Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• ] and L2 [3] are based on the o-nitrobenzyl scaffold [23][24] and expose a hydroxy group that serves as glycosyl acceptor in the first AGA cycle (Figure 1B). While L1 displays a flexible aliphatic chain terminating with a primary alcohol, L2 carries a secondary benzylic alcohol. Upon irradiation with UV

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• -derived ketimines 49 was reported by Vila, Pedro and co-workers. Regioisomeric hydroxyquinolines were tested in this reaction to facilitate the electrophilic aromatic substitution on the ortho-carbon atom with respect to the hydroxy group in quinolines 15. The reaction affords oxindole scaffolds 116 with

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• position. An HMBC correlation from H-4 to the carbon atom at 32.7 ppm (C-7) allowed the linkage of the phenol moiety with an n-pentyl sidechain in meta position to the hydroxy group. The spin system of the latter includes proton resonances at δH 2.54 (H-7a), 2.62 (H-7b), 1.49 (H-8), 1.25 (H-9), 1.25 (H-10

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• the enol form, a C-attack (path a) furnishes cyclopropane 1, and an O-attack (path b) furnishes dihydrofuran 8. When the R1 group becomes bulkier, the hydroxy group may be far from the reaction site because of the steric repulsion in the stable conformation. Another possibility is that the bulky

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, 789–799, doi:10.3762/bjoc.19.59

• indicated that the compound possesses the same two pentasubstituted benzene rings, suggesting an axially symmetric structure. The methoxy group is situated at C-3, as determined by the HMBC correlation (Figure 2 and Figure S12 in Supporting Information File 1) of H3-11/C-3 (δC 154.1). The hydroxy group and

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

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

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• a 6π-electrocyclization of the hexatriene system and ESIPT-induced contraction of the pyranone ring. At the same time, the blocking of the ESIPT-promoted process via alkylation of the hydroxy group allows one to realize the regiospecific cyclization of the triene system. Based on these previous

• 11g–j were confirmed by 1H, 13C NMR spectroscopy and high-resolution mass spectrometry. In the 1H NMR spectra of the products, characteristic singlets corresponding to the protons of the dihydropyranone fragment in the region δ 5.3–5.4 ppm and the protons of the hydroxy group in the region δ 5.4–5.5

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

• -17 and C-14 as well as the appearance of the H3-17 as a singlet signal confirmed the connection of a hydroxy group at C-14. The relative configuration of 1 was characterized by NOESY spectra. In the NOESY experiment (Figure 3), the cross-peak between H-8 and H3-20 suggested these protons to be syn

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• (Scheme 47B). The authors concluded that the new structure 186 is formed by intramolecular ring opening of the oxazolidine unit initiated by the hydroxy group either following the aldol condensation or during the reaction workup. In 2021, Zhang and Oestreich presented a Cu-catalyzed tandem conjugate

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• salicylaldehydes with EWGs failed to react. The authors hypothesized the reaction mechanism begins with the association of the Rh(III) catalyst with the hydroxy group of salicylaldehyde (151a) resulting in a selective cleavage of the aldehyde C–H bond producing the rhodocycle 153 which side-on coordinates with the

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• as potential inhibitors of cathepsins. The phosphorus atom by default should mimic the tetrahedral intermediate, but this role may also be played by the hydroxy group present in hydroxyphosphonates, which mimic the carbonyl carbon in the peptide bond by forming a hydrogen bond with the amino group of

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• ions. Further demethylation [40] and oxidation of the thioether followed by thermal elimination of the intermediate sulfoxide gave 2 in 98% yield after two steps (Scheme 7). The authors also achieved the synthesis of (±)-1 from combretastatin D-2 (2). Protection of the hydroxy group in compound 2 using

• alcohol 64. The formation of the double bond from alcohol 64 proved to be problematic, thus, replacement of the hydroxy group by iodine [47] followed by dehydrohalogenation using an excess of KF afforded methyl combretastatin D-2 (28) in 87% yield after two steps (Scheme 11). The authors also described a

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• complexation can lead to a significant solubility enhancement of poorly water-soluble molecules, and therefore it can enable the biological testing of drugs, which would otherwise not be possible by any other means [2][3]. Monosubstituted CDs contain only one hydroxy group modified with a functional group. In

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• -arylalkylated iminosugars 26–28, the naphthyl derivative 28 showed the strongest activity against AMAN-2 (Ki = 18 μM) and a selectivity similar to the p-iodobenzyl analog 27. These findings suggest that both the C-5 hydroxy group and R-configuration at the corresponding carbon are necessary for retaining the

• hydroxy group of the (R)-1-hydroxyethyl moiety of 29. The interaction with Trp95 is also significant but to a lesser extent (−5.8 kcal mol−1), and the overall interaction of 29 with the Phe206-Trp415 hydrophobic pocket is insignificant (less than −1.2 kcal mol−1). Therefore, the main contributors remain

• derivatives were synthesized for α-mannosidase inhibition studies. Their evaluation revealed that deoxygenation at C-5 (derivatives 7–10) provided the least effective inhibitors of the target Golgi enzymes. The comparison between iminosugars 17–20 and their C-5 epimers 26–29 showed that the hydroxy group must

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• single hydroxy group on the central eight-membered ring and 3(11)-epoxyhypoestenone (55) shows a surprising oxa-bridge between the A and C rings, an α,β-unsaturated ketone on ring C, and an endo-alkene into the cyclooctene ring. Recently, Chen et al. reported the synthesis of the tricyclic core structure

• Aplysia dactylomela and red seaweed Laurencia poitei, bears a rare rearranged trans-bicyclo[6.3.0]undecane isoprenoid skeleton. Its structure is – only – composed of a bicyclic ring with fused five- and eight-membered rings, with a hydroxy group at the junction cycle [37][38]. In 1996, Fürstner and

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

• functionality (hydroxy group) and an enone system within the same molecule are needed to accelerate the intermolecular RC reaction. Results and Discussion A retrosynthetic plan for the synthesis of (±)-incarvilleatone (1) and (±)-incarviditone (2) is delineated in Scheme 2. We envisaged that both the natural

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• suitable starting material for the SmI2-promoted pinacol coupling, directed by the free hydroxy group, affording a complete selectivity in the formation of the 7-membered ring B. The synthesis of grayanotoxin III was then achieved by acetylation of the secondary alcohols, oxidative cleavage of the MOM

• synthesis started from 3-hydroxy-2-methoxybenzaldehyde (34), which was converted into Grignard reagent 35 and added onto 3-methylbut-2-enal (Scheme 6). A sequence involving Claisen rearrangement, Roskamp homologation, diazo transfer and intramolecular cyclopropanation led to intermediate 37. The hydroxy

• group on C6 was introduced after cyclopropane ring-opening, ketone protection, epoxidation and reductive ring-opening of the resulting epoxide. A one-pot β-keto phosphonate formation/Horner–Wadsworth–Emmons reaction with formaldehyde afforded 38, a precursor for the key oxidative dearomatization-induced

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• ) would again have a reactive phenolic hydroxy group which could potentially be involved in post-condensational transformations such as intramolecular oxa-Michael addition (Scheme 1). Herein, we report our findings obtained in the course of investigating the viability of this strategy. Results and

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