Lundurines

This ring system is present in some indole alkaloids such as deoxyisoaustamide [10-12], okarimine N [13, 14], balasubramide [15, 16], lundurines [17, 18], apparericine [19], and ervaticine (or conolidine) (Fig. 4.3) [20, 21]. 

Traditionally, synthetic approaches toward this framework were charactoized by a lack of generality, involving poorly available starting material that require multistep synthetic transformations [22-25]. More recent approaches include tandem cleavage of hydrogenated / -and a-carbolines [26], ring closing metathesis [27], and metal-catalyzed Friedel-Crafts-type reactions of indole derivatives with several electrophiles (such as alkynes, alkenes or epoxides) (see Refs. [118] and [133] in Chap. 1 [28-32]). 

Lundurines A-D [17, 18] are a new type of indole alkaloids characterized by the presence of a cyclopropyl moiety embedded within a hexacyclic ring system that includes a l//-azocine[5,4-h]indole ring unit (Fig. 4.4). 

These novel dihydroindole derivatives have been isolated from plants of the genus Kopsia, and have proven to be rich sources of novel alkaloids with intriguing carbon skeletons that display a wide variety of interesting activities.  

In Fig. 4.5, other examples of indole alkaloids isolated from the genus Kopsia are depicted [36, 39—41]. In particular, the indoloazocine derivative lapideilectine B has been synthetized by Pearson and coworkers in 23 linear steps [42, 43]. 

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The molecular formula of tenuisine A (316), C44H41N4O10 was established by HRFABMS. The UV spectrum was that of a dihydroindole and somewhat reminiscent of that of lundurine B (282). The NMR spectral data showed the presence of an aromatic methoxy group at C(10), a carbamate function, an oxygenated quaternary carbon attributable to C(7), a lactone carbonyl... 

The major alkaloids of K. tenuis are lundurines A-C (220-222), which contain a novel ring system incorporating a cyclopropyl unit. These alkaloids are obviously closely related biogenetically to the lapidilectines and may well be derived from an intermediate such as lO-methoxy-3-oxolapidilectine B 181). 

Didehydroervatamine, in E-10191 Ervincine, in P-10116 16j5-Hydroxy-19/ -vindolinine, in V-10024 16jff-Hydroxy-195-vindolinine, in V-10024 Lundurine B, in L-30059 3-Oxovincadifformine, in V-10022 5-Oxovincadifformine, in V-10022 Rhazimol, in A-10036 195-Vindolinine A-oxide, in V-10024... 

The main tetracyclic core of these alkaloids has been synthesized via %-endo-dig cyclization of alkynyl indole catalyzed by AuCls, which affords exclusively the desired azocine[5,4—hjindole derivative (Scheme 1.41) [239]. Thus, based on previously reported results, our objective was to develop an efficient approach toward the total synthesis of lundurines. 

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