Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• both art and photography at Illinois Institute of Technology, but science and scientists ended up deciding me. It started with Chem. 237, Organic Chemistry. This course was taught by Pete Johnson, who introduced me to retrosynthetic analysis, and in the process showed me how I could achieve the

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• phospinooxazoline ligands. Asymmetric hydrogenation with iridium-NeoPHOX catalysts [19]. Employing L-valine as a starting material for C5 substituted oxazoline. Retrosynthetic analysis for NeoPHOX ligands derived from serine and threonine. Crystal structures of selected Ir-complexes. Hydrogen atoms, COD and BArF

• anions were omitted for clarity. Retrosynthetic analysis for NeoPHOX ligands. Synthesis of 1st generation NeoPHOX Ir-complexes [19]. Synthesis of a C(5)-disubstituted NeoPHOX-Ir complex. Revisited synthetic strategy for the preparation of a threonine-based NeoPHOX ligand. Undesired β-lactam formation

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• reported in due course. Keramaphidin B (1). Retrosynthetic analysis of keramaphidin B. Enantio- and diastereoselective bifunctional thiourea 12 organocatalysed Michael addition. (a) CO(OMe)2, LHMDS, THF, −78 °C to rt, 83%; (b) 20 mol % 12, toluene, −20 °C, 24 h, 95:5 dr (13:14), 90:10 er for 13, 99% yield

Catalytic asymmetric formal synthesis of beraprost

• Yusuke Kobayashi,
• Ryuta Kuramoto and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285

• Our retrosynthetic analysis for 2 is shown in Scheme 1, with the derivatization of 2 to beraprost (1) having already been reported. We planned to introduce the ester side chain on the aromatic ring at a later stage, utilizing radical-mediated reactions with acrylate [22] when the functional group (X

• (1). Retrosynthetic analysis of beraprost (1). Preparation of Michael precursors 7 and 8. First attempt at the synthesis of 2 from 6. Achievement of a formal synthesis of 2. Optimization of asymmetric intramolecular oxa-Michael reaction. Supporting Information Supporting Information File 476

Total synthesis of panicein A₂

• Lili Yeung,
• Lisa I. Pilkington,
• Melissa M. Cadelis,
• Brent R. Copp and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 1991–1996, doi:10.3762/bjoc.11.215

• with the earlier report that stated 5 exhibits in vitro cytotoxicity against a number of cell lines (ED50 = 5 μg/mL). Members of the panicein family of aromatic sesquiterpenoids. Proposed biogenesis of panicein A2 (5). Retrosynthetic analysis of panicein A2 (5). Synthesis of ketone 13. Synthesis of

Design and synthesis of propellane derivatives and oxa-bowls via ring-rearrangement metathesis as a key step

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2015, 11, 1727–1731, doi:10.3762/bjoc.11.188

• target molecule, eventually to arrive at simple starting materials by working in an opposite direction to a chemical synthesis. The ‘retrosynthetic analysis’ was first introduced by E. J. Corey and defined as “it is a problem solving technique for transforming the structure of a synthetic target molecule

• to a sequence of progressively simpler structures along a pathway which ultimately leads to a simple or commercially available starting materials for a chemical synthesis” [1] . Generally, this type of retrosynthetic analysis has been used to design [2][3][4][5][6] the target molecule. However, a

Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha,
• Ongolu Ravikumar and
• Jadab Majhi

Beilstein J. Org. Chem. 2015, 11, 1503–1508, doi:10.3762/bjoc.11.163

• ; found, 224.1041. Retrosynthetic analysis of tricyclic amide 1. Molecular crystal structure of compound 11b. Synthesis of tricyclic ketone 4. Beckmann rearrangement of oximes 8a and 8b. Beckmann rearrangement reaction in a single step. Synthesis of ring-rearrangement precursors. Synthesis of Beckmann

Spiro annulation of cage polycycles via Grignard reaction and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Mohammad Saifuddin,
• Rashid Ali and
• Gaddamedi Sreevani

Beilstein J. Org. Chem. 2015, 11, 1367–1372, doi:10.3762/bjoc.11.147

• -closing metathesis (RCM) are considered as viable options. The retrosynthetic analysis to the target bis-spiro-cage compound 7 is shown in Figure 2. The target compound 7 could be obtained from O-allylation of the Grignard addition product 11 followed by the two-fold RCM sequence. The required cage dione

• synthesis of interesting cage molecules are in progress. Structures of diverse biologically as well as theoretically interesting molecules. Retrosynthetic analysis of bis-spiro-pyrano cage compound 7. (a)Optimized structure of 12, (b) optimized structure of 13. (a) Optimized structure of 18, (b) optimized

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• 1a. For selected parameters see Supporting Information File 1. Enaminone-based synthesis of (S)-cuspareine. The approaches to 2-aroylmethylidene-1,2,3,4-tetrahydroquinolines 1. The retrosynthetic analysis of the starting substrates for C–N cross-coupling. The synthesis of methyl 3-phenylpropionates

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• employed 'dimeric' T–T phosphoramidites 6 [38] for the automated synthesis of NAA-modified oligonucleotides; new 'dimeric' A–T phosphoramidites 7 as target structures of this study (DMTr = 4,4'-dimethoxytrityl). Retrosynthetic analysis of target phosphoramidites (S)-7 and (R)-7 (BOM = benzyloxymethyl

A carbohydrate approach for the formal total synthesis of (−)-aspergillide C

• Pabbaraja Srihari,
• Namballa Hari Krishna,
• Ydhyam Sridhar and
• Ahmed Kamal

Beilstein J. Org. Chem. 2014, 10, 3122–3126, doi:10.3762/bjoc.10.329

• approach has been a conventional strategy to achieve the total synthesis of complex, natural products with known handedness. Herein we disclose our strategy for the formal total synthesis of (−)-aspergillide C in a concise manner following the chiron approach. Retrosynthetic Analysis Through a

• retrosynthetic analysis, we envisaged that the macrolide 3 could be prepared from the seco acid 4 which can be easily accessed from 5 in five steps (Scheme 1). Compound 5, in turn, can be synthesized from commercially available tri-O-acetyl-D-galactal (6) and alkyne 7 through a Ferrier-type C-glycosylation

• tri-O-acetyl-D-galactal. A C-glycosidation, Trost’s hydrosilylation and protodesilylation protocol have been used as the key steps for achieving the formal total synthesis. Structures of aspergillides. Key NOESY correlations observed in compound 11. Retrosynthetic analysis for (−)-aspergillide C

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• quaternary centers, two of which are stereogenic. Being a hydrocarbon, (−)-thujopsene (10) has few natural handles for retrosynthetic analysis. Inspired by the complexity of this relatively small natural product, several total syntheses of racemic 10 have been reported [25][26][27][28][29] along with at

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

• 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

• chemical shifts in 1’. Δδ corresponds to the difference in chemical shift for natural and synthetic products (Δδ = δ(synthetic) – δ(natural)). Retrosynthetic analysis. Synthesis of 2,3-cis-astakolactin. MNBA-mediated lactonization. Synthesis of 2,3-trans-astakolactin. Yields of astakolactin (1) using

Scalable synthesis of 5,11-diethynylated indeno[1,2-b]fluorene-6,12-diones and exploration of their solid state packing

• Bradley D. Rose,
• Peter J. Santa Maria,
• Aaron G. Fix,
• Chris L. Vonnegut,
• Lev N. Zakharov,
• Sean R. Parkin and
• Michael M. Haley

Beilstein J. Org. Chem. 2014, 10, 2122–2130, doi:10.3762/bjoc.10.219

• overcome the synthetic roadblock that Scheme 1 represented. The improved synthetic route to 8 arises from a retrosynthetic analysis of the current method to prepare IF derivatives [9][10][11][13]. The needed modification must include halogens at the 5 and 11 positions for subsequent functionalization, such

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• Information File 1). Retrosynthetic analysis of the bifunctional cytidine derivative 1 for functionalization of a periodate-oxidized RNA library. Introduction of the triazolyl moiety into the uridine derivative 7 generating synthon 3. I: 4 equiv POCl3, 16 equiv triazole, 20 equiv NEt3, MeCN, 60 min at 0 °C

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• . From a synthetic point of view, the target nucleosides could be synthesized from either 1,2,3,5-tetra-O-benzoyl-2-C-β-methyl-D-ribofuranose (5) (route A) or 5-deoxy-1,2,3-tri-O-acetyl-β-D-ribofuranose (6) (route B). The corresponding retrosynthetic analysis is shown in Figure 2. In synthetic route (A

• synthesis of versatile 5′-deoxy-2′-C-branched nucleosides. Structures of trachycladine A and B. Retrosynthetic analysis of trachycladines A and B. The X-ray crystal structural of 1-O-methyl-3-O-(2,4-dichlorobenzyl)-5-deoxy-α-D-ribofuranose (9). Synthesis of 5-deoxy-1-O-acetyl-2,3-di-O-benzoyl-2-C-β-methyl-D

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• analog that still exhibits similar inhibitory activity on hedgehog-signaling. For the sake of brevity of the overall synthetic sequence we defined carbacyclopamine analog 2 (see Figure 1) as our primary target. Results and Discussion A retrosynthetic analysis identified diazo compound 3 as a key

• application in the rational design of new hedgehog inhibitors based on lead structure 2. Future work will focus on the synthesis of carbacyclopamine analogs with a piperidine F-ring and their biological investigation. Structures of cyclopamine (1) and carbacyclopamine analog 2. Retrosynthetic analysis of

Efficient routes toward the synthesis of the D-rhamno-trisaccharide related to the A-band polysaccharide of Pseudomonas aeruginosa

• Aritra Chaudhury,
• Sajal K. Maity and
• Rina Ghosh

Beilstein J. Org. Chem. 2014, 10, 1488–1494, doi:10.3762/bjoc.10.153

• pivotal intermediates 1a and 1b which were obtained using previously reported methods [40][41] and then proceeding forward to the monomeric building blocks required according to the retrosynthetic analysis (Figure 2). The procedures used and the results obtained to reach the intermediate targets have been

• -manno-trisaccharide derivative (bearing 4,6-O-benzylidene protection on each mannose unit) offer great potential in future oligosaccharide syntheses based on 6-deoxy hexoses. Repeating unit of the A-band polysaccharide of P. aeruginosa. Retrosynthetic analysis. Preparation of the monomeric building

Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids

• Angélica de Fátima S. Barreto,
• Otilie E. Vercillo,
• Ludger A. Wessjohann and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2014, 10, 1017–1022, doi:10.3762/bjoc.10.101

• . It was decided to keep at least one benzyl group in the structure of the peptoids and vary the isopropyl and isobutyl groups, thus maintaining a greater similarity with the structure of the San A depsipeptide. The retrosynthetic analysis of the depsipeptoids (Scheme 1) shows that the proposed

• biological activities. Sansalvamide A (1) and its depsipeptoid analogues (2). Generic structures of (a) peptide, (b) peptoid, (c) depsipeptide and (d) depsipeptoid. Structures of six pentadepsipeptoid analogues of San A. Retrosynthetic analysis of the cyclic depsipeptoids. Synthesis of acyclic depsipeptoids

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• -hydroxy-β-amino acid) in 2a is present in several biologically active compounds such as taxol, balanol and bestatin. Therefore, this methodology could be potentially exploited for the synthesis of the chiral segment of these compounds. Microginin (1) and (2S,3R)-AHDA (2a). Retrosynthetic analysis of AHDA

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• Discussion Retrosynthetic analysis of target molecules One common feature of activated biosynthesis intermediate analogues such as 5a is their relative low stability. In the natural context, PKS intermediates are quickly processed by downstream domains or tailoring enzymes. However, if analogues are

• configuration of the double bond in the dehydration product is presently unknown. In a previous study, we have shown that BorDH3 only accepts surrogates with the shown 2D,3D-configuration if incubated with simple 3-hydroxy-2-methyl-SNAc pentanoates [7][12]. Retrosynthetic analysis of surrogate substrates for

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• ); HRMS (EI) m/z: [M]+ calcd for C18H14N2OF, 293.1090; found, 293.1070. Natural products containing the β-carboline skeletal. COSY and HSQC of 8a and 7a. Retrosynthetic analysis of 6. Plausible mechanism of the oxidative amidation for 9. Synthesis of α-ketoamide 9. Synthesis of dihydroeudistomin Y

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• from methionine and studies towards the preparation of glutamic and aspartic acid derived heterocycles are presented. Following the retrosynthetic analysis in Figure 2 the relative configuration of B (cis/trans) should be controlled through targeted protecting group (PG) manipulation: Reduction of the

• other pharmacologically relevant targets on a gram scale. Natural products and other bioactive piperidine derivatives of type B. Retrosynthetic analysis of piperidines B (X = OH or leaving group, PG = protecting group). Synthesis of the protected amino acids 2. (a) KOH for 1b. b) PG–X = Cbz–Cl (1a–c

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• of the crucial C9–C10 bond (Scheme 1) [35]. In this paper we present a full report on this synthesis [36] as well as further synthetic studies towards the application of the developed strategy to the total synthesis of B-seco limonoid natural products. Results and Discussion Retrosynthetic analysis

• precursor 30 and possible transition state involved in the Ireland–Claisen rearrangement. Conformations of rearrangement precursors 66 and 77 and possible transition states involved in the Ireland–Claisen rearrangements. R = MOM. Retrosynthetic analysis of the B-seco limonoid framework employing a [3,3

• ]-sigmatropic rearrangement for formation of the C9–C10 bond. R = Me or CO2H, LG = leaving group. Retrosynthetic analysis of the B-seco limonoid scaffold employing a Claisen rearrangement as key step for formation of the C9–C10 bond. PG = protecting group, LG = leaving group. Synthesis of alcohols 19, 20 and 22

Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach

• Andivelu Ilangovan and
• Shanmugasundar Saravanakumar

Beilstein J. Org. Chem. 2014, 10, 127–133, doi:10.3762/bjoc.10.9

• ). The spectral data is in accordance with the published data for natural dasyclamide [7] which further confirms the structure of the natural product. Synthesis of gigantamide A As given in the retrosynthetic analysis and based on the preference in literature for the preparation of jatropham by

• . Retrosynthetic analysis: A unified synthetic approach for the synthesis of grandiamide D, dasyclamide and gigantamide A. Preparation of N-(4-aminobutyl)cinnamamide. Synthesis of (±)-grandiamide D. Asymmetric synthesis of natural (+)-grandiamide D. Various approaches for the synthesis of (E)-N-(4-cinnamamidobutyl