Spirocycloisomerization of Tethered Alkylidene Glycocyamidines: Synthesis of a Base Template Common to the Palau'amine Family of Alkaloids

Abstract

Die leichte Spirocyclisierung des verbrückten Bisalkylidens 1 lässt auf die Entwicklung einer allgemeine Strategie für die Synthese der Alkaloide der Palau'amin‐Familie hoffen. Die Besonderheiten dieses Modellsystems für die zentrale Einheit werden beschrieben.

Synthetic (±)‐Axinellamines Deficient in Halogen

“…The core of the molecules would derive from a homodimeric precursor, whose oxidative desymmetrization with hypochorite would install the halogenated spirocycle. [9] Notwithstanding the tenuous and challenging prospect of carrying two basic guanidine units intact through the synthesis, this approach was intuitive and direct. For reasons discussed previously [9] , we chose to work with an oroidin synthon at higher oxidation state and targeted a dispacamide dimer (e.g.…”

Quality not Quantity: The Role of Marine Natural Products in Drug Discovery and Reverse Chemical Proteomics

“…Although its acute toxicity is relatively low, palau’amine exhibits powerful antibacterial, antifungal, antitumour and immunosuppressive activities [57]. The complex hexacyclic ring system, dense stereochemistry, high degree of functionalisation and inherent instability of the molecule makes palau’amine a challenging synthetic target [58, 59, 60, 61], and a successful total synthesis has yet to be reported. As is frequently the case with biologically active natural products, the cellular receptors for palau’amine are not known, so palau’amine is an interesting candidate for investigation by reverse chemical proteomics.…”

Challenge Palauamine: Current Standings

“…Scheme 5. Spiro cyclization of alkylidene glycocyamidines (a, Harran et al) [22] and alkylidene hydantoins (b, Hoffmann and Lindel) [23]. There is synthetic work on structures like the DCEF tetracycle 25, e. g. providing compound 40 (Scheme 6).…”

“…Scheme 4. Proposal on the biosynthesis of (-)-palau'amine-type pyrrole-imidazole alkaloids (Harran et al) [22]. Scheme 5.…”

“…Recently, Harran et al put forward an alternative hypothesis on the biogenesis of (-)-palau'amine (3) and related pyrrole-imidazole alkaloids [22]. Two alkylidene glycocyamidine units could form the spirocyclic moiety after electrophilic attack of Cl + .…”