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

A unified approach to the important protein kinase inhibitor balanol and a proposed analogue

• Tapan Saha,
• Ratnava Maitra and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2013, 9, 2910–2915, doi:10.3762/bjoc.9.327

• remains important. A similar target is the closely related natural product ophiocordin (2). Herein, we describe a general approach to some of these targets. Results and Discussion The key feature of our retrosynthetic analysis (Figure 2) is the identification of the dehydro derivative of balanol 4 as the

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• can produce useful amounts of this important compound as well as novel isomers. Results and Discussion Retrosynthetic analysis A retrosynthetic analysis of RvD2 (1) is shown in Scheme 1. It was envisaged that the target compound 1 could be secured via a Sonogashira coupling to form the C11–C12 bond

• RvD2 (1) has been completed using a common linchpin Wittig reaction. Using this approach, we were able to prepare sufficient quantities of this important inflammation resolving compound for further biological evaluation. Structures of resolvins D1 (1) and D2 (2). Retrosynthetic analysis of RvD2 (1

The total synthesis of D-chalcose and its C-3 epimer

• Jun Sun,
• Song Fan,
• Zhan Wang,
• Guoning Zhang,
• Kai Bao and
• Weige Zhang

Beilstein J. Org. Chem. 2013, 9, 2620–2624, doi:10.3762/bjoc.9.296

• retrosynthetic analysis of I and I′ is presented in Scheme 1. Diol II and II′ arose from a Sharpless asymmetric dihydroxylation that form the C2 stereogenic center. The installation of the C3 stereocenter on vinyl ether III was proposed to utilize a Grignard reaction followed by chromatographic separation

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• ][49][50]. Employing other aldehydes instead of pentadecanal our straightforward route should also allow the synthesis of analogues of jaspine B. Structure of jaspine B 1 and its stereoisomers 2–4. Retrosynthetic analysis of jaspine B leading to pentadecanal and an alkoxyallene. Synthesis of racemic

Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• products with tetramic acid fragments we embarked on the development of a concise and modular approach towards integramycin and related natural products. According to the retrosynthetic analysis, which is outlined in Figure 2, the target molecule may be assembled from an appropriate spiroketal advanced

• , Microbial drugs). Retrosynthetic analysis of integramycin. Synthesis of the aromatic subunit. Sharpless epoxidation/Myers alkylation approach to the C16–C22 carboxylic acid fragment. Coupling of the fragments and spiroketalization. Supporting Information Supporting Information File 527: Experimental

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• product. On the basis of the abovementioned analysis, a retrosynthetic analysis of (8S,8aS)-5 is displayed in Scheme 5, which features the formation of the fused pyrrolidine ring from the but-3-ene-1-yl group, the expected trans-diastereoselective methylation as the key step, and protected (R)-3

• axial addition of methylmagnesium iodide to bicyclic keto-lactam 7. Holmes’ exclusive trans-diastereoselective methylation of N-Cbz-protected piperidin-3-one 8. Our plan for the trans-diastereoselective methylation of keto-lactam 10. Retrosynthetic analysis of (8S,8aS)-8-hydroxy-8-methylindolizidin-5

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• discovery research. Several natural occurring anthracycline antibiotics. Total synthesis of daunomycinone 6 according to Hansen. Synthesis of simplified anthracycline derivatives. Retrosynthetic analysis of anthracycline aglycone mimics. Si: any silyl group. Synthetic route for the synthesis of various

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• any racemization and obtaining N-protected compounds which may be useful for further transformations. In order to illustrate the efficiency of our method, we were interested in extending this methodology to quinolizidine privileged structures. Our retrosynthetic analysis is shown in Scheme 2. We

• , 168.1387. Previously reported approach from β-aminoynones for the synthesis of pyridones. Retrosynthetic analysis of (−)-epimyrtine. Synthesis of (−)-epimyrtine. Supporting Information Supporting Information File 542: Spectra of new compounds. Acknowledgements We thank the Program Ciências Sem Fronteiras

A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• ). Retrosynthetic analysis for (−)-oxyphyllol (1) and structures of the guaiane sesquiterpenes (+)-orientalol E (2) and (−)-englerin A (5). Attempted selective deoxygenation of diol 7. a) 1 mol % K2OsO4, NMO, acetone, water, THF, rt, 97%, diastereomeric ratio = 2:1 (ref. [6]); b) PhOC(S)Cl, pyridine, CH2Cl2, 0 °C

Stereoselective synthesis of the C79–C97 fragment of symbiodinolide

• Hiroyoshi Takamura,
• Takayuki Fujiwara,
• Isao Kadota and
• Daisuke Uemura

Beilstein J. Org. Chem. 2013, 9, 1931–1935, doi:10.3762/bjoc.9.228

• Julia–Kocienski olefination as the coupling reaction. The new retrosynthetic analysis of the C79–C97 fragment 8 is described in Scheme 2. We envisaged that the diol 8 could be synthesized by the Julia–Kocienski olefination [12][13][14] between aldehyde 9 and 1-phenyl-1H-tetrazol-5-yl (PT)-sulfone 10 and

• elucidation is currently underway and will be reported in due course. Structure of symbiodinolide (1). Our previous synthesis of the C79–C96 fragment 7. Retrosynthetic analysis of the C79–C97 fragment 8. Synthesis of aldehyde 20. Synthesis of PT-sulfones 23 and 24. Synthesis of the C79–C97 fragment 27. Julia

Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step

• James C. Anderson,
• Andreas S. Kalogirou,
• Michael J. Porter and
• Graham J. Tizzard

Beilstein J. Org. Chem. 2013, 9, 1737–1744, doi:10.3762/bjoc.9.200

• . Schematic nitro-Mannich reaction. Retrosynthetic analysis of piperazirum. (a) iBuMgCl, Et2O, −78 °C; (b) KOH, EtOH/H2O, 100 °C; (c) (COCl)2. (a) Li(Et3BH), THF, rt then 14, CF3CO2H, −78 °C, dr 70:30; (b) (CF3CO)2O, Py, CH2Cl2, 0 °C to rt; (c) Zn, 6 M HCl, EtOAc/EtOH, rt. (a) Li(Et3BH), CH2Cl2, rt then 19

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