Redox proline derivatives

In these studies the proline-P5C interconversions as central to redox exchange have been emphasized. But hydroxyproline and 3-OH-P5C, the degradative product of hydroxyproline, also may produce regulatory effects, at least theoretically. Since 3-OH-P5C derives only from the degradation of hydroxyproline (1-3), direct effects mediated by their interconversions seem unlikely. However, 3-OH-P5C can interact with the proline - ornithine - glutamate system at several steps (35, 102). Such an interaction is of considerable interest since the intake of hydroxyproline, an animal product, can be nutritionally controlled. Even the endogenous release of hydroxyproline from the breakdown of connective tissue and bone collagen may depend, at least in part, on nutritional factors such as calcium and vitamin D. 

Retrosynthetically, the syntheses of both compounds build on the iridoid 264 as the key intermediate. The required cw-bicyclic skeleton was obtained successfully starting from the (-)-citronellol-derived aldehyde 265. First, an asymmetric enamine-activated a-oxygenation catalyzed by (7 )-proline (70) followed by a Homer-Wadsworth-Emmons (HWE) olefmation gave compound 267. Redox state manipulations and O-protection then result in the formation of the... 

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