Tetrahydro- 3-carboline hydantoins

Bonnet and Ganesan [12] developed a new route toward the solid-phase synthesis of tetrahydro-P-carboline hydantoins, which appear in a diverse array of biologically active alkaloids. Due to the presence of tetrahydro-P-carbolines and diketo-piperazine ring skeletons in several bioactive natural products, these two scaffolds became attractive targets for developing a combinatorial chemistry program. 

Figure 15.3 Retrosynthetic analysis of tetrahydro-P-carboline hydantoins.

Figure 15.4 Solid-phase approach to tetrahydro-pi-carboline hydantoins.

Moreover, in the past 10 years, a number of works involving a nucleophilic attack of a nitrogen nucleophile over an acylpalladium intermediate, generated in situ from simple and easily prepared starting compounds, has been reported to be dealing with the synthesis of heterocyclic compounds, that is, 2,3,4,5-tetrahydro-lH-2,4-benzodi-azepine-l,3-dione derivatives 30 [39], tetrahydro-P-carboline/tetrahydriisoquinoline fused 5-lactam derivatives 31 and 32, respectively [40], and substituted hydantoins 33 [41] (Scheme 13.14). 

Sun et al. [52] have developed IL-supported green strategy for the synthesis of oxo- and thio-hydantoin moieties attached with tetrahydro-/3-carboline in aqueous media under microwave irradiation (Scheme 15) [52]. Boc-protected L-tryptophan 124 was anchored on 1 by esterification method to give IL-bound tryptophan 125 (Scheme 15). IL-attached tryptophan 125 tmderwent a Boc deprotection followed by Pictet-Spengler cyclization with... 

SCHEME 15 IL-supported synthesis of hydantoin-fused tetrahydro-/S-carbolines. 

B. Maiti, K. Chanda, C.M. Sun, Traceless synthesis of hydantoin fused tetrahydro-)S-carboline on ionic liquid support in green media, Org. Lett. 11 (2009) 4826-4829. 

---