Pipecolic acid biological activity

Further applications of imino dienophiles to the synthesis of natural or biologically active compounds have been directed to (-)-cannabisativine [508] and HIV-1 protease inhibitors [509] Bailey s investigations of the enantioselective synthesis of pipecolic acid derivatives have already been discussed in Sect. 3.1. 

Isoquinuclidines 28 (aza-bicyclo [2.2.2]octanes) consist of IV-bicyclic structures which are the structural element of numerous natural occurring alkaloids with interesting biological properties (Sundberg and Smith 2002). Furthermore, these products can be readily converted to the biologically active pipecolic acids (Krow et al. 1982, 1999 Holmes et al. 1985). A retrosynthetic analysis shows that these isoquinuclidines 28 can be prepared from imines 29 and cyclohexenone 30 (Babu and Perumal 1998 Shi and Xu 2001 Sunden et al. 2005). 

As mentioned above, peptide 153 exists in two or three stable conformational states in solution. However, the proline analog 224 showed only one conformation in various solvents, and extensive NMR experiments revealed that this conformation is very similar to the major conformer of peptide 153. Since analog 224 showed potent cytotoxicity, it is concluded that the major conformation of peptide 153 is at least in part responsible for the activity. The pipecolic acid analog 225 showed similar conformational and biological tendencies. 

---