda,
• Hirofumi Endo,
• Norihiko Sasaki,
• Tomoaki Hamada,
• Hiraku Sakai and
• Toshiki Nokami

Beilstein J. Org. Chem. 2022, 18, 1133–1139, doi:10.3762/bjoc.18.117

• blocks can reduce the number of steps in the total synthesis. However, it requires manipulation of the anomeric leaving groups and deprotection of the protected hydroxy group at the 4-position prior to glycosylation. Although automated electrochemical assembly, which is a one-pot iterative synthesis of

• as the optimal amount of electricity to prevent formation of byproducts, such as hydroxy-substituted sugars that carry an anomeric hydroxy group instead of the ArS group. Although we tested other ammonium triflates, such as tetraethylammonium triflate and 1-butyl-1-methylpyrrolidinium triflate as

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• -NOESY correlation with H-6 (δH 6.98, s). The HMBC correlations of H-6 to C-8 (δC 136.3), C-10 (δC 118.9), C-7 (δC 151.7), C-5 (δC 123.6), and C-8’’ (δC 119.1) suggested that C-5 is the coupling site on this unit, and C-8 was substituted by a hydroxy group. Finally, the structure of 1 was determined as a

• addition, radical cation addition, and electrophilic aromatic addition, have also been proposed [1][10][29]. A proposed mechanism is depicted in Scheme 2: First, the hydroxy group on the A- or B-ring is converted into a radical by a P450-induced single-electron transformation. The resulting radical then

• equal to the monomers 4 and 6, 1 displayed a roughly twofold radical scavenging capacity (Figure S9, Supporting Information File 1). This is in agreement with the previous report that the configuration of the hydroxy group of the B-ring plays a key role in the antioxidant activity [34]. Thus, CYP158C1

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• ) affording high yields of the corresponding monobrominated products. The reaction of halogen-substituted phenols also showed higher yields with no exchange of halogen atoms during the course of the reaction (products 2g–j, Scheme 3). As expected, exclusive ortho-bromination to the phenolic hydroxy group was

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• reaction of phenacyl bromide, malononitrile, dialkyl but-2-ynedioate, and triphenylphosphine has been already reported, in which diethyl 3-phenyl-5,5-dicyanocyclopent-2-ene-1,2-dicarboxylates were produced by further elimination of a hydroxy group [30]. In the present reaction, the hydroxy group is still

• displayed a singlet at 3.52 ppm for the hydroxy group and two singlets at 3.24, 3.96 ppm with J = 14.8 Hz for the two diastereotopic protons of the cyclic methylene unit. The single crystal structure of compound 3k was successfully determined by X-ray diffraction analysis (Figure 1). From Figure 1, it can

• be seen that the C–C double bond is connected to two methoxycarbonyl groups. Though one hydroxy group exists on the reactive allyl position and benzyl position, it still is present in the molecule and did not give the cyclopentadiene by further elimination of water. In order to obtain the

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• gave the corresponding (2-substituted pyrimidin-4-yloxy)acetates 6–9. In order to replace the 2-methylsulfonyl group with a hydroxy group, we tested several techniques. It was found that heating compound 5 with water in dimethyl sulfoxide at 100 °C or boiling for 1 h in water led to hydrolysis of both

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• product. The functional analysis of FtmOx1 indicated that the enzyme accepts fumitremorgin B as a substrate and catalyzes the formation of verruculogen and a C13-oxo product, through the installation of an endoperoxide bridge between C21 and C27 of fumitremorgin B and oxidation of the C13-hydroxy group of

• endoperoxide with a C26 radical intermediate. Finally, the radical is quenched by hydrogen atom donation from Tyr224, to form verruculogen and a tyrosyl radical for the next round of the reaction. The tyrosyl radical at Tyr224 is also involved in the oxidation of the C13-hydroxy group of verruculogen to a C13

• located on the protein surface and solvent-exposed, the distance between C21 of fumitremorgin B and the iron center is 4.6 Å and the hydroxy group of Tyr68 is near C26 of fumitremorgin B (Figure 3C). Moreover, Tyr68 is located close to C13 of fumitremorgin B, at a distance of 3.7 Å. The comparison between

A study of the photochemical behavior of terarylenes containing allomaltol and pyrazole fragments

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2022, 18, 588–596, doi:10.3762/bjoc.18.61

• complex mixture of products. At the same time the blocking of ESIPT-processes by the modification of the hydroxy group allows one to direct the photoreaction exclusively to the pathway of 6π-electrocyclization of the 1,3,5-hexatriene system. Thus, the study of the photochemical properties of similar

• we can assume that the key difference of the related pyrazole derivatives considered in this report is the absence of a pathway associated with 6π-electrocyclization. Therefore, we supposed that for the corresponding pyrazoles 12 containing a hydroxy group in the allomaltol fragment only ESIPT

• considered photoprocess. Probably, the DMF molecule forms an intermolecular hydrogen bond with the hydroxy group of the allomaltol fragment leading to complete suppression of the ESIPT process. Finally, AcOH was used as a solvent for the photochemical synthesis of α-hydroxy-1,2-diketone 14a. The starting

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• bromopropargylic alcohols under the reported conditions. The bromopropargylic alcohols are readily available from acetylenic alcohols and hypobromite [22] or N-bromosuccinimide [23]. The presence of the hydroxy group expands the synthetic potential of these bromoacetylenes. Thus, we have recently demonstrated a

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• oxygen atom. A comparison of the NMR data with 3 revealed that the chemical shifts of CH2-24 are significantly shifted upfield. In contrast, all other resonances are highly conserved and no difference in the splitting pattern was observed. This suggests the presence of an electron-donating hydroxy group

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• hydrophobicity is important to inhibition of neuraminidase as the most potent compounds possess hydrophobic aromatic substituents. Conversely, increase in polarity results in weak inhibition (ca. 5%) as noted for compounds bearing substituents with nitrogen or a hydroxy group (3d–g). In fact, the higher polarity

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• absorption bands at 325 and 293 nm indicated the presence of a coumarin-type chromophore. The IR spectrum of 1 demonstrated absorption bands characteristic for an hydroxy group (3266 cm−1), α,β-unsaturated carbonyl group (1739 and 1701 cm−1), and an aromatic ring (1624 and 1457 cm−1). The 1H NMR spectrum of

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• only solvent-ionizing power. Shallow maxima observed when selectivity values (S, indicating the extent of product formation involving replacement of the chloride by the alkoxy group from an alcohol molecule reactive to replacement by the hydroxy group of a water molecule) could be due to two reaction

• or water molecule, leading to four possible reaction pathways, with two leading to replacement of the chloride by an alkoxy group and two to replacement by a hydroxy group. In a 2007 article [49] with “Dual Reaction Channels” in both the title and the “Key Words,” there is extensive dispersal between

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• -methyltetrahydrofuran following a chemoenzymatic pathway. Whereas, the protection of the primary hydroxy over the lone secondary hydroxy group in the key azido sugar precursor was achieved using bulky tert-butyldiphenylsilyl chloride (TBDPS-Cl) in pyridine in 92% yield following a chemical synthetic pathway. The

• % overall yield starting from compound 11, respectively (Scheme 2). The use of lipase as biocatalyst was employed for the selective acetylation of the primary hydroxy group present in trihydroxy nucleosides 14a,b. This led to the screening of two different lipases, viz Candida antarctica lipase-B (CAL-B

• temperatures ranging from 25–45 °C in an incubator shaker at 200 rpm. Lipozyme® TL IM (10 wt % of the substrate) in 2-Me-THF at 40 °C was found to be the most suitable solvent for exclusive acetylation of the primary hydroxy group present in compounds 14a,b in quantitative yields (Scheme 3). Further, the

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• supported the structures of the Schiff bases 3. Additionally, the hydrogens of the hydroxy group were observed at 13.12 ppm, on average. The analysis of the 13C NMR spectra in CDCl3 for the new Schiff bases 3 showed chemical shifts in the 162.68–164.71 ppm range for the CH=N moiety, which agrees with

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• isoxazolidine-4,5-diols in the presence of anhydrous cerium chloride [17], which proceeded in a highly syn-diastereoselective manner due to the presence of the unprotected hydroxy group in the α-position. Accordingly, the diol 3 will be examined in the reaction with vinylmagnesium bromide with an emphasis on

• the expected high syn diol diastereoselectivity (Scheme 1). The obtained anti,syn-(hydroxyamino)alkenol 4 will be then subjected to reductive cleavage of the N–O bond. Next, a key intermediate epoxide 5 with the desired syn (threo) configuration between the hydroxy group and the epoxide oxygen could

• be prepared by substrate-directed epoxidation. A subsequent SN2 intramolecular epoxide ring-opening cyclization could provide an N-Cbz-protected pyrrolidine derivative with a hydroxymethyl group at C-5 and with trans configuration relative to the hydroxy group at C-4. Finally, (±)-codonopsinol B (1

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• incorporated into the growing DNA strand. However, the absence of a 3'-hydroxy group prevents further strand elongation. The anticancer and antiviral activity of 2’,3’-dideoxynucleosides is mainly based on inhibition of DNA synthesis, either through the chain termination process or by competitive inhibition [3

• with natural nucleotides for incorporation into the growing HIV DNA chain. The result if the triphosphate is taken up is the termination of the chain elongation because the drug lacks the 3’-hydroxy group on the deoxyribose ring that is necessary for the sugar–phosphate linking as shown in Figure 2

• % aqueous sulfuric acid, the isopropylidene group of 13 was selectively deprotected at 70 °C in dioxane to obtain diol 14. This diol was further cleaved using lead tetraacetate, and further reduction with sodium borohydride produced compound 15. The 5'-hydroxy group of 15 was then treated with tert