Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• diastereoisomers (2S,4S)-68 and (2S,4R)-68, respectively (Scheme 17) [77][78]. A mixture of (2S,4S)-3 and (2S,4R)-3 obtained after hydrolysis was separated taking advantage of two phenomena: the preferential lactonization of (2S,4S)-3 to produce 69 and much better solubility of (2S,4R)-3 in water when compared

• intramolecular lactonization to form 83 by implementation of the Mitsunobu reaction. After opening of the lactone ring with trichloroethanol and silylation of the hydroxy group oxidation at C5 was performed in the usual way to give a pyroglutamate 84. Benzyl or p-methoxybenzyl esters 85a or 85b were next

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• ). Possibly another ligand exchange between E and KOAc regenerates the Rh complex A (step e). The desired product (35) is obtained after lactonization. Hydrocarboxylation of arylalkenes Hydrocarboxylation is an essential carboxylation reaction. To date, transition-metal-catalyzed hydrocarboxylation reactions

Studies towards the synthesis of hyperireflexolide A

• G. Hari Mangeswara Rao

Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185

• with 2-bromopropene followed by lactonization. Enone 3 could be synthesized from 4 by installation of the methyl group at C-10 followed by cross metathesis reaction. Compound 4 could be obtained from the γ-lactone-fused cyclopentane 5 by deprotection of C-9 followed by allylation at C-8. Previously, we

• of the proposed synthetic sequence. Future studies will include the stereoselective epoxidation of 11 followed by opening of the epoxide and lactonization or 1,4-nucleophilic addition to the α,β-unsaturated ketone 11 followed by epoxidation of the resulted enolate with subsequent lactonization to

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

• intramolecular lactonization of p-substituted phenols 82 to spirooxindoles 83 using 10 mol % of iodobenzene (35) as precatalyst, mCPBA as an external oxidant and TFA as additive. All the catalytic reactions were performed in dichloromethane and spirolactams 83 were isolated in good to excellent yields (Scheme 29

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

• assuming the pathway shown in Scheme 2. The formyl group in aldehyde 2 undergoes nucleophilic trifluoromethylation triggered by a catalytic amount of KF to give the ortho-cyanobenzyl silyl ether 3. Upon treatment with aq HCl, the subsequent lactonization of 4 takes place to afford trifluoromethylphthalide

• considerable importance in chemistry [26][27][28][29][30][31][32]. Enantioselective fluoroalkylation/lactonization reactions are worth investigating since a new stereogenic carbon center next to the fluoroalkyl groups is generated in products 1. To the best of our knowledge, only one successful example of an

•  2, entries 3–5). By employing catalyst 9b, the reaction proceeded at −60 °C to give phthalide 1a in 51% yield with 12% ee (Table 2, entry 4). To improve the enantioselectivity of the present nucleophilic trifluorometylation/lactonization, we surveyed suitable conditions for the catalytic asymmetric

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• led to the displacement of triphenylphosphine. Finally, coumarin derivatives 108 were obtained in yields of 40–90% as a result of intramolecular lactonization of the intermediate fumaric acid derivatives 107 [74]. In an analogous manner, but using 3-aminophenol, 7-aminocoumarin was obtained in a yield

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• β-aminoalcohols. The different nucleophilicity of the NH2 and OH groups determines the sequence of the reaction steps. In the reported cases, the initially formed N-(β-hydroxyalkyl)enamines 79 undergo spontaneous lactonization with the geminal alkoxycarbonyl group leading to the six-membered

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• natural fusaricidin by the Jolliffe group employed a ring closure via a lactonization in solution and subsequent attachment of the side chain to the cyclized depsipeptide [10]. Since the macrolactonization approach suffered from diastereoselectivity issues and low yield, it was decided to perform an on

Sustainable synthesis of 3-substituted phthalides via a catalytic one-pot cascade strategy from 2-formylbenzoic acid with β-keto acids in glycerol

• Lina Jia and
• Fuzhong Han

Beilstein J. Org. Chem. 2017, 13, 1425–1429, doi:10.3762/bjoc.13.139

• -formylbenzoic acid (1a) is attacked preferably by benzoylacetic acid (2a) in the presence of a base to afford the aldol intermediate A. Next, the subsequent facile decarboxylation and lactonization of intermediate A leads to 3-phenacylphthalide (3a). Conclusion In summary, we have accomplished a sustainable and

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• reactions to a C-10 intermediate, i.e., 5-hydroxy-2,4-decenoic acid (72), which undergoes lactonization to yield 29 (Figure 17) [34]. This hypothesis is based on the fact that feeding studies with Trichoderma harzianum and T. viride using [U-14C]linoleic acid or [5-14C]sodium mevalonate revealed the

• ), and of derivatives (by post-PKS reactions) is shown in Figure 18. The authors suggested that seven malonyl-CoA building blocks are connected via Claisen-condensation reactions, followed by aldol-type cyclizations between C-2 and C-7, as well as between C-8 and C-13. The subsequent lactonization yields

• (TE) domain catalyzes the ring-closure and therewith also the off-loading from the PKSI system [79]. A comparable mechanism, in which a TE is involved in off-loading the nascent chain from the PKS assembly line by lactonization, was described for other natural products, e.g., the isochromanone ring

Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins

• Joyeeta Roy,
• Tanushree Mal,
• Supriti Jana and
• Dipakranjan Mal

Beilstein J. Org. Chem. 2016, 12, 531–536, doi:10.3762/bjoc.12.52

• ][25][26][27][28][29][30]. It was then treated with bromine in AcOH to afford 3,5-dibromoorsellinate 20 in 81% yield [31][32][33]. Subsequent O-methylation of 20 (using CH3I, K2CO3), and benzylic bromination of 21 with NBS followed by lactonization of 22 in a refluxing mixture of dioxane and water

Copper-catalyzed intermolecular oxyamination of olefins using carboxylic acids and O-benzoylhydroxylamines

• Brett N. Hemric and
• Qiu Wang

Beilstein J. Org. Chem. 2016, 12, 22–28, doi:10.3762/bjoc.12.4

• ][32][33], as well as an analogous intramolecular electrophilic amino lactonization from our group [34]. Despite these important achievements, current intermolecular olefin oxyamination reactions are often restricted by the use of specific amino and oxygen precursors, limiting the structural diversity

• transformation, integrating an electrophilic amination with a nucleophilic oxygenation, builds upon our recent development in copper-catalyzed olefin difunctionalization, such as copper-catalyzed diamination [40] and amino lactonization [34]. This strategy overcomes common issues of chemo- and regioselectivity

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• lactonization. Although a successful synthetic approach leading to lactone 106 was thus established, further efforts to complete the total synthesis of xeniolide F (12) have yet to be reported. Efforts aimed at constructing the core structure of xenibellol A (15) [15] and umbellacetal (114) [56] employing a 2,3

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• malonyl moiety to the α,β-unsaturated thioester bound to the keto-synthase domain (KS). After this reaction, the polyketide chain is bound to the KS and the acyl carrier protein (ACP). The following lactonization to generate the δ-lactone structure in 4 can either proceed via nucleophilic attack of the δ

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• H2SO4, gallic acid (4) was esterified to methyl gallate (5). The obtained ester 5 was first oxidatively coupled in the presence of o-chloranil, followed by reduction with Na2S2O4 to obtain the hexahydroxy biphenyl 6. Subsequent lactonization afforded the final product, ellagic acid (7), in high yield

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• aldolization followed by a lactonization. This method provides a facile approach to prepare γ-carboxymethyl-γ-lactones and δ-carboxymethyl-δ-lactones under mild reaction conditions. Keywords: aldol addition; cascade reaction; catalysis; conjugate reduction; copper; lactonization; Introduction Paraconic acid

• mainly based on the lactonization of γ-hydroxy esters, which were obtained through either addition of substituted succinate-derived enolates to carbonyls [3][4][5][6][7], or direct reduction of the corresponding γ-keto esters [8]. Usually they were carried out under acidic or basic conditions, which are

• conjugate reduction of the α,β-unsaturated diester with newly generated copper hydride, followed by aldol reaction to yield the key intermediate alkoxide A, which is subjected to further lactonization to form the lactone. Lam’s group has furnished a cobalt-catalyzed conjugate reductive aldolization

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• intermediate 2 undergoes decarboxylation to form 3 through Baeyer–Villiger oxidation to form the 7-membered lactone 4, then hydrolyzation, decarboxylation and lactonization to finally give aspergiloid I (1). Aspergiloid I (1) was evaluated for its cytotoxicity against eleven human cancer cell lines, K562

Total synthesis of the proposed structure of astakolactin

• Takayuki Tonoi,
• Keisuke Mameda,
• Moe Fujishiro,
• Yutaka Yoshinaga and
• Isamu Shiina

Beilstein J. Org. Chem. 2014, 10, 2421–2427, doi:10.3762/bjoc.10.252

• sesterterpene metabolite isolated from the marine sponge Cacospongia scalaris, has been achieved, mainly featuring Johnson–Claisen rearrangement, asymmetric Mukaiyama aldol reaction and MNBA-mediated lactonization. Keywords: aldol reaction; astakolactin; lactonization; MNBA; terpenoids; Introduction

• total synthesis of compound 1 by exploitng the MNBA-mediated lactonization for the formation of its 8-membered lactone moiety. Results and Discussion The rationalized synthesis of 1 primarily involved the linear synthesis of the prenyl chain precursor from commercially available (E,E)-farnesol to form

• the corresponding seco-acid and the subsequent construction of the 8-membered lactone moiety. The retrosynthetic analysis of 1 is depicted in Scheme 1 [31]. First, the 8-membered ring in 1 could be efficiently constructed via lactonization using MNBA with DMAP. The chain precursor 2 would be

End group functionalization of poly(ethylene glycol) with phenolphthalein: towards star-shaped polymers based on supramolecular interactions

• Carolin Fleischmann,
• Hendrik Wöhlk and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 2263–2269, doi:10.3762/bjoc.10.235

• broad variety of applications [36][37][38][39]. An adequate guest molecule for β-CD is the well-known indicator dye phenolphthalein [40]. In addition to its relatively high affinity to β-CD, this molecule undergoes a decolorization in basic solution as the complexation induces a re-lactonization of the

• (see Figure 1), which were subjected to further investigations. Investigation of the complex formation behavior Due to the fact that in basic solution the complexation of PP by β-CD is accompanied with a decolorization due to the re-lactonization of the molecule, a first evaluation of the complex

A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

• J. Alexander Willms,
• Rita Beel,
• Martin L. Schmidt,
• Christian Mundt and
• Marianne Engeser

Beilstein J. Org. Chem. 2014, 10, 2027–2037, doi:10.3762/bjoc.10.211

• enamine structure II. On the other hand, the comparison with the fragmentation of the structurally related ion [II*b]+ (Figure 5b) is instructive. It doubtlessly possesses an enamine structure since it can neither form a zwitterionic iminium ion nor undergo lactonization to oxazolidinone II’’b because of

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• conjugate addition of methanol and lactonization. The second cyclic building block, syn-dihydropyran 188, could be synthesized by a highly diastereoselective 6-endo-trig cyclization of an allylic 1,3-diol, which was developed by Hanessian and co-workers [141]. The required allylic 1,3-diol would also be

Homogeneous and heterogeneous photoredox-catalyzed hydroxymethylation of ketones and keto esters: catalyst screening, chemoselectivity and dilution effects

• Axel G. Griesbeck and
• Melissa Reckenthäler

Beilstein J. Org. Chem. 2014, 10, 1143–1150, doi:10.3762/bjoc.10.114

• acetophenone/methanol reaction: types I–III. Photohydroxymethylation and subsequent lactonization of keto esters. Model reaction for heterogeneous and dye-sensitized catalysis. Product forming routes I to III for photoredox catalysis of methanol/carbonyl compounds. Photoredox initiated steps on semiconductor

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• -benzyloxyhex-5-enal [30], oxidative degradation of aromatics and subsequent lactonization [31], and a two-carbon homologation of an enantiopure C4-building block with a metallated sulfone [32]. A combinatorial biosynthetic approach to D- and L-amicetose has also recently been established by combining different

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Decandrinin, an unprecedented C₉-spiro-fused 7,8-seco-ent-abietane from the Godavari mangrove Ceriops decandra

• Hui Wang,
• Min-Yi Li,
• Félix Zongwe Katele,
• Tirumani Satyanandamurty,
• Jun Wu and
• Gerhard Bringmann

Beilstein J. Org. Chem. 2014, 10, 276–281, doi:10.3762/bjoc.10.23

• double bond of int B could yield int C. Finally, the lactonization of int C would give decandrinin (1) (Scheme 1). Experimental General methods Optical rotation values were recorded on a JASCO P-1020 polarimeter. CD spectra were recorded on a J-715 spectropolarimeter (JASCO, Gross-Umstadt, Germany). UV