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

• with a known congener, nomimicin A (4), from Actinomadura sp. AKA43. Compounds 1 and 2 are new members of the spirotetronate-class antibiotics, characterized by a macrocyclic structure containing a trans-decalin unit and a tetronic acid moiety spiro-linked with a cyclohexene ring. To date, more than

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• intermediate and the coumarin through hydrogen bonding, as shown in Scheme 25. An enantioselective one-pot synthesis of spiro[dihydrofurocoumarin/pyrazolone] 83 mediated by quinine and squaramide catalyst 84 was reported by Xu et al. [61]. The work draws attention for the wide range of compounds obtained with

• /indandione-fused spirocyclopentanes 104 bearing four contiguous stereogenic centers, was described by Chen et al. [68]. This transformation was catalyzed by a cinchona-thiourea derivative 105 furnishing the spiro compounds with good to high yield and enantioselectivity (Scheme 33). In this method two

• -acylcoumarins 43 to 3-halooxindoles 74. Enantioselective synthesis of 3,4-dihydrocoumarins 78 catalyzed by squaramide 73. Organocatalyzed [4 + 2] cycloaddition between 2,4-dienals 79 and 3-coumarincarboxylates 43. Enantioselective one-pot Michael addition/intramolecular cyclization for the synthesis of spiro

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

•  34B and 34C) [170]. The new method presented broad scope in the construction of tetrasubstituted carbon centers from methylenes to access a wide range of spiro N-heterocyclic oxindoles in excellent yields, including diamine, benzamide, and spirothiazole scaffolds. The high potential of the reaction

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• mellonella [66]. Fumitremorgins The class of fumitremorgins comprises several diketopiperazine alkaloids which are tremorgenic mycotoxins. However, there are several fumitremorgin-like indole alkaloids including tryprostatins, spiro- and cyclotryprostatins and verruculogen besides fumitremorgins themselves

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• )-27-6. Enantioselective fluorinations of typical enolates were then performed (Scheme 63). The (R)-27-6 reagent gave up to 79% yield and 88% enantiomeric excess in the case of 2-benzyl-α-tetralone. 1-28. (R)- and (S)-N-fluoro-3-tert-butyl-7-nitro-benzothiazine 1,1-dioxides and spiro-type analogues In

• ketones, as is illustrated with representative in Scheme 65. In addition, the Takeuchi group reported a spiro-type analogue, (2'S,3R,5'R)-2-fluoro-2'-methylethyl-5'-methyl-2H,4H-spiro[benzo[e][1,2]thiazine-3,1'-cyclohexane]-1,1-dione (28-7a) [94], as their third chiral reagent in this sultam series. As

• can be seen in Scheme 66, 28-4 was treated with BuLi followed by reaction with optically active menthone to give 28-5, which was converted to enantiomers of spiro sultams 28-6a and 28-6b in high yield. The spiro sultams 28-6a and -6b were separated and each was fluorinated with FClO3 to give (2'S,3R,5

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

• cascade aza-Michael addition/olefin hydroalkylation reaction between N-tosylallylamines and α,β-unsaturated ketones using a catalytic system of a gold(I) complex and a silver salt [45]. The spiro compound 25, which was obtained in moderate yield and with poor diastereoselectivity after a 20 h reaction

• in Fe(III)-promoted hydroalkylation/cyclization cascades (Scheme 26A) [93]. Here, the carbocyclization occurred via a SN2 mechanism between the enolate intermediate and the tethered halide (Scheme 26B). Using arylidene diones 67 as radical acceptors, spiro compounds 69 were obtained in moderate to

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• the stereoselective synthesis of spiro β-lactam 57 from chiral (RS)-N-tert-butanesulfinyl isatin ketimine 53 (R1 = H), with a bulky trityl protecting group bonded to the nitrogen indolic atom (Tr = triphenylmethyl), and ethyl bromoacetate. The Zn/Cu-mediated Reformatsky-type reaction furnished

• the synthesis of (–)-AG-041R, a gastrin/cholecyctokinin-B receptor antagonist. In addition, amino ester 55 was transformed into the fully unprotected amino acid 56 under basic conditions in MeOH, and after that, further treatment with of MsCl and NaHCO3 in MeCN at 80 °C led to spiro-β-lactam

• proceeded with high levels of diastereocontrol. The resulting sulfonamide derivatives 95 were transformed into the target spiro compound 97 by performing successive desulfinylation and intramolecular palladium-catalyzed N-arylation. To rationalize the stereochemical course of the addition, DFT calculations

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• NMR and X-ray spectroscopic techniques. The regioisomeric spiro-oxazolidin-2-one was prepared in a similar way starting from the commercially available (1R)-(−)-myrtenol (10). The reduction or alkaline hydrolysis of the oxazolidines, followed by reductive alkylation resulted in primary and secondary 2

• (Figure 2). To synthesize the regioisomeric spiro-oxazolidinone derivative 12, (1R)-(−)-myrtenol (10) was chosen as starting material (Scheme 2). The synthetic method was similar to that mentioned above for (−)-isopinocarveol. In the first step, carbamate 11 was prepared [37], then the aminohydroxylation

• was carried out catalyzed by potassium osmate(VI), which led to the formation of the spiro-oxazolidine-2-one 12 in a highly regio- and stereoselective manner. Based on the NMR spectroscopic measurements of the crude product, the spiro derivative 12 was obtained exclusively with the relative

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• ). The synthesis of indoline-spiro fused pyran derivatives 53 was reported by Jiang and co-workers [57] employing a multicomponent reaction between substituted isatins 35, cyclic 1,3-diketones 6 and malononitrile (51) in an aqueous medium without any catalyst. Reaction diversity was examined by using

• that employing indanedione as the cyclic diketone directed the formation of an aromatized molecule 139a instead of the expected spiro product. The authors rationalized 139a formation through a competitive intramolecular cyclo condensation over intermolecular cyclo condensation reaction with loss of

• B undergoes cyclocondensation to yield the spiro product 139, whereas for 139a intermediate B falls prey to intramolecular cyclo condensation (Scheme 54). The synthesis of regioselectively functionalized macrocyclane-fused pyrazolo[3,4-b]pyridine derivatives 142 was demonstrated by Jiang and co

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• that the reaction is broad in scope. Remarkably, C–S bonds and spiro compounds have been constructed simultaneously in this approach, which are promising for drug synthesis. Substrate 46 comprises both indole and alkynone groups, leading to light-promoted intramolecular electron transfer in order to

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• series of spiromethanofullerenes was synthesized using various diazo derivatives. For example, compounds spiro-bound with glycosides are the first chiral and enantiomerically pure derivatives of fullerenes 71 and 72 (Scheme 22) [107]. It should be noted that though a considerable amount of information on

• the synthesis of various spiromethanofullerenes. For example, spiro derivatives 73–75 were obtained in one of the first works on this subject (Figure 7). The authors obtained quinone-derived [6,6]-closed spiromethanofullerenes 76–78 by reactions of C60 with the corresponding diazo compounds upon

• heating, or photochemically in a nitrogen atmosphere (Scheme 23) [109]. The reaction of spiro[10-anthron-9,61'-methanofullerene] (79) [110] with bis(trimethylsilyl)carbodiimide and malononitrile in pyridine in the presence of TiCl4 resulted in spirocyclic blocks 80 and 81, respectively (Scheme 24) [111

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• dispersion effects are not included, whereas M062X includes nonlocal effects of electronic dispersion [70][75]. We also demonstrate the preparation of norbornene structures substituted at the methylene bridge. The reaction of model nitrostyrene 1h with spiro[2.4]hepta-4,6-diene was carried out (Scheme 2). As

• °C) and CHD at 110 °C. Scope of the nitrostyrenes 1 in the Diels–Alder reaction with CPD (dr = exo:endo). The Diels–Alder reaction of nitrostyrene 1h with spiro[2.4]hepta-4,6-diene. Diels–Alder reaction of nitrostyrenes 1 with CHD (dr = exo:endo). (а) Reaction under microwave activation. Kinetic

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• reagent was also used for the synthesis of organic spiro compounds, containing selectively fluorinated cyclopropanes 38a,b [45], for the preparation of 6,6-difluoro-3-azabicyclo[3.1.0]hexane (39) (on a 10 g scale) [46], and of the epothilone B analog 40 [47] (Table 2). The reagents (chlorodifluoromethyl

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• in natural product synthesis reported from 2011–2020 (inclusive). The intermolecular all-carbon [3 + 2] cycloaddition offers a facile approach to install functionalized five-carbon carbocycles, including fused-rings (e.g., longeracinphyllin A (10)) and/or spiro-ring (e.g., marcfortine B (8)), at

• enantioselective synthesis of marcfortine C (9, Scheme 4B). Another brilliant example is the development of a chiral-phosphine-catalyzed [3 + 2] annulation reported by Lu in 2019, in which the chiral phosphine catalyst confers high stereocontrol on the formation of a spiro adduct bearing two vicinal all-carbon

• product synthesis. (A) Synthesis of longeracinphyllin A (10) [41]. (B) Synthesis of daphenylline (11) [42]. (C) Synthesis of daphenylline (11) [43]. (A) Phosphine-catalyzed [3 + 2] annulation of unsymmetric isoindigo 100 with allene in the preparation of spiro adduct 103 [46]. (B) The proposed catalytic

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• -lactone derivatives spiro-fused to an oxindole (A), one of which exhibited a potent cytotoxic activity [9]. Our research group succeeded the enantiopure synthesis of these compounds, in which enantioselective allylation of an isatin derivative with an amido-functionalized allylstannane was employed as a

• key reaction (Scheme 1b) [10][11]. More recently, an amide-functionalized allyl boronate was developed as an alternative reagent for the allylstannane [12][13][14][15][16], which led to the syntheses of not only cytotoxic methylene-lactones spiro-fused to a lactam ring (B) but also their analogous

• the construction of the spiro skeleton of 4 and 5. For this purpose, we initially attempted to transform 3b to 5a through the reaction sequence consisting of copper-mediated hydroxylation and acid-mediated lactonization based on our previous reports [10][11][14][21]. Substitution of the phenylthio

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups

• Benjamin Jeffries,
• Zhong Wang,
• Robert I. Troup,
• Anaïs Goupille,
• Jean-Yves Le Questel,
• Charlene Fallan,
• James S. Scott,
• Elisabetta Chiarparin,
• Jérôme Graton and
• Bruno Linclau

Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182

• drugs with such substructures include Voxilaprevir and Glecaprevir. Finally, it is useful to consider the lipophilicity changes upon extending a propyl or ethyl chain to a cyclopropylmethyl moiety, which represents a one-carbon and a two-carbon extension, respectively. It is known that adding a spiro

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• -lactams [6], quinolin-5-ones [7], spirobisglutarimides [8], indolizines [9], and spiro carbocyclic frameworks [10]. However, most of the reported synthetic transformations utilize either allylic hydroxy-protected or allyl halide-substituted MBH adducts [11][12][13][14][15][16][17][18][19][20][21][22][23

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• , cyclopentanone, and three carbon ring-expanded 1,3-diones from vinyl spiro epoxides [14]. The reaction is initiated by the addition of a thiyl radical to the vinyl epoxide 24, followed by the epoxide fragmentation to the alkoxy radical 25. Then, the β-cleavage to form the carbon-centered radical 26, the final

• expansion of vinyl spiro epoxides. Disulfide-catalyzed aerobic oxidation of diarylacetylene. Disulfide-catalyzed aerobic photooxidative cleavage of olefins. Disulfide-catalyzed aerobic oxidation of 1,3-dicarbonyl compounds. Proposed mechanism of the disulfide-catalyzed aerobic oxidation of 1,3-dicarbonyl

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• intermediate for the total synthesis of sesquiterpene thioalkaloids (Scheme 3). Spiro[3.3]heptane derivatives were recently used as the surrogates of piperazines, piperidines, morpholines, and thiomorpholines, which display pharmacological activities [35]. 1,6-Thiazaspiro[3.3]heptane (24) was synthesized for

• series of thietanose nucleosides 118 [53]. Similarly, enatiomeric thietanose nucleosides 123 were prepared from L-xylose [53] (Scheme 24). In 2010, Takahata and co-workers designed and synthesized thietane-fused nucleosides. They first prepared a key intermediate spiro acetal 125, which was converted

[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

• Margareta Sohora,
• Leo Mandić and
• Nikola Basarić

Beilstein J. Org. Chem. 2020, 16, 1296–1304, doi:10.3762/bjoc.16.110

• , 1C), 30.1 (t, 1C), 26.2 (t, 1C), 23.7 (t, 1C), 21.3 (t, 1C); MS m/z (% relative intensity): 229 (100), 230 (15.1), 231 (1.1). 1,6-Dioxo-1,4,5,6-tetrahydro-2H-spiro[benzo[c]azocine-3,1'-cyclohexane]-5-carbonitrile (9): 3 mg (3%), oily crystals; 1H NMR (CD3OD, 300 MHz) δ 8.19-8.15 (m, 1H), 8.04–8.00 (m

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• to C-26 was then connected at C-20 by HMBC correlations from H3-39 to C-19, C-20, and C-21. The carbon chain was further extended from C-26, via the spiro carbon C-27 (δC 98.6) and a methylene C-29, to the terminal methyl C-34 on the basis of COSY and HMBC correlations. Finally, an HMBC correlation

• from the oxymethine H-25 to C-1 established a macrolactone structure, and a spiroacetal structure with two six-membered rings was deduced from a series of HMBC correlations of the protons in the spiro rings to C-27, illustrating the oligomycin-class structure. The remaining six carbons from C-42 to C

Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

• Phil M. Pithan,
• Sören Steup and
• Heiko Ihmels

Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82

• for the development of photochromic chemosensors that allow the colorimetric or fluorimetric detection of particular analytes [5][29][35][36][37][38][39][40][41]. Furthermore, studies of such spiro derivatives [16][42][43], specifically spiroindolinonaphthoxazines [44][45][46][47], have shown that the

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• imposed by the steroid skeleton on the dienyl tetrahydrofuran α-face, imposing orbital interactions with the dienophile from the β-face (Figure 3b). All these structures have an extended skeleton, with the steroid part being perpendicular to the cycloadduct moiety thanks to the spiro junction. Conclusion

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• installation of the1,3-diene units at the anomeric center of the future C-aryl glycoside (23) in high yields (94–98%, Scheme 24). Alternatively, an intramolecular enyne metathesis promoted by the first-generation Grubbs catalyst produced the spiro-C-aryl glycoside 24 from sugar enyne precursors (Scheme 25

• ). Subsequent Diels–Alder cycloaddition reactions with dienophiles and further aromatization reactions paved the way for a convenient access to structurally diverse polycyclic compounds. For instance, installing the C-aryl and spiro-C-aryl glycosides in the same moiety was successfully achieved. An application

• . Synthesis of spiro-C-aryl glycoside 24 by a tandem intramolecular enyne metathesis/Diels–Alder reaction/aromatization. Pathways to (−)-exiguolide (25) by Trost’s Ru-catalyzed enyne cross-coupling and cross-metathesis [94]. Funding Support from the Romanian Academy and from Wallonie-Bruxelles International