First Total Synthesis of Pandamarine

Abstract

The first total synthesis of pandamarine, an alkaloid isolated from Pandanus amaryllifolius is reported. The key step of this extremely short (six steps in total) and protecting group-free synthesis is a highly efficient cascade reaction sequence initiated by the photooxidation of an easily accessible and symmetric difuran precursor.

Furan Oxidation Reactions in the Total Synthesis of Natural Products

“…The alkaloid pandamarine (74) was similarly synthesized by oxidation of bis[4-(4-methyl-2-furyl)butyl]amine (73a) followed by treatment with ammonia and subsequent acid-induced intramolecular cyclization (Scheme 17). 27 The introduction of a Boc protecting group before the oxidation step allowed the synthesis of pandamarilactone-1 (75), another alkaloid of Pandanus amaryllifolius, as well as pandamarilactonines A-D 76 as a diastereomeric mixture (Scheme 18). 28 Related transformations based on the intermolecular reaction of amines with the primary products of furan oxidation with singlet oxygen were used for the synthesis of (partially) hydrogenated indoles and pyrano[2,3-b]pyrrol-…”

Chemoselective photooxygenations of furans bearing unprotected amines: their use in alkaloid synthesis

“…To our delight when this matter was investigated, the unprotected basic nitrogen functionality did not hinder the desired double photooxidation reaction in the least, but was able to participate later on in the sequence delivering pandamarine 4 just as had been originally envisaged (Scheme 3). 23 Following the success of the pandamarine synthesis, we were driven to further explore the inclusion of unprotected amines in photooxygenation substrates. Our target molecules this time were the ubiquitous pyrrolizidine and indolizidine alkaloids.…”

Straightforward Access to a Great Diversity of Complex Biorelevant γ-Lactams Thanks to a Tunable Cascade Multicomponent Process

“…1 H -Pyrrol-2­(5 H )-ones 1 represent important heterocycles found in many natural products and molecules with a variety of pharmaceutical uses . Several examples possessing interesting structural and biological activities include codinaeopsin ( 2 ), axinellamide ( 3 ), pulchellalactam ( 4 ), pandamarine ( 5 ), and erysotramidine ( 6 ) (Figure ). Among them, 5-hydroxy-1 H -pyrrol-2­(5 H )-ones 7 , also known as γ-hydroxy-γ-lactams, have attracted a lot of interest because of their versatility in organic synthesis and medicinal chemistry .…”