SYNTHESIS OF ISOTOPICALLY LABELED CAROTENOIDS - INVESTIGATIONS ON STRUCTURE AND FUNCTION OF CAROTENOPROTEINS AT THE ATOMIC-LEVEL

A three-part strategy has been developed to study molecular interactions in biological systems. Isotopically labelled carotenoids or other substances are prepared by organic total synthesis in specific isotopically labelled form. These small molecules are used to assemble the active biological system, which is then studied by physical techniques. A general synthetic scheme for the synthesis of carotenoids, both symmetrical and asymmetrical, selectively labelled with C-13 at predetermined positions in the C-10-central part, is presented. The synthetic scheme is based on the C-15 + C-10 + C-15 strategy. For symmetrical carotenoids the C-10-dialdehyde, 2,7-dimethylocta-2,4,6-triene-1,8-dial 1, is used. For asymmetrical carotenoids two novel synthons are introduced: 2,7-dimethylocta-2,4,6-triene-8-alnitrile 2 and N-methoxy-N,2,7-trimethylocta-2,4,6-triene-8-alamide 3. The use of these synthons is illustrated by the synthesis of labelled beta-carotene 4, astaxanthin 5 and spheroidene 6. Some of the structural and functional results that have been obtained by this strategy in the fields of photosynthesis and vision, are given.