Biomimetic studies on polyenes

Abstract

The crispatenes and SNF4435 C&D are complex polypropionate derived natural products. The core structures of these compounds along with a complex unnatural structure can be easily prepared from a common polyene precursor simply by variation of the reaction conditions. The reaction pathways provide insight into the biosynthesis of these complex natural products.

Asymmetric synthesis of bicyclo[n.1.0]alkanes by the enantioselective 1,3-CH insertion reaction of chiral magnesium carbenoids

“…Thus, the ester group of the product 8 or 9 was reduced with DIBAL-H to an alcohol and then converted to 3,5-dinitrobenzoyl ester 10 with 3,5-dinitrobenzoyl chloride. 9 As shown in Scheme 3, X-ray crystallographic analysis revealed that ester 10 has a (1R,6R)-bicyclo[4.1.0]heptane core structure. 10 From this result, the product of the reaction of 6 with i-PrMgCl was proven to be 9.…”

Total Synthesis of Thuggacin B

“…Treatment of the resulting a,b-unsaturated ketone with ADmix-a [20] followed by TBSOTf/2,6-lutidine gave ketone 8. The aldol reaction between ketone 8 and aldehyde 9 [7] served as a key reaction in the construction of the northern fragment. Two aspects make this step a challenge.…”

“…The vinyl iodide moiety at C11/C12 could be installed by a cross-metathesis strategy. Major fragment 5 was planned to be prepared by the substratecontrolled aldol reaction of aldehyde 9 [7] and ketone 8, which in turn should be generated from benzoic acid 3-oxo-propyl ester 19. [8] Our synthesis commenced with carboxylic acid 6, which was prepared by a standard sequence that involved the known Nagao aldol reaction [9] with acrolein followed by an Evans aldol reaction [10,11] with the intermediate aldehyde (Scheme 2).…”

Totalsynthese von Thuggacin B

“…Die Vinyliodidfunktion an C11,C12 könnte durch einen Kreuzmetatheseansatz entstehen. Das Hauptfragment 5 sollte durch substratkontrollierte Aldolreaktion aus dem Aldehyd 9 [7] und dem Keton 8 generiert werden, das aus Benzoesäure-3-oxopropylester 19 zugänglich sein sollte. [8] Unsere Synthese beginnt mit Carbonsäure 6, die in einer Standardsequenz über die bekannte Nagao-Aldolreaktion [9] mit Acrolein und einer darauf folgenden Aldolreaktion nach Evans [10,11] mit dem intermediär erzeugten Aldehyd hergestellt wurde (Schema 2).…”

“…Durch Reaktion des entstandenen a,b-ungesättigten Ketons mit ADmix-a [20] gefolgt von TBSOTf/2,6-Lutidin wird Keton 8 erhalten. Der Aldolreaktion zwischen Keton 8 und Aldehyd 9 [7] kommt eine Schlüsselrolle im Aufbau des Nordfragments zu. Zwei Aspekte machen dabei diesen Schritt zu einer besonderen Herausforderung.…”