Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• produce IPP and DMAPP [19][20][21]. Notably, this pathway successfully bypassed the limitations of native isoprenoid biosynthetic pathways, resulting in the overproduction of multiple (mero)terpenoids such as lycopene, cis-abienol, and prenylated tryptophan [15][19][22][23]. The clerodane and ent-kaurane

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• antiparallel arrangement of mirror image molecules held together via two hydrogen bonds in the crystal lattice of dimer 2. Keywords: cis/trans isomerism; peptoid; structure; trans-inducing side chain; Introduction The term “peptoids” refers to the family of artificial oligo(poly)mers consisting of N

• -supported combinatorial approaches [11][12][13]. The most relevant comparison of peptoids with peptides is in fact with polyprolines due to the presence of backbone tertiary amide linkages, much more prone to cis/trans equilibria than secondary amides. Indeed, in proteins, cis-amide bonds are most often

• observed for Xaa–Pro amide bonds and polyproline chains can adopt either the all-trans type II (PPII) or the all-cis type I (PPI) helical conformations, the latter being only observed in alcohol-type solvents [14]. In contrast to the prolyl-amide bond in acyclic peptides (≈5% of cis-Pro) [15], the cis

Thiophene/selenophene-based S-shaped double helicenes: regioselective synthesis and structures

• Mengjie Wang,
• Lanping Dang,
• Wan Xu,
• Zhiying Ma,
• Liuliu Shao,
• Guangxia Wang,
• Chunli Li and
• Hua Wang

Beilstein J. Org. Chem. 2022, 18, 809–817, doi:10.3762/bjoc.18.81

• sulfur atoms on the same side is defined as bb by us. The double Wittig reaction of 4a and 4b with 1,3-phenyldimethyltriphenylphosphonium bromide afforded compounds 5a and 5b with yields of 46% and 64%, respectively. After the double Wittig reaction of 4c we obtained a mixture of cis and trans isomers of

• 5c with the total yield of 50%. According to the results of 1H NMR the ratio of cis and trans isomers was approximately 1:0.25 (Scheme 1). Compounds 5 had five isomers and three reaction sites (2, 4, and 6-positions in the benzene moiety) during oxidative photocyclization. Irradiation of 5a–c

• . Mixture of cis and trans isomers 5c: yellow solid in yield of 50% (24.4 mg); mp > 300 °C; 1H NMR (400 MHz, CDCl3) δ (ppm): 7.76 (s, trans-), 7.73 (s, cis- and trans-), 7.72 (s, cis- and trans-), 7.57 (s, cis- and trans-), 7.56 (s, trans-), 7.49–7.33 (m, trans-, cis- and trans-), 7.30 (d, J = 16.0 Hz, cis

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• ’, 1j’ were successfully isolated and fully characterized. Notably, the relative configuration of major isomer 1f (CCDC 2109575) was determined by X-ray crystallographic analysis, in which the m-chlorophenyl, benzoyl and the phenyl group in oxindole are in cis-configuration. It has been known that the

• benzoyl group and the phenyl group in oxindole stand in cis-position in the starting 3-phenacylideneoxindoles [75]. Therefore, a concerted Diels–Alder reaction should be involved in this three-component reaction. On the basis of this success, we further considered whether other dienophiles could be

• ’ and 2g’ were also isolated and fully characterized. Moreover, the relative configuration of major isomer 2b (CCDC 2109576) and minor isomer 2g’ (CCDC 2109577) were determined by X-ray crystallographic analysis. In the major isomer 2b, the phenyl group at C4-position is in cis-position to the aryl

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• reductive amination/cyclization of enantiopure cis-cyclopropane dicarbonyls [26]. The strategy based on azomethine ylide cycloadditions to cyclopropenes enables ready access to a wide range of spiro-fused 3-azabicyclo[3.1.0]hexanes (Scheme 1a). Inspired by our recent achievements, we have focused on

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• acetate (54) is sold as a mixture of the cis- and the trans-isomer. Interestingly, the cis-isomer of 54 has a “pronounced fruity note over the woody sweetness”, while the trans-isomer is weaker having a “dry, leathery” scent [9]. The commonly used concentration of woody acetate (54) in a perfume is 3–10

• %. Thus, Brenna and co-workers developed a cis-selective synthesis of 54 via a biocatalytic process in flow (Scheme 12) [45]. In the first step, a mixture of cyclohexanone 51, NADH, and isopropanol in an aqueous phosphate buffer (pH ≈ 7) is pumped through a continuously stirred membrane reactor at 30 °C

• with a residence time of 1 h containing alcohol dehydrogenase (ADH200). In this process, cyclohexanone 51 is selectively reduced to the corresponding cis-alcohol 52 and subsequently mixed with n-hexane providing a biphasic mixture which is continuously separated in a membrane separator. The organic

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

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

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• aryl group exist on the cis-position of the carbonyl group on the exocyclic C=C bond (Z-configuration). Thus, it can be concluded that the major isomers 3a–z have this kind of the relative configuration. In Figure 3, the aryl group and the carbonyl group of the oxindole scaffold also exist on trans

• -position in the newly formed cyclohexyl ring, while an E-configuration was observed for the exocyclic C=C double bond. Therefore, the major and minor isomers were actually attributable to the Z/E-configuration of the C=C bond, not to the cis/trans-positions in the newly formed cyclohexyl ring. In order to

New synthesis of a late-stage tetracyclic key intermediate of lumateperone

• Mátyás Milen,
• Bálint Nyulasi,
• Tamás Nagy,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2022, 18, 653–659, doi:10.3762/bjoc.18.66

• to the hydrazine derivative 4, followed by a Fischer indole synthesis with ethyl 4-oxopiperidine-1-carboxylate (5) provided tetracyclic compound 6. Its reduction with sodium cyanoborohydride in trifluoroacetic acid (TFA) to cis-indoline derivative (±)-7, followed by N-methylation [(±)-8] and

• with triethylsilane in TFA to cis-racemate 15. The key step of the syntheses is the resolution of this intermediate with (R)-mandelic acid. The enantiomerically pure (R)-mandelate salt 16 thus obtained was reacted with ethyl chloroformate to give 17. It was then transformed to tetracyclic derivative 8

• reduced with sodium cyanoborohydride in acetic acid to cis-indoline derivative (±)-35. Removal of the trifluoroacetyl group to (±)-36 followed by N-methylation with formaldehyde and sodium cyanoborohydride gave target compound (±)-9a. It has to be mentioned that the preparation of compound 31 has been

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• . For this purpose, they have chosen the ditopic bisurea “strut” 12 (Figure 3), which generated a 2D discrete molecular triangle 14 in the presence of an equimolar amount of the cis-(tmen)Pd(NO3)2 acceptor 5 [59]. In order to prevent the urea moieties on the triangle to get engaged in intermolecular H

• -bonding, which would lead to catalytic quenching, a unique design strategy was applied. Instead of using a cis-blocked palladium(II) unit for self-assembly, Pd(NO3)2 was employed along with the triazole-based 0° clip 13. In a one-pot reaction, 12 and 13 in DMSO were treated with Pd(NO3)2 in a 1:1:1 ratio

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• diffraction analysis also revealed the presence of four chiral stereocenters with two oxindole moieties at 1,3-possition that are in trans orientation to the 2-benzoyl group and the 5-aryl group is in cis orientation (Figure 2). This observation proved that the most thermodynamically stable diastereomer was

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• alkenyl site, producing the final 1,2-reduction product cis-O-hydroxycinnamyl alcohol 19. As a comparison, in the absence of the β-cyclodextrin host, both the 1,2- and 1,4-reduction products were observed. X-ray crystallography determined the host–guest complex of the coumarin and β-cyclodextrin, which

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• electronic nature. Environment-friendly reaction conditions, easily accessible substrates, and broad substrate scope highlight the practicality of this methodology. Results of the acid-catalyzed intramolecular hydroindolation of cis-β-(α′,α′-dimethyl)-4′-methindolylstyrenes 17 were reported by Stokes and co

• [4,3,2-cd]indoles via indole C3 regioselective aza-Michael addition/cyclization/dehydration sequence. Indole C3 regioselective Pictet−Spengler reaction of 2-(1H-indol-4-yl)ethanamines. Indole C3 regioselective hydroindolation of cis-β-(α′,α′-dimethyl)-4′-methindolylstyrenes. Indole C3 regioselective

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• uniquely, both of the olefinic proton resonances (H12 and H13) were broadened at 25 °C (Figure 3a). However, upon heating to 50 °C, H12 split into doublet-triplet, which allowed the extraction of 3JH12,H13 = 11.4 Hz to deduce a cis configuration. H13, in contrast, broadened more severely at the raised

• carbons (C10: δC 130.2; C11: δC 128.9), revealing the site of unsaturation at a γ,δ-position (Figure 2 and Table 2). The double bond geometry was determined to be cis on the basis of the chemical shifts of the allylic carbons (C12: δC 22.3, C9: δC 26.6) [25], which are closer to those of a (Z)-isomer (δC

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• , Hacettepe University, 06800 Ankara, Turkey 10.3762/bjoc.18.7 Abstract The first synthesis of 2-amino-3,4-dihydroxycyclooctane-1-carboxylic acid, methyl 6-hydroxy-9-oxo-8-oxabicyclo[5.2.1]decan-10-yl)carbamate, and 10-amino-6-hydroxy-8-oxabicyclo[5.2.1]decan-9-one starting from cis-9-azabicyclo[6.2.0]dec-6

• -en-10-one is described. cis-9-Azabicyclo[6.2.0]dec-6-en-10-one was transformed into the corresponding amino ester and its protected amine. Oxidation of the double bond in the N-Boc-protected methyl 2-aminocyclooct-3-ene-1-carboxylate then delivered the targeted amino acid and its derivatives. Density

• . We have recently reported the synthesis of various eight-membered aminocyclitols and their derivatives [19][20][21][22][23][24][25]. In the present paper, we describe the synthesis of some hydroxylated β-amino acid derivatives containing eight-membered rings starting from cis,cis-1,3-cyclooctadiene

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• diastereomers, i.e. cis/trans isomers or conformers with a high interconversion barrier. For complestatin-based macrocyclic peptides, the existence of biaryl atropisomers caused by the indole of tryptophan has been reported [82]. Recently, the occurrence of isomers was also observed in our group for SMC

• macrocycle. The amide bond in the staple of P5 is connected to two flexible aliphatic chains and may exist in cis and trans configuration. The energy difference in the analogue N-methylacetamide (NMA) favours the trans isomer by about 2.3 kcal mol−1, which corresponds to an expected cis/trans ratio of about

• cis and trans isomers compared to isolated NMA. The presence of diastereomers in the peptide bonds is less likely since the cis/trans ratio in polypeptides is lower than 1:820 (i.e., an energy difference greater than 4.0 kcal mol−1 in favour of the trans isomer) [84]. It is, however, currently

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• co-workers established a Heck/Kumada cross-coupling cascade to construct nitrogen and oxygen-containing cis-heterospirocycles 40 in high yield and diastereoselectivity with inexpensive Fe(acac)3 as the precatalyst (Scheme 8) [73]. Interestingly, this protocol was applicable to substrates bearing

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• successfully performed using the corresponding acetate salt in methanol at rt for 48 h, affording cis-L1-M, L2-M, and L3-M in yields depicted in Scheme 1. The relative configuration was unambiguously determined by comparison of their corresponding 1H NMR with the reported similar 1H NMR with other metals, and

• the cis-configuration determined according to X-ray diffraction patterns observed in precedent works [15][16]. Although a structural motif of the metallosurfactants is having a long alkyl chain (hydrophobic part), in these cases, L1–L3 possessed four hydrophobic domains, which are responsible of the

• conformations analyzed by the 1H NMR spectra of nickel and palladium complexes, presumably correlated with their activity. According to the previous activities of derivatives of this nature [15][16] the cis-complex was identified as the therapeutic arrow. We initially tried to determine the driving force

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

• -catalyzed hydrolysis of 10 with concentrated hydrochloric acid in acetone/water afforded diol 3 in excellent 93% yield. The crystallization of the crude product from a hexanes/CH2Cl2 mixture led to the preferential formation of the thermodynamically more stable 4,5-cis isomer (determined on the basis of a

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

• derivative 11 was obtained by cyclization with 3 equivalents of potassium O-ethyl xanthate. It was then treated with a methanolic ammonia solution to give triol compound 12. The protection of the cis-2,3-vicinal hydroxy groups of 12 with an isopropylidene, followed by benzoylation, gave compound 13. Using 2

• ). Sodium periodate was used for oxidative cleavage of cis-diol 3d. The subsequent aldehyde was then converted to a vicinal diol by reduction with sodium borohydride. Further, it was protected by 2,2-dimethoxypropane to give the 1,3-oxathiolane derivative 21. The benzoylated compound 22 was obtained by

• hydroxyoxathiolane 32. Further, acetylation of the hydroxyoxathiolane in the presence of methanesulfonic acid gave a 1:2 mixture of the trans-diastereomer 33 and the cis-diastereomer 34. The esterification using ʟ-menthol as a chiral auxiliary resulted in a diastereomeric mixture, which was successfully

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• trans-oriented. Additionally, the phenyl group is cis-oriented to the 1-benzylpyrrolidine-2,5-dione ring in compound 3a. On the other hand, for compound 3b (Figure 3), it can be seen that the phenyl group is trans-oriented to both, the p-chlorobenzoyl group and the 1-benzylpyrrolidine-2,5-dione ring in

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• two separate publications [36][37]. The cyclized product thus formed was further treated with iodine to get trans-2,5-bis(iodomethyl)-p-dioxane (4a). The formation of trans-isomer 4a as the major product and cis-isomer 4b as a minor product was later confirmed by Summerbell et al. by repeating the

• ratio of diastereomeric products [39]. Later, Summerbell and co-workers modified the reaction conditions to synthesize 2,6-disubstituted dioxane derivatives 6 (cis/trans 16:1). Unlike 2,5-disubstituted dioxane derivatives, here the cis-isomer was the major product. A higher ratio of the cis-dioxane 6

• the selective formation of diastereomeric products. They also observed that changes in Hg(II) salts result in different ratios of the cis- and trans-isomer in the cyclized products [47]. The differences in cis and trans ratios were primarily due to the basicity of anions associated with Hg(II) salts

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• relatively large coupling constant (8.8 Hz) between H-7 and H-8 in 2, as opposed to the relatively small coupling constant (6.1 Hz) between H-7 and H-8 in 1, verified that H-7 and H-8 are cis-oriented [10][16], which was supported by the NOESY correlations of H-7/H-8, H-2/H-9, and H-6/H-9 (Figure 2). The ECD

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• groups (Table 1). COSY analysis clarified two carbon chains (Figure 2). The first one, spanning from H7 to H17, contained an oxymethine (H9) branching at C10, a cis-configured double bond between C11 and C12 (3JH11,H12 = 10.0 Hz), and a trans-double bond between C15 and C16 (3JH15,H16 = 14.8 Hz

• -cis configuration of the diene moiety was indicated by a NOESY correlation between H21 and H27. The absolute configuration of the dehydrodecalin moiety of 3 was tentatively assigned to be identical with 4 because 3 was considered as a biosynthetic precursor of 4 [20]. Compounds 1‒3 showed

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• recognition by plant cell-wall antibodies. To avoid performing the challenging 1,2-cis glycosylation that would generate a mixture of anomers in AGA, the α(1–6) linkage between glucose and xylose was pre-installed in the disaccharide BB 16 (Scheme 3, highlighted in red) [104]. The orthogonal levulinoyl (Lev

• solution phase using block coupling [165]. α-Glucans In contrast to the relatively simple formation of a 1,2-trans glycosidic bond using participating group at C-2, the construction of 1,2-cis glycosidic bonds is a long-standing challenge in the field of glycochemistry [167]. The formation of 1,2-cis Glc

• linkages is particularly relevant, as α(1–4)-glucans form the backbone of starch, with the linear amylose and the branched amylopectin, and α(1–3)-glucans are related to fungal pathogenicity in plants [168]. Only few options can aid the stereoselective construction of 1,2-cis glycosidic bonds. In general

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• helped to elucidate the operative mechanism of the hydroalkylation (Scheme 3) [29]. The outer-sphere attack of the enolic carbon on the complexed metal–olefin double bond was evidenced by the cyclization of (E)-1d-7,8-d2, which furnished exclusively the compound cis-2d-3,4-d2 after the protonolysis of