Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• ) and displayed two strong HMBC correlations to C2 and C5, which connected these carbons through a nitrogen atom to establish a pyrrole ring, and also a hydroxy group at the alkyl terminus. Another methyl proton at δH 3.85 was of a methoxy group (δC 51.4) and had only one HMBC correlation to C6, which

• oxymethine H15, which in turn was correlated with a methylene H214. The pyrrole moiety with the same substituents as 1 was deduced from HMBC correlations. Therefore, compound 2 was determined to have a non-branched alkyl chain with a hydroxy group at C15. Meanwhile, 3 possessed a terminal ethyl group, which

• was connected to an oxymethine H14 in a COSY spectrum, thereby establishing a non-branched alkyl chain with a hydroxy group at C14. The specific rotation values of 2 and 3 were calculated to predict their absolute configurations. For the flexible molecules 2 and 3, thousands of conformers may exist

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• bifunctional sulfide (S)-1a (10 mol %) bearing a hydroxy group. This reaction yielded the desired δ-valerolactone product 3a with good yield and enantioselectivity [83% yield, 86:14 enantiomeric ratio (er)]. We further tested the reaction of 2a with a hydroxy-protected sulfide catalyst (S)-4 under the same

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• chlorine atom in the chlorovinyl fragment to the hydroxy group, probably under the influence of water (Figure 4). It is worth noting that the synthesis of Ugi bisamides 5–8 (Table 1) yielded compounds 10 and ketobisamide 12 in some cases. For example, in the Ugi reaction involving benzyl isocyanide (4b

• hydroxy group and the formation of a different type of peptidomimetic, namely ethyl 4-(3-(N-(4-R2-phenyl)-2-chloroacetamido)-4-(R1-amino))-4-oxobutanoyl)-3,5-dimethyl-1H-pyrrole-2-carboxylates. It was also found that these two unusual products of acidic transformation were observed as byproducts of the

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• explained by the intramolecular hydrogen bond formed between the hydroxy group and the carbamide substituent, which explains the high deshielding observed in the 1H NMR spectra for the signal of the OH group (around 8.5 ppm). As before, we also explored the stereochemical outcome in the synthesis of

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• . The specific quinones formed were guided by the position of an initial hydroxy group on the polycyclic aromatic hydrocarbon. An available para-position in the PAPs gave p-quinones, while hydroxy groups in the 2- or 3-position led to o-quinones. The substrates were analysed by cyclic voltammetry for

• radical (potassium nitrosodisulfonate) [13] or catalytic systems like methyltrioxorhenium(VII) (MeReO3) [14] and 2-iodobenzenesulfonic acids (IBS)/Oxone® [15] led to either p-quinones or o-quinones, depending on the substituents in the para-position to the hydroxy group. Recently, hypervalent iodine

• of the cell. It was building up in consecutive experiments but was reduced again by cleaning of the electrodes. The experiments collected in Table 3 and Table 4 typically had residence times between 3 and 7 minutes. Substrates with the hydroxy group in the 2- or 3-position, i.e., 1a, 3a, 3c, and 6a

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• mesylate 1, whose basic treatment promoted the substitution of the mesylate group at C-21 by the 17α-hydroxy group and the oxetane ring formation in a 16% yield (Scheme 1) [10]. Winkler et al. developed the synthesis of alkylated derivatives of 17-spirooxetanosteroids from non-alkylated frameworks (Scheme

• sodium hydride, yielding moderate yields (ranging from 23% to 68%). The cyclization initially formed the non-isolated intermediate i, which was oxidized by molecular oxygen from air, introducing the hydroxy group at the α-position of the cyano group. The protocol utilised mild conditions and short

• -2H-furan-3-one framework at position C-17 [22]. The one-pot procedure involved the condensation of diethyl oxalate with the α-hydroxy ketone moiety of derivatives 28, immediately followed by a cyclization between the 17α-hydroxy group and the carbonyl group of the α-ketoester in 29. Spiro compounds

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• hydroxy group of the aglycon. Cotylenin exhibits promising anticancer activity, and its diterpene aglycon, cotylenol (1), was isolated from the filamentous fungi such as Phomopsis amygdali and Cladosporium sp. 501-7W (Scheme 2A) [20][21][22]. Brassicicenes, differing in oxidation levels from 1, have been

• recombinant SorbC enantioselectively introduced a hydroxy group to generate the reactive intermediate (S)-34 [34]. Cyclohexadienone (S)-34 was relatively stable in aqueous reaction solvents, however, quenching the enzymatic reaction by the addition of organic solvents led to homo-dimerization. Based on these

• substrate tolerance of MaDA for chemical probe design. After several attempts, Lei and co-workers designed and synthesized chemical probe 49 bearing a diazirine photoaffinity labelling unit with an alkyne tag on the phenolic hydroxy group of biosynthetic intermediate 44 (Scheme 5B). The treatment of

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• in Figure 3a. This indicates a ligand exchange of the hydroxy group resulting in a loss of electron density and the formation of the alkoxy-NHI 2'. The chemical shift is consistent with previously measured alkoxyiodanes [32]. The experiments were repeated using activated p-tolylmethanol (3a), again

• exchanged with the hydroxy group of the NHI [21]. No such ion was measured in the mixture before heating. This ion therefore indicates an I–Cl bond in the activated iodane. Starting from I-OH, in a potential path a) formation of hypochlorous acid is suggested, which consequently oxidizes the alcohol through

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• ]. Further O-MTs can be classified based on a common acceptor group of modification, namely C-terminal carboxy-MTs and peptide/protein ʟ-aspartyl O-MTs (PAMTs). C-terminal carboxymethyltransferases Carboxy-MTs catalyse the formation of a methyl ester by methylating the oxygen atom within the hydroxy group of

• installed by the MT PoyE. Interestingly, two of these methylated asparagine residues also carry a hydroxy group at the β-carbon, which does not appear to affect the methylations. Renevey and Riniker demonstrated that the N-methylated asparagine residues of polytheonamide B are essential for the stability of

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• . Their structures differ from common parabens by the presence of an acetamide group ortho to the phenolic hydroxy group [14]. They exhibited weak activity against E. coli and methicillin-sensitive Staphylococcus aureus (MSSA). The three analogues 15–17 (Figure 6) with different ester chain lengths were

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• -fluoroalkylamines and the respective cations [6]. Intramolecular hydrogen bonds involving either the carboxy or hydroxy group of 4R- and 4S-hydroxyproline have been identified as key factors in stabilizing the favored conformations in the gas phase. Therein, the contribution of a gauche effect due to electron

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• commercially available p,p’-dihydroxyazobenzene (6), by using our recently developed DMC (2-chloro-1,3-dimethylimidazolinium chloride)-mediated one-pot glycosylation method in water [28], followed by O-alkylation of the remaining hydroxy group with BrCH2CH2NHBoc and acidic deprotection (Scheme 1). Three

• formation of the 1,2-anhydro sugar through intramolecular attack of the 2-hydroxy group of the DMC-activated β-intermediate, followed by dihydroxyazobenzene attacking the anomeric center in an SN2 manner, or by direct nucleophilic SN2 attack on the DMC-activated α-intermediate, to produce the corresponding

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• -DH-KR-ACP), and δ-module (KS-AT-DH-ER-KR-ACP) based on their domain composition regardless of the domain activity [2] (Figure 1a). While the stereoselectivity of a KR in a β-module can be directly inferred from the product hydroxy group, the stereochemical outcome of a KR from a γ- and δ-module is

• stereoselectivity of a KR. Such promiscuity can also be observed in the MycA KR in mycolactone biosynthesis, which accepts both α-substituted and α-unsubstituted substrates while retaining the same stereoselectivity for the β-hydroxy group [28]. To further investigate the sequence features of each module type, we

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• rearrangement (27.7 kcal mol−1; Figure S12, Supporting Information File 1) of uncharged 11 compared to that of 2 (Figure 3B). The free energy barrier value for 11 is likely too high to be non-enzymatic at 28 °C and may at least require deprotonation of the hydroxy group or at least H-bonding with solvent [23

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• (Scheme 9) [39]. The formation of the products can be explained by 1,4-addition of the terminal carbon of the diene to the chromone to give intermediate J and subsequent attack of the central carbon atom of the 1,3-dicarbonyl unit (aldol reaction). No aromatization and extrusion of the hydroxy group was

• ) [40]. The formation of the products can be explained by 1,4-addition of the terminal carbon of the diene to the chromone to give intermediate O and subsequent attack of the central carbon atom of the 1,3-dicarbonyl unit (aldol reaction). No aromatization and extrusion of the hydroxy group was observed

• these products can be explained by initial formation of the corresponding 2-(salicyloyl)furans V. Iodination of the latter afforded iodonium salt W which underwent cyclization by attack of the salicylate hydroxy group to give intermediate X. Extrusion of hydrogen iodide afforded the final product

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• [25]. On the other hand, the origin of 1, spontaneously derived from 8 under aerobic conditions, raises uncertainties about the actual production in vivo. Furthermore, the significance of the C12 hydroxy group in the hydroquinone intermediate 11 is evident in subsequent reactions, including the

• formation of a hemiacetal intermediate in gilvocarcin biosynthesis [9][38][39] and the AlpH-catalyzed ʟ-glutamylhydrazine adduct formation [14]. Notably, this C12 hydroxy group is absent in the quinone intermediate 3 of the cofactor-dependent pathway. Collectively, these observations suggest that the

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• below. This analysis allows us to understand the correlation between the stability of hedycaryols and the C+···OH distances, as this descriptor presents the difference in stability trends between hedycaryol and germacrene A cations, which is due to the hydroxy group in hedycaryol cations. where ΔΔEHed

• more stable than the 5-7 bicyclic compounds. Although the stability trends among the germacrene A and hedycaryol derived cations are similar, some changes in these trends may be ascribed to the hydroxy group in hedycaryol carbocations, which can stabilize the cations via lone pair–cation interaction

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• well with flufuran (23), having a 92% conversion. The slightly lower conversion is most likely due to the loss of the hydroxy group at the four position and is not surprising as it aligns with the results of 3-furoic acid (14). After demonstrating the probe could undergo the Diels–Alder reaction with

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• ) species and the triple bond that promotes an intramolecular nucleophilic attack of the amino group giving a indolcyclopalladium species. This is followed by CO insertion and intramolecular nucleophilic displacement by the hydroxy group to give the indole–PdII-cycle derivate. The reaction ends with a

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• Abstract We confirm the previously revised stereochemistry of spiroviolene by X-ray crystallographically characterizing a hydrazone derivative of 9-oxospiroviolane, which is synthesized by hydroboration/oxidation of spiroviolene followed by oxidation of the resultant hydroxy group. An unexpected thermal

• hydroxy group, or a keto group) for further derivatization. Spiroviolene was not transformed when subjected to conditions for allylic oxidation (SeO2) even at elevated temperature [27], and the starting material was fully recovered. We have also tried hydroboration/oxidation conditions for transforming

• BH3·THF in THF, and heated at 60 °C for 3 days. After oxidative treatment of the resultant alkylborane products with NaOH/H2O2, we have obtained three derivatives 9–11 with one hydroxy group in 37%, 30% and 21% isolated yield, respectively, as well as recovery of 10% of the starting material. After

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• 3au and 3av were produced in 34% and 39% yields, respectively, in which methoxy and tert-butyl groups were located in the para position to the hydroxy group (Table 2, entries 20 and 21). In the case of 3al, the mono-arylation of naphthol generated 3al’ in 20% isolated yield, which is the reason for

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• . It is somewhat surprising that NnlA cannot degrade 2-NAE given its structural similarities with NNG. The structural difference between the two molecules is the replacement of the α-carboxylate of NNG with a hydroxy group in 2-NAE. While a decrease in substrate affinity might be expected, there was no

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• that the only difference between compounds 3 and 2 is the position of the hydroxy group [28]. Analyses of the NMR data of compound 4 concluded that it is an analogue of 2. In comparison with 2, compound 4 has a ketone carbonyl signal at δC 219.1 and we finally confirmed its structure by comparing it

• differences in 13C NMR (ΔδC = 3.3) (Figures S19–S25, Supporting Information File 1) [43]. Moreover, the key correlation observed between H5 and H7 in the ROESY spectrum provides additional support for the β-configuration of this hydroxy group (Figure S26 and Table S7 in Supporting Information File 1). These

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• , requiring four steps, coupled with the expense of the palladium catalyst. Interestingly, when the hydroxy group in L3 was protected, the chemoselectivity of the reaction was poor, resulting in a 1:2 mixture of the desired chloride and the corresponding terminal alkene. Liu and colleagues put forth the

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• -methylheptanoic acid moieties in 3–5 have the same absolute configurations as those of 1. In particular, the β-hydroxy group at the Asp residue is introduced by the hydroxylase domain (TauD) embedded in VarG. This type of hydroxylase reportedly generates ʟ-erythro-Hya, in agreement with the proposed structures of