Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• combretastatin D-1 (1) in 23% overall yield after 16 steps. Later, the same authors performed the enantioselective synthesis of 1 in an attempt to review its absolute configuration [41]. Thus, acetylation of compound 2 followed by the use of Jacobsen’s catalyst [42] to perform the epoxidation of the double bond

• synthesis of combretastatin D-2 (2) by Rychnovsky and Hwang [36]. Divergent synthesis of (±)-1 form combretastatin D-2 (2) by Rychnovsky and Hwang [36]. Enantioselective synthesis of 1 by Rychnovsky and Hwang employing Jacobsen catalyst [41]. Synthesis of fragment 57 by Couladouros and co-workers [43][45

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• [112][113][114][115][116], no enantioselective synthesis is available. Full 1H and 13C NMR data of 53 (including 14 carbon signals) have been published [113]. The guaiane sesquiterpenes that are potentially derived from cationic intermediates L1–L4 are summarised in Scheme 16A. trans-β-Guaiene (54) can

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• chromatography; enantioselective synthesis; GC/MS; semiochemicals; Introduction Hyperolius cinnamomeoventris (Figure 1) is one of the largest species of reed frogs (Hyperoliidae), which are commonly found in Africa, south of the Sahara. Males of the Hyperoliidae possess a characteristic yellow gular patch on

• ) rt, 45 min; e) IBX (3.0 equiv), EtOAc, reflux, 3 h; f) i) CH2=CHMgBr (1.5 equiv) Et2O, 0 °C, ii) rt, 20 min; g) IBX (3.0 equiv), EtOAc, reflux, 6 h; h) i) MeMgBr (1.5 equiv) Et2O, 0 °C, ii) rt, 30 min; j) NaOMe (25.0 equiv), MeOH, rt, 60 h. Enantioselective synthesis with (S)-Jørgensen’s

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• chain to the 2,5-cyclohexadienone scaffold. Avoiding heat and light sensitive tetraenes, the convergent plan would also give the opportunity to assess an enantioselective synthesis of the targets, noting that the C14 epimeric product, isotridachiapyrone B, has also been isolated by Schmitz. Results and

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• to be tackled. A highly enantioselective synthesis is still desirable, as the only synthesis offering >90% ee relies on the combination of chiral ligands and chiral auxiliary. Moreover, to date only 6 natural products from the grayanane family were synthesized, out of the more than 160 compounds

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• chemistry; levoglucosenone; oxa-Michael reaction; Introduction (−)-Levoglucosenone (1) is formed from the acid-catalyzed pyrolysis of cellulose along with minor amounts of furfural and 5-methylfurfural [1][2][3]. It has emerged as a promising starting material for enantioselective synthesis from materials

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• enantioselective synthesis in modern chemistry turns out to be accumulatively essential for the preparation of chiral drugs, which is a huge growing market in the future. Indeed, the asymmetric ring opening of terminal epoxides is one of the most important strategies for synthesizing drug-like building blocks and

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• preparation and the coupling of three main fragments (Figure 2): the lactone fragment 3, the central fragment 4 and the cyclohexane fragment 5. We have previously described the enantioselective synthesis of the lactone fragment 3 [18]; we now disclose the synthesis of the oxazinone 4 and attempts for coupling

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• isolated. Moreover, the coupling of benzothiazines with amino acids was realized. In doing so, an enantioselective synthesis of the nonproteinogenic amino acid 2-amino-3-propylhexanoic acid was accomplished. Keywords: amino acid; benzothiazine; oxidative dimerization; peptide coupling; stereoselective

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• hangtaimycin, TDD and the hangtaimycin degradation product HTM222 are given. Keywords: antibiotics; enantioselective synthesis; peptides; racemisation; Streptomyces; Introduction Hangtaimycin (1, Scheme 1) was first isolated from Streptomyces spectabilis and shown to possess weak antimicrobial activity

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

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

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• furnished a chiral thiosquaramide-catalyzed tandem Michael–Henry reaction of phenacylmalononitriles and nitroolefins for the enantioselective synthesis of cyclopent-3-ene-1-carboxamides [32] (reaction 2 in Scheme 1). Mohanan and co-workers reported a PBu3-catalyzed [3 + 2] annulation of

The stereochemical course of 2-methylisoborneol biosynthesis

• Binbin Gu,
• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82

• 2-methylisoborneol from (S)-2-Me-LPP may be explained by isomerization to 2-Me-GPP and then to (R)-2-Me-LPP. Keywords: biosynthesis; enantioselective synthesis; enzyme mechanisms; gas chromatography; terpenoids; Introduction After its first discovery from Streptomyces [1][2], it has been

• )-2-Me-LPP is the true pathway intermediate towards compound 1. For this purpose, both enantiomers of 2-Me-LPP were synthesized and enzymatically converted by 2MIBS. Here we report on the enantioselective synthesis of (R)- and (S)-2-Me-LPP and the results from the incubation experiments with 2MIBS

• . Results and Discussion Enantioselective synthesis of 2-methyllinalyl diphosphate The synthesis of (R)- and (S)-2-Me-LPP started with the Horner–Wadsworth–Emmons reaction [34][35] of sulcatone (2) with triethyl 2-phosphonopropionate to obtain ethyl 2-methylgeranate (3) as a mixture of the E and Z

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• anomeric hydroperoxides (HPO) to obtain epoxides 40 with moderate ees (Scheme 11B) [100][101]. Bunge and co-workers used the enantiomerically pure dihydroperoxide 41 in the DBU-mediated epoxidation of menadione (10) for the enantioselective synthesis of epoxide 42 (92% yield and 45–66% ee) (Scheme 11C

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• or new methodologies to construct the spirobarbiturates with diverse structures. In recent years, good progress has been achieved in the construction of racemates of spirobarbiturates and the enantioselective synthesis [24][25][26][27][28][29], but only limited progress has been made in the

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• phosphoric acid-catalyzed synthesis of axially chiral compounds and to suggest that much more attention should be paid to these catalysts in order to promote asymmetric synthesis. Review 1. Enantioselective synthesis of atropisomeric biaryls Direct C–H functionalization strategies for the atroposelective

• (Brønsted acidity/basicity, hydrogen-bonding units, and counter-anions toward metals) [48][49]. In 2019, Shi, Lin, and co-workers achieved an enantioselective synthesis of axially chiral quinoline-derived biaryl atropisomers via Pd-catalyzed C–H olefination of 8-phenylquinoline (11) using a novel chiral

• bioactive molecules and chiral catalysts [62][63][64], the construction of this scaffold has recently become valuable and attracted the attention of chemists [2][64]. In this context, Shi and co-workers reported a new strategy for the enantioselective synthesis of axially chiral naphthylindoles via the

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

• directly with the presilylated cytosine without any promoter or additive and gave nucleoside 93 in a selective manner (β/α 10:1). The ester group of nucleoside derivative 93 was further reduced with sodium borohydride in ethanol, which gave lamivudine (1). An efficient and enantioselective synthesis of

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• the asymmetric aza-Michael addition reactions. Mahe et al. reported an effective, eco-friendly and cost-effective enantioselective synthesis of 3,5-diarylpyrazolines 49 by using phase-transfer methodology. They carried out a set of reactions between chalcones 46 and N-tert-butoxycarbonylhydrazine (47

• yields ranged 57–89% with ee 70–97% [52]. A similar chiral multifunctional thiourea/boronic acid was used as an organocatalyst by Michigami et al. for the enantioselective synthesis of N-hydroxyaspartic acid derivatives 76 with perfect regioselectivity and high enantioselectivity (Table 17) [53

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• annulation. Recently, there have been several elegant reviews covering the 1,3-enynes chemistry [46][47][48]. For instance, Procter and co-workers reviewed the copper-catalyzed functionalization of enynes [46]. In 2020, the Wang group reviewed the development of 2-activated 1,3-enyne in enantioselective

• synthesis [47]. Further, the Liu group reviewed the synthesis of allenes via transition metal-catalyzed 1,4-functionalizations of unactivated 1,3-enynes [48]. In this review, we will highlight the recent advances in the tandem annulation reactions of 1,3-enyne structural motifs for the construction of

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• is the binaphthol (BINOL)-derived phosphoric acid class of catalysts, firstly reported by Akiyama [25] and Terada [26]. Soon after, BINOL-derived phosphoric acids were employed in the enantioselective synthesis of 2,3-dihydroquinazolinones. The initial report in this area was made by List and co

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• report we disclose the outcome of an investigation into the design of an efficient catalytic asymmetric system capable of manipulating this substrate and its application to the enantioselective synthesis of the potent CRTH2 receptor antagonist 6 [32] (Scheme 1C). Results and Discussion We began our

• through the enantioselective synthesis of the (S)-antipode potent CRTH2 receptor antagonist 6 [48] (Scheme 2). Compound 10Al, isolated in 76% ee, was recrystallised in n-hexane to obtain optically pure 10Al. This material was deprotected with benzylamine 11 to afford oxindole 12, which was subsequently N

• brackets refers to reaction conducted at 3 °C, using 10 mol % of catalyst. dPerformed in PhCH3. ePerformed using 7c as the catalyst. A) SN2 alkylation of 3-subtituted-2-oxindoles not readily functionalisable; B) Previous work: enantioselective synthesis of a malleable 2-oxindole capable of further

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• have been provided by the group of Jacobsen in the nucleophilic addition of indoles 17 to pyranones 62 (Scheme 14a) [71], as well as in the enantioselective synthesis of α-allyl amino esters 67 by the reaction of α-chloro amino acid derivatives 65 with allyltin and allylsilane 66 nucleophiles [72

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• Zara M. Seibel Jeffrey S. Bandar Tristan H. Lambert Department of Chemistry, Columbia University, New York, New York 10027, USA Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA 10.3762/bjoc.17.134 Abstract A procedure for the enantioselective synthesis

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

• a specific target, i.e., it gives access to a greater diversity of compounds to be explored [26]. In this work, a compilation of the enantioselective synthesis of coumarin derivatives using asymmetric organocatalysis is presented, highlighting the proposed mechanism pathways for the formation of the

• substitution reaction between the coumarin and the activated MBH substrate, it is possible to obtain functionalized coumarins 41 (Scheme 13). Furthermore, the absolute configuration of the stereogenic center was determined by X-ray crystallography. The enantioselective synthesis of cyclopropa[c]coumarins 45

• -hydroxycoumarin (1) with the chiral catalyst 48, as shown in Scheme 15 [48]. The enantioselective synthesis of dihydrocoumarins 51 from an inverse demand [4 + 2] cycloaddition of ketenes 50 with o-quinone methides 49 using carbene catalyst (NHC) 52 was described by Ye and co-workers [49].This transformation

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

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

• literature, several strategies are reported using the sulfinyl group [84][85][86][87][88]. In this context, an enantioselective synthesis of 4-substituted azetidin-2-ones 52 was also accomplished starting from chiral imines 14 and dimethyl malonate (49). A diastereoselective coupling of these components

• ) [105]. Li and Xu reported a method for the enantioselective synthesis of β,γ-unsaturated α-amino acids 100, by a Lewis acid-promoted diastereoselective Petasis reaction of vinylboronic acids 98, (R)-N-tert-butanesulfinamide and glyoxylic acid (99). They found that the best results were obtained working

• high yields of 95% and 94%, respectively [132] (Scheme 42). Pinto and co-workers reported recently the enantioselective synthesis of natural alkaloids (−)-cermizine B 171 and (+)-serratezomine E 172. A key step of the synthetic strategy is the allylation with allylmagnesium bromide of N-tert