Macroline synthesis

Liu, X., Cook, J. M. General Approach for the Synthesis of Sarpagine/Macroline Indole Alkaloids. Enantiospecific Total Synthesis of the Indole Alkaloid Trinervine. Org. Lett. 2001, 3,4023-4026. 

The structure for alstonisidine has been revised to (106) on the basis of a possibly biomimetic partial synthesis (Scheme 31) from the two monomeric components, macroline (107) and quebrachamine (108) the latter has now been isolated from the plant source of alstonisidine. 

Villalstonine (109) has been partially synthesized (Scheme 32) from its two halves , pleiocarpamine (110) and macroline, in an analogous synthesis, a process which in this case reverses a degradation of the alkaloid. It is interesting to note that the partial synthesis may well procieed via 11), in which electrophilic attack has occurred at the -position of the pleiocarpamine indole nucleus. As in the example discussed earlier (see p. 211) this / -substitution is secured by a subsequent intramolecular nucleophilic addition to the a-carbon, C-2. 

Synthesis of Sarpagine/Macroline-Related Indole Alkaloids... 

A partial synthesis of villalstonine (322) has been achieved by Cook, following the biomimetic method of LeQuesne (223), by condensation of synthetic (-i-)-macroline (338), or the more stable macroline equivalent (341), with natural pleiocarpamine (342) in ().2N HCl, to furnish villalstonine (Scheme 22). The (+)-macroline was prepared starting from the optically active tetracyclic ketone 343, prepared from D-(-i-)-tryptophan by an en-antiospecific Pictet Spengler reaction and stereocontrolled Dieckmann cyclization. The synthesis (Scheme 23) features the use of a stereoselective Claisen rearrangement, followed by stereospecific hydroboration-oxidation of the exocyclic methylene function at C(16), to install the required C(15) and C(16) stereochemistry (225-227). 

Cook has also carried out a synthesis of 11-methoxymacroline (350), which was then transformed into alstophylline (340), which in view of LeQuesne s previous demonstration of biomimetic alstophylline-macroline coupling to macralstonine (336) (234,235), and Cook s previous synthesis of ( + )-macroline (226,227), constituted a total synthesis of macralstonine (336). Similarly, the synthesis of ( + )-A -methylsarpargine (351) constituted a total synthesis of the bisindole macralstonidine (352), in view of LeQuesne s biomimetic macroline-A -methylsarpagine coupling (236). The synthesis of A -methylsarpagine and 11-methoxymacroline, required preparation of the appropriate methoxytetracyclic ketones 353 and 354 (the methoxysubstituted versions of the tetracyclic ketone 348 used above in the Cook synthesis of (+ )-macroline), which served as versatile templates for elaboration to alstophylline (340) and A -methylsarpagine (351). 

Tran YS, Kwon O (2005) An Application of the Phosphine-Catalyzed [4-1-2] Aimulation in Indole Alkaloid Synthesis Formal Syntheses of (-l-/-)-Alstonerine and (-i-/—)-Macroline. Org Lett 7 4289... 

Wilk, W., Noren-Muller, A., Kaiser, M., and Waldmann, H. (2009) Biology-oriented combined solid- and solution-phase synthesis of a macroline-like compound collection. Chemistry A European Journal, 15, 11976-11984. 

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