Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• course of this work, we discovered an unusual Payne-like rearrangement process that occurred in preference to the ring-opening of a hindered epoxide. Results and Discussion Our retrosynthetic analysis of lyconadin A is shown in Scheme 1. We reasoned that 1 could be formed by an alkylation cascade

• , future studies of the scope and limitations of Lewis acid promoted Payne rearrangement–ring-opening cascades could establish their utility in organic synthesis. Lyconadin A. Retrosynthetic analysis of 1. Synthesis of triether 15. Synthesis and attempted ring-opening of epoxide 17. Attempted protection of

Synthesis of 2,3-dihydronaphtho[2,3-d][1,3]thiazole-4,9-diones and 2,3-dihydroanthra[2,3-d][1,3]thiazole-4,11-diones and novel ring contraction and fusion reaction of 3H-spiro[1,3-thiazole-2,1'-cyclohexanes] into 2,3,4,5-tetrahydro-1H-carbazole-6,11-diones

• Lidia S. Konstantinova,
• Kirill A. Lysov,
• Ljudmila I. Souvorova and
• Oleg A. Rakitin

Beilstein J. Org. Chem. 2013, 9, 577–584, doi:10.3762/bjoc.9.62

• interested in developing a general method for the synthesis of naphtho- and anthraquinones from readily available 2-aminonaphtho- and anthroquinones as well as in the study of their chemical properties and side reactions. A retrosynthetic analysis of naphtho- and anthraquinones 1 and 2 led us to a conclusion

• solution of spiro compounds 1d or 2d (1 mmol) and triethylamine (0.17 mL, 1.20 mmol) in chlorobenzene (20 mL) was heated under reflux for 12 h. The solvent was evaporated under reduced pressure, and the residue was crystallized from hexane/CH2Cl2 mixture. Retrosynthetic analysis of 2,3-dihydronaphtho[2,3-d

Facile synthesis of benzothiadiazine 1,1-dioxides, a precursor of RSV inhibitors, by tandem amidation/intramolecular aza-Wittig reaction

• Krishna C. Majumdar and
• Sintu Ganai

Beilstein J. Org. Chem. 2013, 9, 503–509, doi:10.3762/bjoc.9.54

• [45][46][47][48][49][50][51], we have undertaken a study to synthesize 1,2,4-benzothiadiazine 1,1-dioxide derivatives using an intramolecular aza-Wittig reaction as the key step. Herein we report our results. Retrosynthetic analysis of the RSV inhibitors 5 and 6 relied on benzothiadiazine-3-one 1,1

• -dioxide 7, which can easily be obtained by simple hydrolysis of the benzothiadiazine 1,1-dioxide derivative 8. Construction of this six-membered sultam 8 was thought to be achieved by intramolecular aza-Wittig reaction of the o-azido derivative 9. The following retrosynthetic analysis led us to the

De novo synthesis of D- and L-fucosamine containing disaccharides

• Daniele Leonori and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 332–341, doi:10.3762/bjoc.9.38

• blocks Our retrosynthetic analysis of D-fucosamine envisioned the installation of the syn-1,2-diol unit by osmium-catalysed dihydroxylation of allylic ether A. It was anticipated that the conformation adopted by the molecule would allow for the formation of the required anti relationship between C3 and

• ), 41.7 (CH2Q), 30.5 (CH2N), 28.8 (CH2P), 24.8 (CH3), 24.5 (CH2O), 24.4 (CH3), 17.8 (CH3); LRMS–ESI (m/z): 453.2 [M + H+]; HRMS–ESI (m/z): [M + H+] calcd for C19H37N2O10, 453.244; found, 453.2468. Structure of some O-linked glycans found on the cell surface of P. aeruginosa. Retrosynthetic analysis of D

From bead to flask: Synthesis of a complex β-amido-amide for probe-development studies

• Kevin S. Martin,
• Cristian Soldi,
• Kellan N. Candee,
• Hiromi I. Wettersten,
• Robert H. Weiss and
• Jared T. Shaw

Beilstein J. Org. Chem. 2013, 9, 260–264, doi:10.3762/bjoc.9.31

• laser desorption/ionization mass spectrometry [14]. In the current synthesis, we set out to develop a concise and scalable solution-phase route to 1 and provide characterization data for 1 and all intermediate compounds. In our retrosynthetic analysis, we envisioned 1 coming from acylation of

• easily accessible for early stage studies of these compounds in vitro and in vivo using model organisms. p21 determines the fate of DNA-damaged [13] cells. Retrosynthetic analysis of LLW62 (1) from acid 7 (A) or aldehyde 11 (B). Attempted synthesis of aldehyde 4 from nitrile 6. (A) Synthesis of 4 from

Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• the retrosynthetic analysis of spiro-bicyclic type VI β-turn mimic 48, a disconnection at the lactam bond in the indolizidinone core was envisioned, which would give rise to a symmetric unit of two prolines linked enantioselectively via a two-carbon linkage at their α-carbons [55]. Such an approach

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• on transformation of the products of the discussed reactions of salicylaldehyde with enolates to biologically active compounds and natural products. Retrosynthetic analysis of chromane 1. General reaction of salicylaldehyde (5) and acetophenone (7) in the synthesis of flavan 10 and flavone 11

A new approach toward the total synthesis of (+)-batzellaside B

• Jolanta Wierzejska,
• Shin-ichi Motogoe,
• Yuto Makino,
• Tetsuya Sengoku,
• Masaki Takahashi and
• Hidemi Yoda

Beilstein J. Org. Chem. 2012, 8, 1831–1838, doi:10.3762/bjoc.8.210

• class of biologically potent piperidine alkaloids and related analogues. Examples of naturally occurring iminosugars. The chemical structures of (+)-batzellasides A–C (1a–c). Our previous approach to (+)-batzellaside B and retrosynthetic analysis for the new synthetic strategy. Reagents and conditions

Enantioselective total synthesis of (R)-(−)-complanine

• Krystal A. D. Kamanos and
• Jonathan M. Withey

Beilstein J. Org. Chem. 2012, 8, 1695–1699, doi:10.3762/bjoc.8.192

• organocatalytic O-nitrosoaldol as the key step. A retrosynthetic analysis for complanine is depicted in Scheme 1. The synthesis was initiated by preparation of homoconjugated all-Z-diene 1 (Scheme 2). Sequential olefin preparation by using Wittig chemistry, or selective polyyne reduction represent two traditional

• . Retrosynthetic analysis of (R)-(−)-complanine. Reagents and conditions: (a) Cs2CO3, CuI, TBAI, DMF, rt, 24 h, 91%; (b) H2 (1 atm), Lindlar catalyst, EtOAc, pyridine, rt, 24 h; (c) DMSO, (COCl)2, DCM, −78 °C, then; 1, −78 °C, 45 min, then, Et3N, 0 °C, 1.5 h, 86% from 2. Direct approach to amino alcohol 4

Automated synthesis of sialylated oligosaccharides

• Davide Esposito,
• Mattan Hurevich,
• Bastien Castagner,
• Cheng-Chung Wang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 1601–1609, doi:10.3762/bjoc.8.183

• of sialosides. (a) Synthesis sequence for the preparation of building blocks 4 and 5; (b) Retrosynthetic analysis for the preparation of 1. Reagents and conditions: (i) PhI(OAc)2, BF3·Et2O, CH2Cl2, −40 °C; then Ac2O, pyridine; (ii) N2H4·AcOH, DMF; (iii) CF3C(NPh)Cl, Cs2CO3, CH2Cl2, DCM, 66% over

Regioselective synthesis of 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives: A new drug-like heterocyclic scaffold

• Nikolay T. Tzvetkov,
• Harald Euler and
• Christa E. Müller

Beilstein J. Org. Chem. 2012, 8, 1584–1593, doi:10.3762/bjoc.8.181

• ) (Scheme 2). According to our retrosynthetic analysis (Scheme 1), and based on an efficient protocol for the regioselective N-alkylation of hydantoins, we applied a four-step procedure for the synthesis of differently substituted 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6-diones 23–29 (Scheme 3). The

Asymmetric total synthesis of smyrindiol employing an organocatalytic aldol key step

• Dieter Enders,
• Jeanne Fronert,
• Tom Bisschops and
• Florian Boeck

Beilstein J. Org. Chem. 2012, 8, 1112–1117, doi:10.3762/bjoc.8.123

• diastereoselectivity, with a slight preference (18% versus 15%) towards the anti-isomer xanthoarnol (Scheme 2).We now wish to present the first diastereo- and enantioselective, organocatalytic, asymmetric synthesis of smyrindiol. Results and Discussion Retrosynthetic analysis Previously the proline-catalyzed

• retrosynthetic analysis. Attempted proline catalyzed aldol reaction. Second retrosynthetic analysis. Asymmetric total synthesis of smyrindiol (1). Supporting Information Supporting Information File 77: Experimental procedures and characterization of compounds. Supporting Information File 78: NMR-spectra and

Aldol elaboration of 4,5,6,7-tetrahydroisoxazolo[4,3-c]pyridin-4-ones, masked precursors to acylpyridones

• Raymond C. F. Jones,
• Abdul K. Choudhury,
• James N. Iley,
• Mark E. Light,
• Georgia Loizou and
• Terence A. Pillainayagam

Beilstein J. Org. Chem. 2012, 8, 308–312, doi:10.3762/bjoc.8.33

• -tetrahydroisoxazolo[4,3-c]pyridin-4-one (8a) [19]. Ilicicolin H as an example of a 3-decalinoyl-4-hydroxypyridin-2-one metabolite. Aldol reactions of tetrahydroisoxazolopyridone 6. Reagents: (i) LDA–TMEDA, RCHO, THF, −20 °C; (ii) toluene, reflux, PTSA. Retrosynthetic analysis of a model 3-decalinyl-4,5,6,7

Derivatives of phenyl tribromomethyl sulfone as novel compounds with potential pesticidal activity

• Krzysztof M. Borys,
• Maciej D. Korzyński and
• Zbigniew Ochal

Beilstein J. Org. Chem. 2012, 8, 259–265, doi:10.3762/bjoc.8.27

• of the obtained compounds exhibit fungicidal activity. Retrosynthetic analysis of the designed target molecules. Synthetic routes for 4-chlorophenyl tribromomethyl sulfone (1). Halogenation/nitration sequence for 4-halogenphenyl methyl sulfones 4 and 4'. SNAr transformations of sulfone 6. Preparation

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• issue for which no solution existed at that time: The arylation of stabilized enolates. Indeed, the retrosynthetic analysis illustrated in Scheme 1 suggests that 1 could result from the cyclization of 3, which in turn would ensue through the union of fragments 4 and 5. These two subunits were prepared

• retrosynthetic analysis of fredericamycin A. Assembly of the isoquinolone segment of fredericamycin. Synthesis of a naphthalide precursor to the quinoid moiety of fredericamycin. Palladium-mediated cyclization of a fredericamycin model system. Synthesis of the precursor of fredericamycin and the facile air

Efficient syntheses of 25,26-dihydrodictyostatin and 25,26-dihydro-6-epi-dictyostatin, two potent new microtubule-stabilizing agents

• María Jiménez,
• Wei Zhu,
• Andreas Vogt,
• Billy W. Day and
• Dennis P. Curran

Beilstein J. Org. Chem. 2011, 7, 1372–1378, doi:10.3762/bjoc.7.161

• roughly comparable to those of dictyostatin (1a) and 6-epi-dictyostatin (1b). Here we report the full details of the synthesis of 3a and 3b. Results and Discussion Figure 2 shows key aspects of the retrosynthetic analysis to make analogs 3a and 3b, which follows after the successful streamlined route to

• C25–C26. Retrosynthetic analysis for 3a and 3b. Synthesis of top fragment 8 (C18–C26). Synthesis of middle fragment 7 (C10–C17). Synthesis of bottom fragments 6a,b (C1–C9). Coupling of the top and middle fragments. Coupling with the bottom fragment and end game. Supporting Information Supporting

A new phenylethyl alkyl amide from the Ambrostoma quadriimpressum Motschulsky

• Guolei Zhao,
• Chao Yang,
• Bing Li and
• Wujiong Xia

Beilstein J. Org. Chem. 2011, 7, 1342–1346, doi:10.3762/bjoc.7.158

• positive optical rotation ([α]20D +38.5 (c 0.13, CHCl3)). To confirm the absolute configuration at C(10), an asymmetric total synthesis was performed. Synthesis of (10R)-10-hydroxy-N-phenethyloctadecanamide (1) The retrosynthetic analysis of compound 1 is outlined in Scheme 2. The target molecule is

• ; HRMS–ESI (m/z): [M + H]+ calcd for C26H45NO2, 404.3529; found, 404.3529. Chemical structure of compound 1 and mass spectral analysis. Retrosynthetic analysis of (R)-1. (a) BnOH, H2SO4; NaNO2, AcOH; CH2N2, 35% in 3 steps. (b) TBDPSCl, imidazole, 100%. (c) Pd/C, H2; BH3·THF, 95% in 2 steps. (d) TBDMSCl

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

• Verónica Guilarte,
• M. Pilar Castroviejo,
• Estela Álvarez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 1255–1260, doi:10.3762/bjoc.7.146

• between the methoxy and the halide groups, irrespective of the nature of the halogen atom (chloro or bromo) (Table 1, entries 3 and 4). Having an efficient protocol for the synthesis of dimethoxyhaloiodobenzene derivatives 4, and with the retrosynthetic analysis outlined in Scheme 1 in mind, we tackled

• B gave rise to better selectivities and yields of the desired alkynes 5–7 (Table 2, entries 4,6,10,12,16 and 18). According to our retrosynthetic analysis (Scheme 1), the final step to achieve the benzofuran derivatives should be the incorporation of the hydroxy group followed by in situ

• dihydroxybenzofuran derived natural products. Retrosynthetic analysis of 4,n-dimethoxy-substituted benzo[b]furans. Deprotonative zincation of 3-haloanisoles 1. Synthesis of methoxy-substituted 3-halo-2-iodoanisoles 4. Synthesis of dimethoxy-substituted o-alkynylhaloarenes 5–7. Synthesis of dimethoxy-substituted benzo

Directed aromatic functionalization

• Victor Snieckus

Beilstein J. Org. Chem. 2011, 7, 1215–1218, doi:10.3762/bjoc.7.141

• exception [32][33][34], to rationalize ortho selectivity. The aromatic ring annulative chemistry, which can be achieved by C–H-activation mediated processes, perhaps best exemplified by gold-catalyzed reactions [35][36], is astonishing and defies retrosynthetic analysis. While as yet mostly empirically

One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

• Charlotte F. Gers,
• Julia Rosellen,
• Eugen Merkul and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1173–1181, doi:10.3762/bjoc.7.136

• [48]. Our retrosynthetic analysis (Scheme 3) suggests that a wide range of N-heterocycle-substituted azulenes should be accessible through Michael addition–cyclocondensation of azulenylynones with binucleophiles. Azulenylynones in turn could be simply disconnected by our glyoxylation–decarbonylative

• Sonogashira coupling. Retrosynthetic analysis of N-heterocyclic substituted azulenes by a one-pot four-component approach. Three-component synthesis of azulenyl- and guaiazulenylynones 3 by glyoxylation–decarbonylative Sonogashira coupling sequence. Four-component synthesis of pyrimidylazulenes 5 by

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

• María Martín-Rodríguez,
• Carmen Nájera,
• José M. Sansano,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2011, 7, 988–996, doi:10.3762/bjoc.7.111

• )–ylide complex and tert-butyl acrylate computed at ONIOM(B3LYP/LanL2DZ:UFF) level of theory. High-level and low-level layers are represented as ball & stick and wireframe models, respectively. Grey numbers in parentheses represent Mulliken charges. Distances are in Å. Retrosynthetic analysis of antiviral

A racemic formal total synthesis of clavukerin A using gold(I)-catalyzed cycloisomerization of 3-methoxy-1,6-enynes as the key strategy

• Jae Youp Cheong and
• Young Ho Rhee

Beilstein J. Org. Chem. 2011, 7, 740–743, doi:10.3762/bjoc.7.84

• compatible with the acid-sensitive functional group. Further application of the gold(I)-catalyzed cycloisomerization reaction of 3-methoxy-1,6-enynes to the enantioselective synthesis of more structurally complex cycloheptane natural products is in progress, and will be reported in due course. Retrosynthetic

• analysis. Preparation of compound 5. Synthesis of the cycloheptenone 4. Completion of the formal synthesis of clavukerin A. Supporting Information Supporting Information File 144: Experimental section for the preparation of compounds 2–12, and 1H and 13C NMR spectra for all new compounds

A gold-catalyzed alkyne-diol cycloisomerization for the synthesis of oxygenated 5,5-spiroketals

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2011, 7, 570–577, doi:10.3762/bjoc.7.66

• -shoot of our program devoted to the synthesis of functionalized alkynes by fragmentation reactions [23][24][25][26][27], we became interested in the application of alkyne-diol cycloisomerization to the synthesis of the cephalosporolides and other oxygenated spiroketals. Our retrosynthetic analysis of

• spiroketal motifs. Spiroketal-containing cephalosporolide natural products. Cyclocondensation vs. cycloisomerization for the synthesis of spiroketals. Retrosynthetic analysis of cephalosporolide H. Key precedents for the desired cycloisomerization. Proposed cycloisomerization with acetal hydrolysis

Reciprocal polyhedra and the Euler relationship: cage hydrocarbons, C_nH_n and closo-boranes [B_xH_x]²⁻

• Michael J. McGlinchey and
• Henning Hopf

Beilstein J. Org. Chem. 2011, 7, 222–233, doi:10.3762/bjoc.7.30

• . Synthesis of [3]prismane 9 by Katz. Synthesis of cubane 10 by Eaton. Synthesis of cubane 10 by Pettit. Failed routes to [5]-prismane 11. Synthesis of [5]prismane 11 by Eaton. Retrosynthetic analysis for several approaches to dodecahedrane 16. Paquette´s synthesis of dodecahedrane 16. Prinzbach´s synthesis

Stereoselective synthesis of four possible isomers of streptopyrrolidine

• Debendra K. Mohapatra,
• Barla Thirupathi,
• Pragna P. Das and
• Jhillu S. Yadav

Beilstein J. Org. Chem. 2011, 7, 34–39, doi:10.3762/bjoc.7.6

• (4S,5S)-streptopyrrolidine (4) in a concise and highly efficient manner via a highly stereoselective aldol type reaction and Lewis acid mediated lactamization as the key reactions. A retrosynthetic analysis for streptopyrrolidine is depicted in Scheme 1. The synthesis was initiated from D

• ) and (4S,5S)-streptopyrrolidine (4). Δδ = (δS−δR) × 103 for (S)- and (R)-MTPA esters of compound 8b. Retrosynthetic analysis. Reagents and conditions: (a) LDA, EtOAc, THF, −78 °C, 4 h, 80% (8a:8b = 3:2); (b) BF3·OEt2, (1-ethoxyvinyloxy)trimethylsilane, CH2Cl2, −78 °C, 2 h, 85% (exclusively 8b); (c