Chiral indoline alkaloid

This method was successfully applied to the total synthesis of chiral indoline alkaloid 2Sh, which is Wierenga s synthetic intermediate for the left hand segment of the antitumor agent ( + ) CC 1065. As shown in Scheme 10.28, the asymmetric hydrogenation of N methanesulfonyl indole (24g) to the corresponding indoline (25g) with 93% ee was the key step. 

Enantioenriched indolines are very important compounds, which exist extensively in natural alkaloids or unnatural bioactive compounds. The development of facile methods toward chiral indolines continues to be a challenge for organic chemists. Unprotected indole 106 could be considered as a special enamine in an aromatic system. Inspired by the possible shift between enamine and imine of indole in the presence of strong acid. Sun and Chen et al. envisioned that a direct reduction of indole 106 to indoline 107 by a combined catalysis of Lewis base and Br0nsted acid would be highly possible (Scheme 32.24). Indeed, using the strategy... 

In 2005, Ary a and co-workers reported on the stereocon-trolled solid-phase synthesis of a 90-membered library of indoline-alkaloid-like polycycles 41 and 42." These compounds are structurally related to a number of alkaloids such as vindoline, tabersonine, and yohimbine, and they could lead to compounds with similar or improved biological properties. Thus, chiral aminoindoline 36 was loaded via a silyl linker unit 37, deprotected, and reacted with an acid chloride to introduce the first point of diversity and to give 38. Treatment with piperidine removed the Fmoc group, and concomitant cyclization provided tricyclic... 

Chiral butyrolactones of type 27 and 28 have substantial value in asymmetric synthesis because they contain readily differentiable difunctional group relationships e.g. 1,5-di-carboxylic acid, 1,4-hydroxy carboxylic acid, 1,6-hydroxy-carboxylic acid, 1,6-diol etc.) that would be difficult to assemble by existing asymmetric condensation and pericyclic processes. Applications of these chiral derivatives of glutaric acid to syntheses of indole, indoline and quinolinone alkaloids are illustrated in Schemes 16-18. 

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