Die Prins‐Makrocyclisierung als effiziente Ringschluss‐Strategie in der Naturstoffsynthese

Abstract

Prins‐Makrocyclisierungen haben sich in jüngster Zeit als gute Methode für die Synthese natürlicher Polyketidderivate bewährt. Diese Reaktion stellt eine ökonomische und selektive Methode zur Bildung Tetrahydropyran‐haltiger Makrocyclen verschiedener Größe zur Verfügung und toleriert vielfältige funktionelle Gruppen im Makrocyclus, in der Regel bei guten bis ausgezeichneten Ausbeuten. Nach der erstmaligen Beschreibung der Prins‐Makrocyclisierung im Jahr 1979 wurde es still um diese Methode; erste Anwendungsbeispiele finden sich erst ab 2008. Der Einsatz dieser Methode in der Naturstoffsynthese hat bei Synthetikern seitdem immer mehr Interesse gefunden, und folgerichtig sind in der jüngeren Literatur zahlreiche Beispiele für Makrocyclisierungen dieses Typs beschrieben worden.

Prins‐Type Cyclization Reactions in Natural Product Synthesis

“…[42] This strategy was reported by the Firmenich group in their synthesis of muscone (Scheme 23). These structures are normally prepared through the formation of the tetrahydropyran followed by closure of the macrocycle.…”

Synthesis of 3‐Oxaterpenoids and Its Application in the Total Synthesis of (±)‐Moluccanic Acid Methyl Ester

“…Herein, we report the preparation of 3-oxaterpenoids and its application in the total synthesis of (AE)-moluccanic acid methyl ester, through a cascade of Prins reaction and polyene cyclization (Scheme 1). [9] We envisaged that a Prins reaction, the classic method to form a THP ring, [10] might serve to initiate the cascade cyclization to provide the anticipated 3-oxaterpenoids. As part of our ongoing efforts to develop intermolecular polyene cyclization, [8] we hypothesized that a modified intermolecular polyene cyclization might furnish 3-oxaterpenoids in a straightforward manner (Scheme 1).…”

“…As part of our ongoing efforts to develop intermolecular polyene cyclization, [8] we hypothesized that a modified intermolecular polyene cyclization might furnish 3-oxaterpenoids in a straightforward manner (Scheme 1). [9] We envisaged that a Prins reaction, the classic method to form a THP ring, [10] might serve to initiate the cascade cyclization to provide the anticipated 3-oxaterpenoids.…”

Total Synthesis of Bryostatin 1: A Short Route

“…[9] In his synthesis, Keck initially set out to prepare the Aring allylsilane 13 (Scheme 1), which was to partner the southern hemisphere enal 29 (Scheme 2) in a novel Lewis acid mediated intermolecular Prins union performed at low temperature (Scheme 3). [10] Kecks route to 13 began with a catalytic asymmetric allylstannation reaction on aldehyde 1 mediated by the complex derived from (S)-binol and titanium tetraisopropoxide (Scheme 1); [11] a reaction that performed in an outstanding manner to install the lone asymmetric centre of 2 (93 % ee). The next key step was the chelation-controlled asymmetric aldol union of aldehyde 3 with the silyl ketene thioacetal 4 that provided alcohol 5 with 41:1 selectivity.…”