Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• potential anti-inflammatory activity. In this study, three new sulfur-containing spiroketals – breynin J (1), epibreynin J (2), and probreynogenin (3) – along with four known compounds – probreynin I (4), phyllaemblic acid (5), breynin B (6), and epibreynin B (7) – were isolated from the roots of Breynia

• Freund's adjuvant-induced arthritis in rats [12]. However, the molecular mechanisms of these anti-inflammatory effects have not been investigated. In our ongoing search for bioactive natural products, we have isolated three new spiroketals – breynin J (1), epibreynin J (2), and probreynogenin (3) – and

• four known spiroketals – probreynin I (4) [13], phyllaemblic acid (5) [10], breynin B (6) [2], and epibreynin B (7) [2] – from the roots of B. disticha, a species that has not previously been chemically investigated (Figure 1). Herein, we describe the isolation and structural elucidation of new

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

• reaction conditions leads to the formation of 2.5-disubstitued-furan 147 rather than mono-unsaturated spiroketals [100]. Interestingly when 1.4-dihydroxy-5-alkyne derivatives were subjected to a Hg(OTf)2-catalyzed cyclization then oxacyclization takes place to form tetrahydropyran derivatives (Scheme 43

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• generation of high-quality small molecule collections, taking advantage of the stereochemical diversity, and of their three-dimensional shape and structural bias to develop lead compounds, specifically in the field of protein–protein interactions [3][4][5][6]. Spiranic rings such as spiroketals are present

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• -substituted phenol 126 to tricyclic spiroketals 127a,b in 56% yield using PIDA (15) as electrophilic species in acetonitrile at room temperature (Scheme 47). The mixture of both isomers was separated by flash column chromatography and the stereochemistry of major isomer 127a was assigned on the basis of NOE

• precatalyst in iodine(III)-catalyzed enantioselective synthesis of spiroketals with high selectivities. In this report, substrates 128 were reacted with 10 mol % of chiral iodoarene 129a and 129b in the presence of mCPBA oxidant in chloroform at 0 °C. The desired ortho-spirocyclic ketals 130 were obtained in

• starting from substrate 147. (±)-Aculeatin and its derivatives possessing spirocyclic skeleton are known for their antibacterial and antiprotozoal properties [135]. In this report, substrate 147 was cyclized to spiroketals, i.e., (−)-aculeatin (146a) and (+)-146b in 3:2 ratio. Herein, 1.0 equivalent of

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• nitrile, along with trace amounts of product. Using 10 equiv of cyclohexane carbonitrile gave moderate yield of product 8a along with the formation of di-D-fructose dianhydride or spiroketals [49] as the side product. Finally, 15 equiv of nitrile served best for this transformation providing

• stereoselectively manner. Next, the reaction was carried out with electron-withdrawing groups containing aliphatic nitriles such as bromoacetonitrile, trichloroacetonitrile and malonitrile. However, in all the reactions, no product formation was observed, and instead, the reaction mixture gave spiroketals

• the nitrile group. In all the low yielding reactions, spiroketals are observed in 15–20% yield. This was evidenced by activating 3a and 5a with TMSOTf (1 equiv) in toluene in the absence of a nucleophile. While 3a gave a symmetric spiroketal 3ab with a single set of protons in 75% yield (Scheme 3

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• Park, Harlow, CM19 5AW, United Kingdom 10.3762/bjoc.11.157 Abstract Three novel spiroketals were prepared by a one-pot transformation of 6-O-methyl-9(E)-hydroxyiminoerythronolide A. We present the formation of a [4.5]spiroketal moiety within the macrolide lactone ring, but also the unexpected

• formation of a 10-C=11-C double bond and spontaneous change of stereochemistry at position 8-C. As a result, a thermodynamically stable structure was obtained. The structures of two new diastereomeric, unsaturated spiroketals, their configurations and conformations, were determined by means of NMR

• example, in cases of calyculin and okadaic acid it has been proposed [18][19] that the spiroketal unit acts as a β-turn mimic. Naturally occurring spiroketals exhibit a wide spectrum of biological activity: anticancer [20][21][22], antibiotic [23][24], antifungal [25], anthelmintic [26] and anti-HIV [27

Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• ; hydrozirconation; natural products; spiroketals; total synthesis; Findings Integramycin is a polyketide natural product isolated from Actinoplanes sp. by the Singh group at Merck [1] (Figure 1). The compound was found to inhibit HIV-1 integrase coupled strand transfer reactions with IC50 values of 3 and 4 μM

Thermochemistry and photochemistry of spiroketals derived from indan-2-one: Stepwise processes versus coarctate fragmentations

• Götz Bucher,
• Gernot Heitmann and
• Rainer Herges

Beilstein J. Org. Chem. 2013, 9, 1668–1676, doi:10.3762/bjoc.9.191

• with predictions, spiroketals derived from indan-2-one undergo photochemical coarctate fragmentation, if both terminators are 5-membered rings, and thermal coarctate fragmentation, if both a 5-ring and a 7-ring terminator are present. In the latter case, the experimental evidence suggests that the

• K. Infrared spectrum obtained upon FVP of 3 at T = 1043 K and trapping the pyrolysate in solid argon at T = 10 K. Coarctate fragmentation of the spiroozonide derived from methylenecyclopropane. Photochemically and thermally allowed coarctate fragmentations of spiroketals. Precursors used in this

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• attachment of differing chains on either side of the ketone group by two consecutive intermolecular radical additions to two different alkenes. An application of this property is a simple, yet general route to spiroketals and related derivatives, as shown by the sequence in Scheme 23 [49]. Thus, addition to

• xanthates can be reductively removed by treatment with stoichiometric amounts of peroxide in isopropanol as the solvent, and the resulting product 117 saponified and cyclised with acid into spiroketal 118. By choosing a vinyl or a homoallyl ester as the alkene partner, spiroketals of various ring sizes can

• be easily constructed. Spiroketals 119 and 120 are two such examples. The former was used in the total enantioselective synthesis of (+)-broussonetine G (121) [50]. If one of the alkenes contains a masked aldehyde, a bis-spiroketal such as 122 may be accessed. Furthermore, placing a 1,2- or a 1,3

On the proposed structures and stereocontrolled synthesis of the cephalosporolides

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2012, 8, 1287–1292, doi:10.3762/bjoc.8.146

• strategy for controlling the stereochemistry of oxygenated 5,5-spiroketals. The same strategy likewise enables the first stereocontrolled synthesis of cephalosporolide E, which is typically isolated and prepared admixed with its spiroketal epimer, cephalosporolide F. Keywords: cephalosporolides; chelation

• ; spiroketals; stereocontrol; zinc chloride; Introduction The spiroketal moiety is common in natural products of marine, plant, insect, and bacterial origins [1][2][3][4][5][6][7][8][9][10][11]. The rigidity of the spiroketal provides defined orientation of pendant functional groups, and there is a strong

• correlation between bioactivity and spiroketal stereochemistry in many natural spiroketals. For example, cephalostatin and ritterazine feature thermodynamically disfavored spiroketals that are more cytotoxic than their stereoisomers [12]. Other prominent cytotoxic spiroketals include spongistatin [7] and

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• atoms to form the intermediates 26 or 27, which then rearrange to yield the oxonium intermediates 28 or 29, respectively. Gold(I)-catalyzed intramolecular cyclization of monopropargylic triols 32 has been reported to be a novel and mild approach [29] for producing olefin-containing spiroketals 33 (and

• enantiomer) in excellent yields (Scheme 6). A range of variously substituted triols was prepared which were cyclized to give substituted 5- and 6-membered ring spiroketals. Similarly, the synthesis of the bisbenz-annelated spiroketal core 35 of natural bioactive rubromycins via a gold-catalyzed double

A gold-catalyzed alkyne-diol cycloisomerization for the synthesis of oxygenated 5,5-spiroketals

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2011, 7, 570–577, doi:10.3762/bjoc.7.66

• Sami F. Tlais Gregory B. Dudley Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390 USA, Fax: (850) 644-8281 10.3762/bjoc.7.66 Abstract A highly efficient synthesis of oxygenated 5,5-spiroketals was performed towards the synthesis of the

• ; 5,5-spiroketals; Introduction Spiroketals, exemplified by structure shown in Figure 1, are prominent structural features of many biomedically relevant natural and non-natural target structures [1][2][3][4]. As such, the synthesis of spiroketals has received considerable attention, with most progress

• having been made on systems that include at least one six-membered ring [5]. 5,5-Spiroketals (m, n = 0, Figure 1), particularly oxygenated 5,5-spiroketals such as are found in the cephalosporolides (Figure 2), are the focus of this study. A variety of synthetic methods are available for the synthesis of

A divergent asymmetric approach to aza-spiropyran derivative and (1S,8aR)-1-hydroxyindolizidine

• Jian-Feng Zheng,
• Wen Chen,
• Su-Yu Huang,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2007, 3, No. 41, doi:10.1186/1860-5397-3-41

• Spiroketals and the corresponding aza-spiroketals are the structural features found in a number of bioactive natural products, and in compounds possessing photochromic properties for use in the area of photochemical erasable memory, self-development photography, actinometry, displays, filters, lenses of

• methodology. Background Spiroketals of general structure A (Scheme 1) constitute key structural features of a number of bioactive natural products isolated from insects, microbes, fungi, plants or marine organisms. [1][2][3] The corresponding aza-spiroketal (cf: general structure B) containing natural

• compounds. The observed NOE correlations (in part) and the region expanded NOESY spectrum of compound 7. The skeletons of useful aza-spiroketals and some naturally occurring hydroxylated indolizidines. Synthetic strategy based on N,O-dibenzylmalimide (4). Stereoselectivity synthesis of aza-spiropyran 7