Ring strain and total syntheses of modified macrocycles of the isoplagiochin type

Abstract

SummaryMacrocycles of the bisbibenzyl-type are natural products that are found exclusively in bryophytes (liverworts). The molecular framework of the subtype “isoplagiochin” is of substantial structural interest because of the chirality of the entire molecule, which arises from two biaryl axes in combination with two helical two-carbon units in a cyclic arrangement. From a structural as well as a synthetic point of view we report on the total synthesis of compounds which possess more rigid two-carbon biaryl bridges like stilbene (E or Z) or even tolane moieties which were introduced starting with a Sonogashira protocol. The McMurry method proved to be a powerful tool for the cyclization to these considerably ring-strained macrocycles.

Syntheses of Macrocyclic Bis(bibenzyl) Compounds Derived from Perrottetin E

“…For riccardin C (6) several synthetic routes have been published. [5,25,27,28] We now present a new approach through our improved strategy based on coupling of 20 and the aldehyde 67 as the b-d unit (obtained from the THPprotected iodorarene 66 [38] and the boronic acid 45) and subsequent Wittig macrocyclization (Scheme 13).…”

“…The boronic ester 36 was synthesized from the iodo benzyl alcohol 32 [38] and Suzuki-coupled with the triflate 23. A subsequent Wittig reaction between 37 and 20, hydrogenation and deprotection resulted in compound 39 with a free aldehyde and alcohol function (Scheme 7).…”

“…Riccardin D (11) was obtained by employing an intramolecular Wittig reaction as the key step. The aldehyde 54 (bd unit) was prepared from the boronic acid 53 [38] and the triflate 21 (Scheme 10). For the synthesis of polymorphatin A (12) the "northern" building block 60 containing a protected alcohol and an aldehyde group para to the biaryl axis was required (Scheme 11).…”

Ein Zugang zum enantiomerenreinen axial chiralen Cyclophan Isoplagiochin D durch atrop‐diastereoselektive Heck‐Kupplung

“…Im Falle zweier Methoxy-Substituenten an diesen Positionen wurde die Rotationsbarriere dagegen zu % 66 kJ mol À1 bestimmt, was bei Raumtemperatur im NMR-Spektrum detektierbare Rotamere bedeutet. [7] In jedem Fall verstärkt diese Achse zusammen mit den flexibleren helikalen Elementen an den Ethylenbrücken die Stabilitätauch von Achse a. Die Trennung der beiden Atropisomeren von 1 mittels chiraler HPLC kombiniert mit experimenteller HPLC-CD-Kopplung sowie quantenchemischen CD-Rechnungen [8] erlaubte die Zuordnung der absoluten Konfigurationen.…”

“…Die ste-reoisomere Verteilung von natürlichem 1 variiert abhängig von der Pflanzenquelle und dem Isolierungsprozess. [7] In jedem Fall verstärkt diese Achse zusammen mit den flexibleren helikalen Elementen an den Ethylenbrücken die Stabilitätauch von Achse a. [6] Isoplagiochin D( 1)b esitzt eine hochinteressante chirale Struktur und die Existenz konfigurativ stabiler Atropisomere als Folge axialer Chiralitätk ombiniert mit Ringspannung wurde von uns erstmals im Detail diskutiert.…”