Total synthesis and biological evaluation of fluorinated cryptophycins

• Christine Weiß,
• Tobias Bogner,
• Benedikt Sammet and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 2060–2066, doi:10.3762/bjoc.8.231

• resulting in macrocyclization according to Moher et al. [34]. In the final steps the dioxolane ring of 21 was cleaved with trifluoroacetic acid in the presence of water. The resulting vicinal diol was not purified, but reacted with a large excess of trimethyl orthoformate. The cyclic orthoester resulting

• 28, representing units A and B was then esterified with 19 under Yamaguchi conditions with 2,4,6-trichlorobenzoylchloride and triethylamine in the presence of catalytic amounts of DMAP. Macrocyclization was brought about by cleavage of the Fmoc protecting group from the unit C amino group, which

• , Amberlyst-15®, rt, 8 d; (h) DIBAL-H, CH2Cl2, −78 °C, 4.5 h; (i) AllylSnBu3, MgBr2∙Et2O, CH2Cl2, −78 °C, 15 h. Assembly of units A–D and macrocyclization, followed by diol-epoxide transformation to give the trifluoromethyl substituted analogue 22 of cryptophycin-52. Reagents and conditions: (a) Grubbs II

A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues

• James R. Cochrane,
• Dong Hee Yoon,
• Christopher S. P. McErlean and
• Katrina A. Jolliffe

Beilstein J. Org. Chem. 2012, 8, 1344–1351, doi:10.3762/bjoc.8.154

• epimers (Scheme 1). While macrocyclization to give the core 2 could be performed at any of the amide or ester bonds [10], we chose to use a macrolactonization approach to enable ready access to analogues of the LI-F04a core through straightforward Fmoc solid-phase peptide synthesis of the linear

• highlighted in yellow. Retrosynthetic strategy. Macrolactonization reactions of seco acids 5 and 6 (for reagents and yields see Table 1 and Table 2). Synthesis of the dehydroxy side chain 12. Synthesis of LI-F04a (1) and analogues 20–23. Reaction conditions for macrocyclization of 5. Reaction conditions for

• macrocyclization of 6. Antifungal activity. Supporting Information Supporting Information File 429: Experimental details for all new compounds. Supporting Information File 430: 1H, 13C and 2D NMR data for all new compounds. Acknowledgements We thank the University of Sydney for financial support and the award of

Synthesis and anion recognition properties of shape-persistent binaphthyl-containing chiral macrocyclic amides

• Marco Caricato,
• Nerea Jordana Leza,
• Claudia Gargiulli,
• Giuseppe Gattuso,
• Daniele Dondi and
• Dario Pasini

Beilstein J. Org. Chem. 2012, 8, 967–976, doi:10.3762/bjoc.8.109

• ][28][29][30], we have reported on the design, synthesis and characterization of a rigid, optically active tetraamidic macrocycle with recognition capabilities towards anions (Figure 1) [31]. In fact, macrocycle (R,R)-1 could be obtained efficiently (62% in the macrocyclization step) through a

• us from pursuing a stepwise methodology for the macrocyclization, which had been used in the case of (R,R)-1 [31]. In order to quickly evaluate the potential of acetyl-protected tetraamidic macrocyles as analogues of (R,R)-1, we proceeded to directly cyclize equimolar amounts of optically pure

Synthesis of multivalent host and guest molecules for the construction of multithreaded diamide pseudorotaxanes

• Nora L. Löw,
• Egor V. Dzyuba,
• Boris Brusilowskij,
• Lena Kaufmann,
• Elisa Franzmann,
• Wolfgang Maison,
• Emily Brandt,
• Daniel Aicher,
• Arno Wiehe and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2012, 8, 234–245, doi:10.3762/bjoc.8.24

• macrocyclization. The use of weak interactions, e.g., metal complexation [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47], charge-transfer interactions [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63], or hydrogen bonding [64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• for the terrestrial cyanobacterium Nostoc sp. ATCC 53789 [55]. The cyclic heptapeptide shares the L-4-methylproline unit of nostopeptolides and is synthesized by two enzymes closely resembling NosE and NosF. A unique feature of nostocyclopeptide biosynthesis is the mechanism of macrocyclization

• libraries of new compounds. Enzymes catalyzing macrocyclization of cyanobactins, as an example, are highly promiscuous and have been successfully used for the cyclization of diverse peptides. Future studies will have to show how many of the fascinating biochemical features of cyanobacterial biosynthetic

Planar-bilayer activities of linear oligoester bolaamphiphiles

• Jonathan K. W. Chui,
• Thomas M. Fyles and
• Horace Luong

Beilstein J. Org. Chem. 2011, 7, 1562–1569, doi:10.3762/bjoc.7.184

• derived alkyl compounds derive from the de-macrocyclization of an earlier active channel [11]. Structurally they similarly consist of a linear topology linked by internal esters (Es); the classes differ by the presence of multiple aromatic rings in the phthalates, and the lack of centrosymmetry in the

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• biologically active compounds are reblastatin (68) and autolytimycin (69). These potent inhibitors of heat shock protein 90, an important therapeutic target for cancer treatment, were accessed by a copper-mediated macrocyclization step of 70 to 71 in high yield (82%, Scheme 16) [67]. The same method was

• some cases, the up to stoichiometric amount of ligand made work-up procedures difficult. In general, CuI is the most efficient catalyst. The reaction conditions are applicable to primary, cyclic secondary aliphatic amines, electron-rich and electron-poor anilines, and heteroarylamines. Macrocyclization

• for the synthesis of promazine drugs. Key intermediate for imatinib. Synthesis of an effective Chek1/KDR kinase inhibitor. Macrocyclization as final step of the synthesis of heat shock protein inhibitor. Synthesis of N-arylimidazoles. Synthesis of benzolactam V8. Synthesis of an intermediate for

The allylic chalcogen effect in olefin metathesis

• Yuya A. Lin and
• Benjamin G. Davis

Beilstein J. Org. Chem. 2010, 6, 1219–1228, doi:10.3762/bjoc.6.140

• . Pertinent examples have also emerged during target syntheses. In the synthesis of palmerolide A analogues by Nicolaou and co-workers, compounds 8a and 9a were found to undergo smooth macrocyclization via RCM, whereas 10a, lacking the allylic hydroxy group, failed to form the desired macrocycle under the

• explanation for favorable macrocyclization by RCM over oligomerization (Scheme 8a). Here, the coordination by the carbonyl oxygen to ruthenium brings the tethered alkene closer in proximity to the alkylidene allowing effective cyclization (Scheme 8b). In a similar manner, the rate enhancement caused by allyl

Templated versus non-templated synthesis of benzo-21-crown-7 and the influence of substituents on its complexing properties

• Wei Jiang and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2010, 6, No. 14, doi:10.3762/bjoc.6.14

• Wei Jiang Christoph A. Schalley Institut für Chemie und Biochemie, Freie Universität Berlin, Takustraße 3, 14195 Berlin, Germany 10.3762/bjoc.6.14 Abstract Two procedures for the synthesis of benzo-21-crown-7 have been explored. The [1+1] macrocyclization with KBF4 as the template was found to be

• more efficient than the intramolecular macrocyclization without template. Pseudorotaxanes form with secondary ammonium ions bearing at least one alkyl chain narrow enough to slip into the crown ether. Substitution on benzo-21-crown-7 or on the secondary ammonium axle alters the binding affinity and

• Discussion Synthesis of C7. Several synthetic procedures for C7 have been explored systematically under phase-transfer conditions by Lukyanenko et al. [28]. Among them, intramolecular macrocyclization via monotosylate 1 generated in situ gives rise to the highest yield (68%). To test the efficiency of

Synthesis and binding studies of two new macrocyclic receptors for the stereoselective recognition of dipeptides

• Ana Maria Castilla,
• M. Morgan Conn and
• Pablo Ballester

Beilstein J. Org. Chem. 2010, 6, No. 5, doi:10.3762/bjoc.6.5

• 4 and trimethylstannyl-aryl 5) to prepare 4,4’-bis(alanyl)benzophenones 3, followed by macrocyclization of two molecular units of 3. The macrocyclization reaction of two 4,4’-bis(alanyl)benzophenones 3 will be promoted by the sequential and regioselective formation of two peptide bonds between them

• macrocyclization reaction. Thus, for the synthesis of antiparallel receptor 1 each benzophenone unit will provide, in an alternative way, one carboxylic and one amino function to the final macrocyclic skeleton. Conversely, for the synthesis of antiparallel receptor 2, one benzophenone unit will donate its two

• carboxylic acid functions while the other will participate with its two amino groups. To achieve the regioselective control demanded in the macrocyclization reactions, a precise selection of the orthogonal protecting groups to be included in the bis-amino acid functionalities of the benzophenone derivatives

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• macrocyclization. Hydrogenation of the olefins followed by saponification of macrolactones 106 and 107 with NaOMe and subsequent MOM protection gave the common intermediate 108 with identical physical data independent of the route used. The lithium enolate formed from 108 with LDA was treated with 109 and the