Total Synthesis of an Atropdiastereomer of RP‐66453 and Determination of Its Absolute Configuration

Abstract

Die absolute Konfiguration des Naturstoffs RP‐66453 (1) wurde durch Totalsynthese seines Atropdiastereomers und spektroskopische Studien beider Verbindungen zu aR, S, S, S, S, S bestimmt. Eine SNAr‐basierte cyclische Etherbildung und eine intramolekulare atropdiastereoselektive Suzuki‐Miyaura‐Kupplung wurden zum Aufbau des schwer zugänglichen bicyclischen A‐B‐O‐C‐Gerüsts von RP‐66453 genutzt.

Isolation, Structure Determination, and Synthesis of Allo‐RA‐V and Neo‐RA‐V, RA‐Series Bicyclic Peptides from Rubia cordifolia L.

“…The [PdA C H T U N G T R E N N U N G (PPh 3 ) 4 ]-catalyzed intramolecular Suzuki-Miyaura coupling reaction of compound 19 efficiently gave cyclodityrosines 20 and 20' in 50 % and 14 % yields, respectively. [24] Although the 1 H, 13 C, and 2D NMR data could not distinguish the structural differences between compounds 20 and www.chemeurj.org 20', owing to line broadening of the signals and their complexity caused by cis/trans isomerization of the tertiary amide bond, we tentatively assigned compounds 20 and 20' to be atropisomers. Although a biphenyl axis usually requires three or four ortho substituents for its conformers to become atropisomers, [25] their 12-membered ring structure and the two bulky benzyloxy groups might provide sufficient steric hindrance to the rotation about the CÀC biphenyl bond.…”

Intramolecular Suzuki–Miyaura Reaction for the Total Synthesis of Signal Peptidase Inhibitors, Arylomycins A2 and B2

“…[36] With the properly functionalized tripeptides 21 and 22 in hand, we set out to examine the desired macrocyclization by intramolecular Suzuki-Miyaura reaction (Table 1). [22,23,37] The inherent need for a base in such cross-coupling reactions poses an epimerization problem. [38] It was assumed that the presence of the unprotected phenol could minimize the epimerization of 21.…”

“…Realizing that these cyclizations were generally low yielding and/or not compatible with peptidic structures, our group has been working on the intramolecular SuzukiMiyaura reaction [22] for macrocycle formation and has accomplished total syntheses of a number of natural products with an endo aryl-aryl bond. [23] Recently, Romesberg et al [5] and our group [24] independently reported total syntheses of arylomycin A 2 (1) with similar strategies. As a continuation of this research program, we became interested in the synthesis of arylomycins B because they display greater antibacterial activity than the A series.…”

Total Synthesis of Complestatin (Chloropeptin II)

“…Considering that the presence of an N-Boc group may lead to a conformation that disfavors the ring closure, we prepared 14 b by coupling of 12 with 13 b (P 1 = H). To our delight, the intramolecular Suzuki-Miyaura reaction [23] cyclophane 15, together with a small amount of partially Odesilylated compound 16, in 66 % yield. The axial chirality of 15 was determined to be aR by detailed NOE studies (see the Supporting Information) as well as from the characteristically upfield shift of the a proton of amino acid F (d = 4.2 ppm).…”