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

Brønsted acid-promoted azide–olefin [3 + 2] cycloadditions for the preparation of contiguous aminopolyols: The importance of disiloxane ring size to a diastereoselective, bidirectional approach to zwittermicin A

• Hubert Muchalski,
• Ki Bum Hong and
• Jeffrey N. Johnston

Beilstein J. Org. Chem. 2010, 6, 1206–1210, doi:10.3762/bjoc.6.138

• traditional 6-membered dialkoxysilane. The anti,anti-selectivity observed in this transformation provides a foundation for the straightforward preparation of the aminopolyol backbone of (−)-zwittermicin A using a bidirectional chain functionalization strategy. Retrosynthetic analysis outlining the

A bivalent glycopeptide to target two putative carbohydrate binding sites on FimH

• Thisbe K. Lindhorst,
• Kathrin Bruegge,
• Andreas Fuchs and
• Oliver Sperling

Beilstein J. Org. Chem. 2010, 6, 801–809, doi:10.3762/bjoc.6.90

• strategy [25] was applied to connect the monosaccharide and the trisaccharide part of the bivalent glycopeptide target structure 1 (Figure 2). Accordingly, retrosynthetic analysis of 1 leads to the 2-azidoethyl glycosides 2 and 5, with the azido group masking an amino function; two pentaglycine spacer

Synthesis of gem-difluoromethylenated analogues of boronolide

• Jing Lin,
• Xiao-Long Qiu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2010, 6, No. 37, doi:10.3762/bjoc.6.37

• the conjugated double bond as an acceptor with minimum steric change. In this article we describe the concise synthesis of gem-difluoromethylenated analogues 4–7 of boronolide. Results and Discussion The retrosynthetic analysis of the target molecules 4–7 is outlined in Scheme 1. We envisioned that

• constructed by diastereoselective propargylation of the aldehyde. According to the retrosynthetic analysis our synthesis embarked from aldehyde 9, which was prepared from commercially available D-glucono-δ-lactone (8) in six steps, based on the reported route [15] (Scheme 2). The synthesis of the fluorine

• and the efficient construction of α,β-unsaturated-δ-lactones 15a–b via the BAIB/TEMPO-procedure. Boronolide (1), boronolide analogues 2–3 and gem-difluoromethylenated analogues 4–7. Retrosynthetic analysis of target molecules 4–7. Synthesis of target molecules 4–5. Synthesis of target molecules 6–7

A short and efficient synthesis of valsartan via a Negishi reaction

• Samir Ghosh,
• A. Sanjeev Kumar and
• G. N. Mehta

Beilstein J. Org. Chem. 2010, 6, No. 27, doi:10.3762/bjoc.6.27

• , 138.2, 131.54, 131.1, 131.0, 129.3,128.8, 128.2, 127.4, 126.7, 70.3, 63.4, 49.9, 32.9, 28.05, 27.3, 22.2, 20.6, 14.2; ESIMS: m/z calcd [M]+: 435; found: 436 [M+H]+; HRMS (ESI): m/z calcd [M]+: 435.5187; found: 435.5125 [M]+ Valsartan. Retrosynthetic analysis of 8. (a) Et3N, CH2Cl2, 0 °C, 95%; (b) NaH

A short synthesis of (±)-cherylline dimethyl ether

• Bhima Y. Kale,
• Ananta D. Shinde,
• Swapnil S. Sonar,
• Bapurao B. Shingate,
• Sanjeev Kumar,
• Samir Ghosh,
• Soodamani Venugopal and
• Murlidhar S. Shingare

Beilstein J. Org. Chem. 2009, 5, No. 80, doi:10.3762/bjoc.5.80

• are Michael addition, radical azidonation of aldehydes [18], Curtius rearrangement, and reduction of an isocyanate intermediate followed by Pictet–Spengler cyclization. Results and Discussion Our retrosynthetic analysis of (±)-cherylline dimethyl ether (5) is depicted in Scheme 1. It can be

• -1,2,3,4-tetrahydroisoquinolines. Retrosynthetic analysis of 5. (a) 1,2-Dimethoxybenzene, TFA, reflux, 3 h, 90%; (b) DIBAL-H, CH2Cl2, −78 °C, 3 h, 65%; (c) (i) NaN3, ICl, acetonitrile, CH2Cl2, 0–5 °C (ii) toluene, 110 °C, 1 h, 65%; (d) LiAlH4, THF, reflux, 24 h, 90% (e) HCHO, acetic acid, 90 °C, 2 h, 45

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

A short stereoselective synthesis of (+)-(6R,2′S)-cryptocaryalactone via ring- closing metathesis

• Palakodety Radha Krishna,
• Krishnarao Lopinti and
• K. L. N. Reddy

Beilstein J. Org. Chem. 2009, 5, No. 14, doi:10.3762/bjoc.5.14

• moiety [36][37], and herein we describe a short and efficient synthesis of cryptocaryalactone 1. Results and Discussion Retrosynthetic analysis Retrosynthetic analysis (Figure 2) reveals that compound 1 could be synthesized from bis-olefin 6 by a ring-closing metathesis reaction, while the bis-olefin

Sordarin, an antifungal agent with a unique mode of action

• Huan Liang

Beilstein J. Org. Chem. 2008, 4, No. 31, doi:10.3762/bjoc.4.31

• overall yield of 2%. Mander’s synthesis of sordaricin As early as 1991, Mander reported model studies [24][25] for sordaricin synthesis using intramolecular [4+2] cycloaddition, and this work culminated in a total synthesis of Sordaricin in 2003 [14][15]. Scheme 4 depicts Mander’s retrosynthetic analysis

Tether- directed synthesis of highly substituted oxasilacycles via an intramolecular allylation employing allylsilanes

• Peter J. Jervis and
• Liam R. Cox

Beilstein J. Org. Chem. 2007, 3, No. 6, doi:10.1186/1860-5397-3-6

• results with those for the Ph substrate, 4b, which represents one of the more sterically demanding substituents. Results and discussion The desired cyclisation precursors 4a and 4b were prepared using our well-established method. [3] The retrosynthetic analysis for the anti series of products is outlined

Reaction of benzoxasilocines with aromatic aldehydes: Synthesis of homopterocarpans

• Míriam Álvarez-Corral,
• Cristóbal López-Sánchez,
• Leticia Jiménez-González,
• Antonio Rosales,
• Manuel Muñoz-Dorado and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2007, 3, No. 5, doi:10.1186/1860-5397-3-5

• trans-2-(2-pivaloyloxyphenyl)-3-vinylchroman prepared through Sakurai reaction. In this way we have outlined an alternative synthetic strategy for the preparation of non natural analogs of the pterocarpans with promising biologic activities. Retrosynthetic analysis for the homopterocarpan skeleton

Synthesis and glycosidase inhibitory activity of new hexa- substituted C8-glycomimetics

• Olivia Andriuzzi,
• Christine Gravier-Pelletier,
• Gildas Bertho,
• Thierry Prangé and
• Yves Le Merrer

Beilstein J. Org. Chem. 2005, 1, No. 12, doi:10.1186/1860-5397-1-12

• glycosidases have been carried out. For these C8-glycomimetics, weak activities were observed, which can probably be explained by a too high conformational flexibility of such structures. Experimental See Supporting Information File 1. Sugars, iminosugars and carbasugars. Retrosynthetic analysis. 1D proton NMR