Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• mobile phase contained approximately 2% triethylamine as a basic additive. However, it is also possible to use crude 7 in the subsequent cyclization step without significantly affecting isolated yields. 1H NMR analysis showed that 7 was formed as a single geometrical isomer; although the imine

• system found in this natural product. However, we were intrigued that a competing cyclization process also formed isomeric lactones 9 and 10 in 8% yield and 11% yield, respectively. 1H NMR analysis confirmed that compounds 9 and 10 were both trans-fused 6/5 bicycles based on the magnitude of the vicinal

• of the 3-azabicyclo[3.3.1]nonane ring system. In any case, this aza-Prins reaction is by far the preferred mode of cyclization of iminium ion 12 based on the isolated yield of 8 (64%), ultimately leading to the carbon skeleton found in the natural product halichonic acid ((+)-1). In conformer 12b

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• were reported [30][31] and more recently, Carreira and co-workers reported [32] the first total synthesis of aberrarone through an impressive cascade reaction including a gold-catalyzed Nazarov cyclization, a cyclopropanation followed by intramolecular aldol reaction to forge the A, B and D rings

• one quaternary carbon stereocenter and 1,2-dikeone moiety, Nazarov cyclization [33] of 7 was proposed for synthesizing this challenging moiety. The corresponding precursor cyclopentenone 8 may be prepared from alkynone 9 through a gold-catalyzed C–H insertion [34]. Alkynone 9 could be achieved through

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

• desired triamine 9. After cyclization of the resulting 4-ethoxy-2,3,6-triaminopyridine (9) with formic acid leading to ethyl-protected compound 10 and liberation of the O6 with hydrogen bromide, 1-deazaguanine (11) was formed in 2 to 4% overall yield (Scheme 2) [18]. The approach by Gorton and Shive

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• -acetalation and decarboxylative [3 + 2] cycloaddition is shown in Scheme 4. With the promotion of the protonic solvent EtOH, compound 3 (N,S-acetal) from the condensation of cysteine and an aldehyde reacts with a second equivalent of aldehyde followed by cyclization to generate thiazolooxazol-1-one I

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• ]. In 2010, Echavarren and co-worker completed the formal total synthesis via a Au(I)-catalyzed cyclization (Scheme 2c) [13]. In 2018, Pabbaraja and co-workers disclosed the synthesis of macarpine by constructing ring C through the domino Michael addition/SNAr reaction of nitromethane to an ynone

• the electron-donating phenyl ring enabled the coordination of the alkyne with the Au+ complex in the α-position, which promoted the silyl ether to attack the β-position of the alkyne to promote a 6-endo-dig cyclization. Next, compound 11 was subjected to a solution of tetrabutylammonium fluoride (TBAF

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

• ] and provides insights into the biosynthesis pathways of these peptides [14]. However, the biosynthetic gene clusters of compounds 1–4 remain unidentified. Therefore, the least sterically hindered amine, namely the amino group of glycine, was selected as a nucleophile of the cyclization reaction in

• with stereocontrol. Then, the peptide chain was elongated by Fmoc-based solid-phase peptide synthesis. Finally, the cyclization of the peptide chain followed by simultaneous cleavage of all protecting groups in the solution phase afforded target compound 1. The comparison of the chromatograms of

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• released from the dehydrogenation of 2-aminobenzyl alcohol/1-phenylethanol according to the previous literature [28]. Lastly, the desired product 3aa was obtained by the condensation and cyclization of the aldehyde 5 with acetophenone (6) under base conditions. The potential antimicrobial activity of the

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• benzimidoyl chloride from thioamides by desulfurization and chlorination, as well as its application to the synthesis of 2-substituted benzazoles. Keywords: benzazole; bismuth; cyclization; desulfurization; thioamide; Introduction In the production of pharmacologically active compounds, 2-substituted

• conventional methods; a notable alternative is the cyclodesulfurization, where intramolecular cyclization is combined with desulfurization from thioamide analogs such as thioureas, thiosemicarbazides, and dithiocarbamate salts under mild reaction conditions [10]. These synthesis methods are effective for

• reaction of o-alkoxythiobenzamides with iodine in the presence of sodium hydride as the base [11]. Sugita et al. reported an unstable iodoalkyne, pentafluoro(iodoethynyl)benzene, which catalyzed the cyclization of thioamides with 2-aminophenol [12]. These approaches have some drawbacks, such as low yields

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• cross-coupling [34] in excellent yield. Esterification of 6 with monomethyl H-phosphonate tert-butylamine salt [35] resulted in the mixed H-phosphonate ester 7 in excellent yield. Cyclization using our homolytic aromatic substitution methodology [36] gave P-heterocycle 8 in modest yield. Other methods

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• capsule can catalyze the cyclization of (S)-citronellal forming isopulegol. In this study it was exploited the ability of the resorcinarene capsule to work as a Brønsted acid catalyst, and its aptitude to stabilize cationic intermediates and transition states inside the cavity. Velmurugan, Hu and co

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• cyclization of the corresponding tris-hydrazones, as well as the assembly of unsymmetrically substituted TAADs having both amino(amido) and hydroxy groups at bridge nitrogen atoms (2N,1O-TAADs and 1N,2O-TAADs) via a hitherto unknown co-trimerization of oxime and hydrazone units [35]. Also, structural studies

• derivatives involves the intramolecular cyclotrimerization of C=N bonds in a suitable trisimine precursor (Scheme 1). Previously, 3O-TAADs 2 were prepared by cyclization of corresponding trisoximes 1 [21]. However, this reaction is slow and reversible (upon heating adamantane structure 2 reverts to the tris

• -oxime form 1). Previous experimental and computational data evidence that cyclotrimerization of hydrazone groups proceeds more readily compared to oximes [18]. Hence, hydrazones 3 were expected to cyclize to corresponding TAADs 4 with high efficiency. On the other hand, cyclization of mixed oxime

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• Talaromyces wortmannii ATCC 26942. Heterologous expression reveals that TadA catalyzes the formation of a new fusicoccane-type diterpene talaro-7,13-diene. D2O isotope labeling combined with site-directed mutagenesis indicates that TadA might employ a different C2,6 cyclization strategy from the known

• synthases in pursuit of new terpenoids [15][16][17]. It is generally accepted that the FC-type diterpene skeleton is formed from geranylgeranyl diphosphate (GGPP) via a concerted C1,11–C10,14-bicyclization, followed by a C2,6-cyclization [18][19][20][21]. Theoretically, according to the configuration of

• stereogenic centers at C2, C6, C10, and C14 introduced during the two cyclization steps, FC-type diterpene synthases (DTSs) could be divided into 16 subtypes [20]. Furthermore, considering the modes of potential carbocation rearrangement and final carbocation quenching, there might be more FC-type DTSs in

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

• )-mediated cyclization. Neither of the reported spectral data for dihydrorosefuran match those of the synthetic product, suggesting that the isolated compound from Tagetes mendocina is in fact the natural product rosiridol, while the real structure of the product from Artemisia pallens remains unknown

• . Keywords: Ag(I) cyclization; allenylation; CpTiCl2; 2,5-dihydrofurans; monoterpenes; Introduction Artemisia pallens is an aromatic plant from southern India whose essential oil, known as Davana oil, has shown increasing interest mainly for its use in some beverages, cakes, pastries, etc., as well as in

• transformed into alcohol 6 through a simple change in the order of the reactions: addition of methylmagnesium bromide to 5 afforded 7, which was then transformed into 6 by the Ag(I)-mediated cyclization (Scheme 2). Once we had synthesized racemic compound 1, we designed a chiral version using a

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• debenzylation/cyclization of benzyldimethysilyl-substituted allylic alcohols [32]. To that end, carbinol 4c was treated with TBAF⋅3H2O (1.0 equiv), which resulted in the formation of 16 in 86% yield (along with toluene, Scheme 6). Alike 5-membered cyclic dimethyl(alkenyl)siloxanes, 16 was found to be highly

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• ketones and thiourea via an oxidative cyclization initiated by a radical process and a following condensation reaction (Scheme 1c) [29]. Although these methods are practical, most of these strategies require stoichiometric or excess amounts of halogenating reagents or oxidants, which are toxic, hazardous

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• ]. DMP oxidation of α-hydroxyester 21 and subsequent cycloisomerization led to the desired cyclization product 23 via transition state II in a dr of 5:1. Final deprotection gave preussochromone A (24). (−)-Preussochromone D A similar approach was chosen in the synthesis of the structurally related

• precursor for an intramolecular Friedel–Crafts cyclization (Scheme 9) [24]. Therefore, phenylacetaldehyde 52 was converted to the alcohol 53, which was esterified with the α-ketoacid 54 to give ketoester 55. Grignard addition to the keto carbonyl and subsequent TBS deprotection delivered the tertiary

• thermodynamically controlled basic intramolecular aldol addition of compound 108 using the bulky amine base 2,6-di-tert-butyl-4-methylpyridine (DTBMP) led to epimerization of the methyl group and cyclization, giving preussochromone F (109) as single isolable diastereomer probably via transition state XII. The

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• a collision between the ball and a particle of a chitin sample and (b) mechanical treatment of a particle of a lignin sample in a ring-and-puck mill. (a) Ultrasound-induced ATRP using piezoelectric BaTiO3 and (b) mechanochemical atom transfer radical cyclization (ATRC) using BaTiO3 by ball milling

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• -3(4H)-ones were also prepared by cyclization of 1,2-diaryldisulfanes with dialkyl but-2-ynedioates [24][25]. N-Substituted benzo-1,4-thiazine-2-carboxylates 4 (Figure 1) were prepared by m-CPBA-mediated oxidative ring expansion of substituted benzothiazoles [26], or via copper-catalyzed

• tested (see Supporting Information File 1). Next, compounds 17a and 17b were brominated in the α-position using Br2 under acidic conditions. Finally, cyclization reaction with 2-aminothiophenol (8a) in dry diethyl ether at 0 °C gave benzo-1,4-thiazines 19a and 19b in good yield. Interestingly, the

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• reactions with electrophiles, intramolecular cyclization and disproportionation process. The synthetic viability of the approach will be considered. A one-pot multistep synthetic protocol is suggested, based on addition of thiols to the mixture of isomeric alkenes formed in an electroreductive opening of a

• dominant reaction product formed in the reductive opening of the cyclopropane ring in complex 3 was new derivative 5 containing a five-membered ring (see below and Scheme 2). Intramolecular cyclization The anionic species formed in the ring opening in complex 3 undergo fast intramolecular cyclization via

• ). Notably, insertion of the second COOR group in the starting cyclopropane complex 4 completely suppresses this reaction channel: intramolecular cyclization of the anions formed in the reductive cleavage of the three-membered ring was not observed. This may be attributed to the decreased nucleophilicity as

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• ]. Intermediate A may combine with 1 to produce B, which may react with the EGB or another molecule A to produce C, releasing HCl. In Abushanab’s report [12], C can be coupled with A in a similar manner to yield D [12]. Finally, intramolecular cyclization of D may yield 2. In order to obtain a deeper insight in

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• first reported synthesis of pharmacologically interesting N-thiazolyl derivatives. Keywords: fused-ring systems; hydrazones; indazoles; intramolecular cyclization; N-heterocycles; Introduction 1H-Indazoles are important scaffolds due to the prevalence in compounds with biological activity [1], such as

• material for the synthesis of N-phenyl-1H-indazoles if the reaction conditions are carefully chosen. In addition, another target of the work was the application of the optimized reaction conditions to the cyclization of thiazolylhydrazones, aiming for the synthesis of novel N-thiazolyl-1H-indazoles

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

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

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• cinnamaldehyde gave no desired product (11t–v). Quite surprisingly, the Schiff base derived from methyl o-formylbenzoate also gave no desired product while cyclization led to isobenzofuran-1(3H)-one 14 (Scheme 1). Having secured a supply of diversely substituted 3(2H)-isoquinolones 11a–s, we proceeded to

Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544

• Yin Chen,
• Jinqiu Ren,
• Ruimin Yang,
• Jie Li,
• Sheng-Xiong Huang and
• Yijun Yan

Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101

• condensation between two molecules of α-keto acid. Structurally diverse p-terphenyls are formed from these key intermediates by several tailoring reactions such as cyclization, tautomerization, methylation, and glycosylation. A previous study has shown that the formation of 2,5-diarylcyclopentenone proceeds

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• pyrophosphate (FPP), and geranylgeranyl pyrophosphate (GGPP), to produce mono-, sesqui-, and diterpenes, respectively. The formation of terpenes relies on an assortment of carbocation steps like cyclization, methyl migrations, rearrangements, proton or hydride transfers, hydroxylations, and epoxidations. TPS

• main GGPP cyclization products, along with two minor compounds, namely the isoelisabethatrienes (IEs) A (13%) and B (9%), respectively. Interestingly, the elisabethatriene diterpene macrocycle and its isoforms can act as biosynthetic precursors of the bioactive compounds erogorgiaene and pseudopterosin

• ) proceed from the same substrate (GGPP) with an initial C1–C10 cyclization. In other TPS enzymes, the initial fold of GGPP in the active site can result in different initial cyclization, for example C1–C6, C1–C7, C1–C10, C1–C11, C1–C14, and C1–C15. The main difference between the two pathways to HP and IE

Electroreductive coupling of 2-acylbenzoates with α,β-unsaturated carbonyl compounds: density functional theory study on product selectivity

• Naoki Kise and
• Toshihiko Sakurai

Beilstein J. Org. Chem. 2022, 18, 956–962, doi:10.3762/bjoc.18.95

• 2 and subsequent rearrangement to 3 are also discussed. In particular, the latter mechanism was studied using density functional theory (DFT) calculations and it was suggested that the ΔG for the cyclization step of an intermediate enolate anion determines the product selectivity. Results and

• treatment with 1 M HCl produces phthalide 4 through desilylation and following lactonization of F (path d). As can be seen from Scheme 5, the cyclization of D to E is the key step for the formation of compound 6. Therefore, we calculated the intermediates (D and E) and transition states (D–E TS) for this

• the product ratio of 4:3 from the experimental results (Table 1, entries 1–6) were in good agreement. Therefore, it is presumed that whether the cyclization from D to E proceeds is thermodynamically controlled. Namely, when ∆G is large and negative, product 3 is selectively formed (Table 4, entries 1