Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• of linkers are unsuitable, as they rendered the peptide inactive (results not shown). However, disulfide-bonded linkers retained activity, presumably by cleavage in the reductive milieu of cancer cells, if connected via a short ester or amide linkage at the C-terminus. The retrosynthetic analysis

• ). Retrosynthetic analysis of the modular attachment linker tubugi-1-SSPy (3). Synthesis of tubugi-1-SSPy (3): a) LiOH·H2O, THF/H2O, 0 °C → rt; b) Ac2O, py; c) 4, HBTU, DMF, DIPEA, MeOH, under N2 atmosphere, 42% (3 steps). Synthesis of the tubugi-1–NPY conjugate [K4(C(tubugi-1)-βA-),F7,L17,P34]-hNPY (8). Toxin

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• functionalized side chains are introduced prior to coupling and ring closure to afford 8. This new synthetic route would be more convergent and efficient for the preparation of 3. Retrosynthetic analysis led to 9 and 10 as two key synthons, which would be assembled via a Mitsunobu–Fukuyama reaction, and

Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I

• Pamarthi Gangadhar,
• Sayini Ramakrishna,
• Ponneri Venkateswarlu and
• Pabbaraja Srihari

Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206

• strongylodiol I The retrosynthetic analysis for strongylodiols H and I is delineated in Scheme 1. We envisaged that the target molecules strongylodiol H (9) and strongylodiol I (10) can be synthesized by a Wittig reaction of a common intermediate aldehyde 14 with triphenylphosphonium Wittig salts 15 and 16

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

• 5 could not only act as a surrogate for C-9 carbonyl but also facilitate installation of an angular methyl group. The retrosynthetic analysis for hyperireflexolide A is depicted in Scheme 1. We envisioned that hyperireflexolide A (1) could be synthesized by metal-catalyzed opening of the epoxide 2

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• sequential glycosylation strategies. Results and Discussion Keeping in mind our objective to synthesize the SPn 6A tetrasaccharide following stepwise as well as one-pot synthetic strategies based on common building blocks, a retrosynthetic analysis was made which led us to galactose-based donor 2 [26

• linkages could be prepared with a yield and a selectivity which were high enough to allow the one-pot synthesis. The tetrasaccharides associated with the pneumonicoccal serogroup 6. Retrosynthetic analysis. Preparation of D-glucosyl donor 6. Reaction conditions: a) NapBr/PMBCl, NaH, DMF, rt, 12 h, 90% (6a

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• examples. X-ray crystal structure of hydantoin-fused triazolobenzodiazepine 10a. (Displacement ellipsoids are drawn at the 30% probability level.) Retrosynthetic analysis towards 2,5-diketopiperazine fused triazolobenzodiazepine. Ugi 4-CR reaction. Synthesis of diketopiperazine-fused triazolobenzodiazepine

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• efficient stereocontrol. To the best of our knowledge such approach involving a double auxiliary and catalyst stereocontrol was never applied before to asymmetric synthesis of enantioenriched isoindolinones. Results and Discussion Retrosynthetic analysis From a retrosynthetic point of view, (3S)-NH free 3

• active chiral 3-substituted isoindolinones. Esters 12a–e, 13 prepared, isolated yield. Benzamides 6a–d, 7a–e, 8 prepared, isolated yield. Phase transfer catalysts (PTC) used in this study. ORTEP plot of isoindolinone (2R,3S)-3a (CCDC 1590565) [68]. Retrosynthetic analysis of NH free chiral 3-substituted

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• ]. With these issues in mind, we carried out a retrosynthetic analysis (Scheme 2) in which 10, an iodo analogue to the starting material 3, could be generated in a single step via a decarboxylative ring-opening of α-acetyl butyrolactone 8. The iodo analogue 10 could then be used without isolation to

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• retrosynthetic analysis is depicted in Scheme 1. The initial step comprises the photodecarboxylative addition of phenylacetate to commercially available N-(bromoalkyl)phthalimides, yielding the corresponding benzylated hydroxyphthalimidine derivatives as key intermediates. Subsequent acid-catalyzed dehydration

• ]. Molecular structures of AL-12, AL-12B and AL-5. Crystal structures of photoaddition products 3a (left) and 3b (right). Crystal structure of (E)-7a. Side view and front view. Crystal structure of (Z)-8a. Side view and front view. Retrosynthetic analysis of AL-12, AL-12B and AL-5 (in their neutral forms) and

A semisynthesis of 3'-O-ethyl-5,6-dihydrospinosyn J based on the spinosyn A aglycone

• Kai Zhang,
• Shenglan Liu,
• Anjun Liu,
• Hongxin Chai,
• Jiarong Li and
• Lamusi A

Beilstein J. Org. Chem. 2017, 13, 2603–2609, doi:10.3762/bjoc.13.257

• to synthesize other rhamnose analogues. The structures of spinosad and spinetoram. Chemical modifications of spinosyn J and spinosyn L. Retrosynthetic analysis of 3'-O-ethyl-5,6-dihydrospinosyn J. Hydrolysis of spinosyn A and formation of the aglycone and D-forosamine. Synthesis of 3-O-ethyl-2,4-di-O

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• only to symmetrical products and can be detrimental for more fragile molecules such as substituted enantiomerically pure compounds. As shown by a retrosynthetic analysis (Scheme 1), a classical milder approach would consist in preparing first the dipeptide, followed by an intramolecular ester

Synthesis of substituted Z-styrenes by Hiyama-type coupling of oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane

• James R. Vyvyan,
• Courtney A. Engles,
• Scott L. Bray,
• Erik D. Wold,
• Christopher L. Porter and
• Mikhail O. Konev

Beilstein J. Org. Chem. 2017, 13, 2122–2127, doi:10.3762/bjoc.13.209

• established in applying the Buchwald–Hartwig coupling to 15, producing the benzoxocane 24, which contains the carbon skeleton of heliannuol A. Retrosynthetic analysis of heliannuol A. Hydrosilylation of alkynols. Hydrogenation of benzoxocane 24. Pd-catalyzed couplings of oxasilacycloalkenes with aryl iodides

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• acid synthesis. With continuous development, the preactivation strategy will achieve wider applications in complex carbohydrate synthesis. Representative structures of products formed by the preactivation-based dehydrative glycosylation of glycosyl hemiacetal. Retrosynthetic analysis of pentasaccharide

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

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• been described again by the Menche group following a sequence that was related to their archazolid A synthesis. Menche’s retrosynthetic analysis and strategy As a prelude to initiating a synthetic campaign directed towards the archazolids the Menche group first elucidated the full stereochemistry and

• synthesis was enabled by the group of Trauner and will be discussed below. Trauner’s retrosynthetic analysis and strategy Shortly after the total synthesis of archazolid A (1) by Menche et al. [41] the total synthesis of archazolid B 2 was reported by Trauner and co-workers [43]. As shown in Scheme 8, they

• to synthesize archazolid B (2) in only 19 steps from (S)-Roche ester 41 (longest linear sequence). O'Neil’s retrosynthetic analysis and strategy As discussed above one of the main difficulties of any archazolid synthesis involves the labile C1 to C5-dienoate system, which is prone to isomerization

First total synthesis of kipukasin A

• Chuang Li,
• Haixin Ding,
• Zhizhong Ruan,
• Yirong Zhou and
• Qiang Xiao

Beilstein J. Org. Chem. 2017, 13, 855–862, doi:10.3762/bjoc.13.86

• ’-transesterification is inevitable to occur in nucleosides [19][20][21]. The synthetic route would be lengthy and cumbersome. Therefore, a practical total synthesis is in high demand to facilitate the preparation of other kipukasins and their analogues. The retrosynthetic analysis is shown in Figure 2 (path b

• ) complexes with high yield and selectivity. The conditions are very mild and neutral. In the present paper, we continue to use ortho-alkynylbenzoate as protecting group for the 5’-OH group to fulfill the total synthesis of kipukasin A. According to the retrosynthetic analysis, we firstly started to synthesis

• -5''), 103.4 (C-5), 96.4 (C-3''), 87.4 (C-1'), 84.0 (C-4'), 73.2 (C-2'), 72.1 (C-3'), 62.2 (C-5'), 56.0 (OMe-4''), 55.5 (OMe-2''), 20.7 (Me-6'), 20.3 (Me-6''); HRMS (ESI) m/z: [M + Na]+ calcd for C21H24N2O10Na, 487.1329; found, 487.1327. Structures of kipukasins A–J. Retrosynthetic analysis of

Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction

• Yan Chen,
• Xiaoman Wang,
• Junchang Wang and
• You Yang

Beilstein J. Org. Chem. 2017, 13, 795–799, doi:10.3762/bjoc.13.79

• reported differentially protected ketoheptose building blocks may find further application in the preparation of structurally diverse D-manno-heptulose derivatives. Retrosynthetic analysis of D-manno-heptulose. Initial attempt on the synthesis of the C4 aldehyde from D-lyxose (5). Synthesis of

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• disaccharide branch at C3 of β-D-ManpNAcA and C3 of α-L-FucpNAc [15]. We established a total synthesis of the hexasaccharide repeat unit as a first step toward a detailed immunological analysis of S. pneumoniae 12F. Results and Discussion Retrosynthetic analysis. Initially, a convergent [3 + 3] synthesis of

Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2016, 12, 2865–2872, doi:10.3762/bjoc.12.285

• ) azapeptoid, (f) hydrazinopeptide and (g) hydrazinopeptoid. Some biologically active peptoids. Biologically active hydrazinopeptides and representation of the hydrazino turn. General structure of the acylhydrazino-peptomers synthesized in this study. Retrosynthetic analysis. Synthesis of hydrazides 3a–c

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• . Retrosynthetic analysis of the designed B-ring-modified analogues of brazilin. The synthetic challenge associated with the synthesis of 5 by IFCEA of 6 (above) and recent literature reports of cis-diastereoselective synthesis of related tetracyclic molecules via intramolecular Friedel–Crafts cyclization

Facile synthesis of indolo[3,2-a]carbazoles via Pd-catalyzed twofold oxidative cyclization

• Chao Yang,
• Kai Lin,
• Lan Huang,
• Wei-dong Pan and
• Sheng Liu

Beilstein J. Org. Chem. 2016, 12, 2490–2494, doi:10.3762/bjoc.12.243

• applied to the synthesis of malasseziazoles by Knölker et al. [14]. However, the main challenge in retrosynthetic analysis was to achieve the regioselective cyclizaion, since the formation of undesired regioisomeric monocyclized products would block the further cyclization. If the reaction follows the

• materials. The operational simplicity combined with the convenience for introducing substituents to the aromatic rings makes this method useful. Natural indolo[3,2-a]carbazole alkaloids. Retrosynthetic analysis of indolo[3,2-a]carbazoles. Reagents and conditions: (a) H2SO4, MeOH; (b) Ar-NH2, Pd(OAc)2, BINAP

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• economy; green organic synthesis; integer partitioning; reactions; probability; retrosynthetic analysis; ring construction strategy; Introduction The ring motif is a key feature in chemical structures that has long attracted the attention of synthetic organic chemists in their quest to implement novel

• greenness. In research practice, synthetic organic chemists rely on a combination of retrosynthetic analysis [91][92][93][94][95][96][97], similarity and analogy patterning to known reactions, bond dissociation energy and bond polarity analysis (forward and umpolung), chemical intuition, and random

• vast library of reactions that they are familiar with from personal experience or through their readings of the literature. Extending known reaction strategy and bond forming-bond breaking themes by analogy is a very useful method. Though retrosynthetic analysis is a powerful tool in the arsenal, its

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• . Synthesis of (±)-enduracididine (1) and (±)-allo-enduracididine (3). Synthesis of L-allo-enduracididine (3). Synthesis of protected L-allo-enduracididine 63. Synthesis of β-hydroxyenduracididine derivative 69. Synthesis of minosaminomycin (9). Retrosynthetic analysis of mannopeptimycin aglycone (77

Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs

• Arne Klinkebiel,
• Ole Beyer,
• Barbara Malawko and
• Ulrich Lüning

Beilstein J. Org. Chem. 2016, 12, 2267–2273, doi:10.3762/bjoc.12.219

• the Suzuki–Miyaura coupling [11]. A retrosynthetic analysis (Figure 3) of extended mono-functionalized triazinetricarboxylic acids 2 calls for tris(4-bromoaryl)-1,3,5-triazines 3 and boronic acids 4 with an additional carboxylic acid functionality. The respective methyl carboxylate of boronic acid 4

• , right). The two structures in the lower half have been calculated with B3LYP//6-31G*. Mono-substituted TATB linkers 1b–d were successfully employed in the isoreticular syntheses of PCN-6 MOFs [10]. Retrosynthetic analysis for extended TATBs 2: triple Suzuki coupling between tribromotriazines 3 and

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• bromides or aryl chlorides, but initial investigation with 6-bromo-THQs indicated that these were remarkably unreactive in cross-coupling reactions [14], and a reliable and scalable synthesis of the likely more reactive iodides was, therefore, sought. We first considered the retrosynthetic analysis shown