Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• centres is claimed (C-17 and C-3’). However, no indication was provided regarding their stereochemistry, yet only one stereoisomer was isolated in a pure form. Spiro steroids with five-membered heterocycles 17-Spirolactone steroids In 2000, Poirier’s group reported an efficient synthesis of a spiro-γ

• -lactone motif on an estradiol backbone [17]. Beginning with the 7α-alkanamidoestrone derivative 17, a nucleophilic addition by the anion of the THP propargyl ether occurred stereoselectively and provided the alkyne 18 in a 75% yield. Afterwards, the catalytic hydrogenation of the alkyne with a 1:1 mixture

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• -unsaturated γ-lactone ring. The HMBC cross-peaks (Figure 2) from H-11 (δH 5.86) to C-10, C-12, and C-13, and from H-15 (δH 6.03) to C-12, C-13 and C-14 allowed the location of an extended conjugated π-system at C-11 and C-12. Moreover, the downfield shift of C-14 (δC 72.2) and the HMBC correlation between H3

• ′-acetoxypterolobirin B (3) together with one known analogue were isolated from the MeOH extract of P. macropterum fruits. Their structures and absolute configurations of 1 and 3 were established by spectroscopic analyses and ECD data. Compound 1 has an extended conjugated π-system with an α,β-unsaturated γ-lactone

• colorless oil. The molecular formula was assigned to be C44H60O9 based on the HRESI–TOF–MS analysis with a [M + H]+ ion peak at m/z 733.4305 (calcd for C44H61O9, 733.4310) and NMR data, implying 15 degrees of unsaturation. The IR absorption band at 1724 cm−1 suggested the presence of α,β-unsaturated γ

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• equivalents of water interrupted the cyclization step and led entirely to reductively coupled alkenylated ring-opened products. Interestingly, when this methodology was applied to the ester-bearing oxabicyclic 1a, the anticipated reductive coupling product was not detected; instead, bicyclic γ-lactone 4 was

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• Astericus aquaticus (Asteraceae) which possesses a unique backbone featuring a cyclobutane moiety fused to a cyclopentane ring, a γ-lactone, and an eight-membered enone [60][61]. Zhang and Gu achieved its preparation through the use of a late-stage intramolecular NHK reaction (Scheme 23) [62]. Thus, when

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

• species to the α-ketoester 15 (Scheme 3) [6]. The ketoester 15 was synthesized by a chiral pool approach starting from (+)-3-carene derived cycloheptenone 13 [7][8] and aldehyde 12 (accessible from (R)-Roche ester [9]) via the γ-lactone 14. The ketoester moiety was established by an enolate hydroxylation

• reactivity in their synthesis of (+)-awajanomycin (92), a marine natural product with a γ-lactone-δ-lactam core structure (Scheme 15) [30][31]. Key step was an asymmetric allylboration of diethyl mesoxalate (90a) with boronate 89, which was easily accessible through a Matteson homologation of dichloromethyl

Sesquiterpenes from the soil-derived fungus Trichoderma citrinoviride PSU-SPSF346

• Wiriya Yaosanit,
• Vatcharin Rukachaisirikul,
• Souwalak Phongpaichit,
• Sita Preedanon and
• Jariya Sakayaroj

Beilstein J. Org. Chem. 2022, 18, 479–485, doi:10.3762/bjoc.18.50

• , Nakhonsithammarat 80160, Thailand 10.3762/bjoc.18.50 Abstract Two new sesquiterpenes, trichocitrinovirenes A (1) and B (2), and five known compounds including four structurally related sesquiterpenes and one γ-lactone were isolated from the soil-derived fungus Trichoderma citrinoviride PSU-SPSF346. The structures

• . Compound 2 possesses a rare bicyclic sesquiterpene skeleton. The antimicrobial and cytotoxic activities of the isolated compounds were evaluated. Keywords: antimicrobial activity; cytotoxic activity; γ-lactone; soil-derived fungus; sesquiterpene; Trichoderma citrinoviride; Introduction The fungus

• chromatography techniques led to the isolation of two new sesquiterpenes, trichocitrinovirenes A (1) and B (2), four known structurally related sesquiterpenes including gliocladic acid (3), hydroheptelidic acid (4), and xylaric acids B (5) and D (6) [8], as well as one known γ-lactone, fusidilactone A (7) [9

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• contained ithomiolide A (3), a pyrrolizidine alkaloid derived γ-lactone, I. s. derasa carried the sesquiterpene α-elemol (8) in the androconia. These differences might be important for the reproductive isolation of the two subspecies, in line with previously reported low gene exchange between the two

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• , where the β-hydroxymethyl-γ-lactone 14 was obtained, confirmed an electronic influence of the fluorine atom on these ring-opening reactions (Table 3, entries 1 and 2). In the case of fluoroalkylidene-oxetane 12 and, in contrast with 16, when subjected to HBr/AcOH, the electronic repulsion induced

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• reduction with NaBH4 to give the primary alcohol 19. In contrast to benzaldehyde 7, carbaldehyde 18 showed no decomposition at ambient temperature. While acidic hydrolysis of 19 provided exocyclic γ-lactone 20, the substitution reaction with DPPA/NaN3 yielded the primary azide in 87% yield. In accordance to

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

• decomposition of this stereoisomer including racemization at Cα. From pentose via 2,3-aziridino-γ-lactone In the so called “2,3-aziridino-γ-lactone methodology” [18][99][100] ribose (or lyxose) is used as a starting material [101][102] which is transformed into the lactone 95 in several steps [99]. Boron

• protected 3,4-dihydroxy-L-glutamic acid 96 and the respective γ-lactone 97 formed from 96 in the presence of acids. Benzyl alcohol was selected to refrain from decomposition of the final amino acids during the acid hydrolysis of, e.g., methyl esters [99] since for a mixture of 96 and 97 hydrogenolysis

Ring-opening metathesis of some strained bicyclic systems; stereocontrolled access to diolefinated saturated heterocycles with multiple stereogenic centers

• Zsanett Benke,
• Melinda Nonn,
• Márton Kardos,
• Santos Fustero and
• Loránd Kiss

Beilstein J. Org. Chem. 2018, 14, 2698–2707, doi:10.3762/bjoc.14.247

• functionalized derivatives such as bicyclic lactones, γ-lactams or isoxazolines, derived from various cyclodienes and to evaluate their chemical behavior under Ru-catalyzed ring-opening conditions (Scheme 2). First, the ring opening of racemic bicyclic γ-lactone (±)-3 (derived from cyclodiene 1 via β-lactam

• catalysts, bicyclic lactone (±)-4 a stereoisomer of (±)-3 furnished olefinated γ-lactone (±)-6 similar to (±)-5 (Scheme 3, Table 2). Unfortunately, ROM reactions, however, took place with total conversions, they were always accompanied by the formation of a significant amount of polymeric materials (ROMP

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

• G. Hari Mangeswara Rao Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur-208016, India Department of Chemistry, Texila American University, Georgetown, Guyana 10.3762/bjoc.14.185 Abstract The first approach to hyperireflexolide A, based on the synthesis of γ-lactone-fused

• antifungal [2] and cytotoxic activities [3]. γ-Lactone-fused cyclopentanes are of vital importance in organic synthesis and are the most abundant substructures found in various naturally occurring molecules [4][5]. A cis-cyclopentane ring-fused γ-lactone is the key structural unit of many complex and

• challenging biologically active natural products [6][7][8][9][10][11][12][13][14][15][16][17][18][19]. The γ-lactone-fused cyclopentane ring system is also an important component for the synthesis of a variety of cyclopentanoid natural and unnatural products [20][21][22][23][24]. In the literature, numerous

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• described in Scheme 3, Jeong et al. chose a 2,3-di-O-isopropylidene-protected intermediate as a donor of glycosylation, which was synthesized based on their method developed for 4’-thionucleosides. Starting from compound 64, which was obtained from D-gulonic γ-lactone, dimesylate 66 was prepared. The

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

• José Enrique Barquera-Lozada and
• Gabriel Cuevas

Beilstein J. Org. Chem. 2017, 13, 1969–1976, doi:10.3762/bjoc.13.192

• considered when a prediction of the configuration of an elemane is determined before a Cope rearrangement. Finally, we studied the role the γ-lactone ring plays in the transformation of germacranes into elemanes. Takeda et al. carried out a series of experiments, which proved that γ-lactone rings prevent the

• versus that of a germacrane determines the likelihood of the transformation. The conclusion is that the γ-lactone ring in the Cope rearrangement destabilizes the corresponding elemane and it has a little or no effect in the Cope TS. This conclusion could be extrapolated to any 5-membered or smaller rings

• . The smaller a ring is the more susceptible it is to the strain generated by a second ring (5-members or smaller) fused to it. Therefore, the impact of the γ-lactone ring on the elemane ring (6-members) is significantly more than on the Cope TS ring (10-members). Conclusion The Cope rearrangement is

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• system bearing a γ-lactone terminus constitutes the right half of the molecule. To date, no structurally related natural products are known except for its demethyl congener butyrolactol B that was also isolated from the same strain and has an isopropyl group instead of the tert-butyl terminus [9]. Very

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• for the oxidative production of valuable intermediates [264][265][266][267][268][269]. The asymmetric oxidation of 3-substituted cyclopentane-1,2-diones 87a–f is an efficient tool in organic synthesis for the preparation of unsymmetrical γ-lactone acids 88a–f with high optical purity and good yields

• (Table 6). These γ-lactone acids are valuable substrates for the synthesis of compounds with potentially useful pharmacological properties, such as homocitrates, alkyl- and aryl-substituted nucleosides [270][271][272]. The reaction starts with an asymmetric epoxidation of the substituted cyclopentane-1,2

• -dione 87a to form epoxide 89a. The second step involves the Baeyer–Villiger oxidation of epoxide 89a to peroxide 90a followed by the rearrangement into intermediate 91a. The latter is hydrolyzed by H2O to form dicarboxylic acid 92a, which is cyclized under the acidic conditions to γ-lactone acid 88a

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• configurational assignment is ambiguous in this case, the NMR data and the fact that no γ-lactone is formed strongly support the trans-arrangement of the two functional groups as depicted. Under similar conditions (5 mol % Pd(PPh3)4, 90 °C, 3 d) the isopropyl-substituted ketone 2 furnished a mixture of the

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• of the molecule. However, the complete natural product has not yet been synthesized [61]. The enhygrolide group of compounds comprises enhygrolide A (27) and B (28). These molecules resemble cyanobacteria-derived metabolites, known as nostoclides and cyanobacterin, which also have a γ-lactone-moiety

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• much more slowly than cyclopentanone derivative 3a (Table 3, entries 5, 6, and 8), although the reaction time could be reduced from 96 h to 10 h in the reaction of 1a with 3b by increasing the catalyst loading from 2 mol % to 5 mol % (Table 3, entry 7). It is also noteworthy that 2-acetyl-γ-lactone (3e

• diastereoselectivity for the reaction of 1a with 2g (dr 74:26), but the yields for the reactions with 2-substituted malonates (2b–d) were only moderate (entries 9–11 in Table 2). Next, we extend the study to the reaction of different β-functionalized cycloalkanones (3a–c), 2-acetylcyclopentanone (3d), and 2-acetyl-γ

• -lactone (3e) with nitrostyrene derivatives 1a–d (Scheme 3 and Table 3). The electronic nature of the nitroolefins only affects the yield and the reaction time, being longer as the donating effect of the substituent increases, but maintaining good diastereoselectivity and excellent enantioselectivity for

New synthetic strategies for xanthene-dye-appended cyclodextrins

• Milo Malanga,
• Andras Darcsi,
• Mihaly Balint,
• Gabor Benkovics,
• Tamas Sohajda and
• Szabolcs Beni

Beilstein J. Org. Chem. 2016, 12, 537–548, doi:10.3762/bjoc.12.53

• -B lactone belongs to the carbonyl stretching of the γ-lactone moiety of the dye and this value is very similar to that found in the carbonyl region of the IR spectrum of Rho-β-CD at 1755.4 cm−1. This last frequency is typical for the carbonyl stretching of a γ-lactam ring [27], thus demonstrating

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

• . Addition of lithium acetylide 41 to the keto group led to acetal 42. Hydrogenation of the triple bond under basic conditions resulted in cleavage of the acetal and ring closure to the corresponding lactol which was oxidized with chromic acid to furnish γ-lactone 43. An ensuing Dieckmann condensation [32

• as the dimethoxy acetal and reduction of the lactone followed by olefination furnished alkene 143. The lactone fragment of the natural product was then installed by acidic hydrolysis of the acetal functionality and subsequent oxidation gave γ-lactone 144. Ozonolysis of the terminal alkene and

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

• and its analogues, sharing the similar structure of a γ-lactone with an attached β-carboxylic acid, are widely found in natural products. Related syntheses have been actively explored due to the potential antitumor and antibiotic activities of these compounds [1][2][3][4]. The synthesis methods were

• [15], respectively. Although syntheses of β-carboxy-γ-lactones have been studied extensively, synthetic methods for γ-carboxymethyl-γ-lactones have been scantly explored. Taking into account the known bioactivities of the β-carboxy-γ-lactone class, its close isomer γ-carboxymethyl-γ-lactone should be

• of pharmaceutical interest as well. To date we have found only one example of the synthesis of the γ-carboxymethyl-γ-lactone involving the reaction of α-bromocarboxylate with zinc and a γ-oxocarboxylate [16]. To this end, we are attempting to explore its preparation and herein reporting the synthesis

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

• three-step procedure and subsequent alkylation with allyl bromide gave alkene 87. Ozonolysis with reductive work-up was followed by spontaneous cyclization to the corresponding γ-lactone, which was then transformed into 83 by means of α-selenenylation, oxidation, and elimination (Scheme 11). With

• ozonolysis, protection of the resulting aldehyde, reduction of the lactone ring to the lactol, and treatment with methylenetriphenylphosphorane delivered 89. Mild acidic hydrolysis of the acetal followed by oxidation then yielded 90 with the γ-lactone unit that constitutes ring A of acetoxycrenulide

Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of ¹³C chemical shifts

• Simone Di Micco,
• Angela Zampella,
• Maria Valeria D’Auria,
• Carmen Festa,
• Simona De Marino,
• Raffaele Riccio,
• Craig P. Butts and
• Giuseppe Bifulco

Beilstein J. Org. Chem. 2013, 9, 2940–2949, doi:10.3762/bjoc.9.331

• , 1 and 2 share with other members of this family a large portion of their chemical scaffold including the γ-lactone moiety and the ethyl-branched side chain. Even if the absolute configuration at C-4 and C-6 has been previously determined for plakilactone A (4) and notably for the corresponding 7,8

• molecular formula of C16H26O3 as deduced by HRMS–ESI analysis. The proton and carbon signals of the 2,4-diethyl γ-lactone were almost identical to those of the corresponding part of plakilactone G (1), whereas differences were observed in the C-8 side chain. Two mutually coupled signals at δH 2.50 (dd, J