Aza-Diels-Alder reactions (ADARs) are powerful processes that furnish N-heterocycles in a straightforward fashion. Intramolecular variants offer the additional possibility of generating bi- and polycyclic systems with high stereoselectivity. We report herein a novel Brønsted acid catalyzed process in which ortho-quinone methide imines tethered to the dienophile via the N substituent react in an intramolecular ADAR to form complex quinolizidines and oxazinoquinolines in a one-step process. The reactions proceed under very mild conditions, with very good yields and good to very good diastereo- and enantioselectivities. Furthermore, the process was extended to a domino reaction that efficiently combines substrate synthesis, ortho-quinone methide imine formation, and ADAR.
The efrapeptin family of peptide antibiotics produced by the fungus Tolypocladium niveum, and the neo-efrapeptins from the fungus Geotrichum candidumare inhibitors of F(1)-ATPase with promising antitumor, antimalaria, and insecticidal activity. They are rich in C(α)-dialkyl amino acids (Aib, Iva, Acc) and contain one β-alanine and several pipecolic acid residues. The C-terminus bears an unusual heterocyclic cationic cap. The efrapeptins C-G and three analogues of efrapeptin C were synthesized using α-azido carboxylic acids as masked amino acid derivatives. All compounds display inhibitory activity toward F(1)-ATPase. The conformation in solution of the peptides was investigated with electronic CD spectroscopy, FT-IR spectroscopy, and VCD spectroscopy. All efrapeptins and most efrapeptin analogues were shown to adopt helical conformations in solution. In the case of efrapeptin C, VCD spectra proved that a 3(10)-helix prevails. In addition, efrapeptin C was conformationally studied in detail with NMR and molecular modeling. Besides NOE distance restraints, residual dipolar couplings (RDC) observed upon partial alignment with stretched PDMS gels were used for the conformational analysis and confirmed the 3(10)-helical conformation.
Aza-Diels-Alder-Reaktionen (ADARs) sind leistungsfähige Prozesse zum schnellenu nd stereoselektiven Aufbau von Stickstoffheterocyclen. Intramolekulare Varianten bieten darüber hinaus die Mçglichkeit, bi-und polycyclische Ringsysteme in einem Schritt mit hoher Stereoselektivitätz u generieren. In dem hier entwickelten Brønsted-Säure-katalysierten Verfahren kçnnen nun erstmals ortho-Chinonmethidimine,d ie über den Iminsubstituenten an ein Dienophil gebunden sind, in einer enantioselektiven ADAR mit inversem Elektronenbedarf zu komplexen Chinolizidin-und Oxazinochinolin-Ringsystemen umgesetzt werden. Die Reaktionen laufen unter milden Bedingungen in sehr guten Ausbeuten und mit guten bis sehr guten Diastereo-und Enantioselektivitäten ab.D as Verfahren kann darüber hinaus zu einem Domino-Prozess erweitert werden, der Substratsynthese,o rtho-Chinonmethid-Bildung und ADAR effizient vereinigt.
A new enantiopure heteroscorpionate ligand HOPhbpm 3menth (2) was synthesized in a one-pot synthesis. Ligand 2 was obtained in a pyridine-catalysed Peterson rearrangement starting from menthopyrazole, thionyl chloride, and salicylaldehyde. The evi-
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