Both stereoisomers of 24-hydroxyvitamin D3, ie, 24 (5’)-hydroxyvitamin D3 and 24 (/?)-hydroxyvitamin D3, stimulate intestinal calcium transport almost equally well in therat. The duration of effect is somewhat shorter for the 24 (S')-hydroxyvitamin D3 than for the 24 (i?)-hydroxyvitamin D3. However, the 24 (5”)-hydroxyvitamin D3 has little or no activity in the mobilization of calcium from bone, in the growth of rats on a low calcium diet, in the ele--^^. lthough it is well established that vitamin D3 must be hydroxylated on C-25 in the liver and subsequently on Cl in the kidney before it can carry out its well-known functions in intestine and bone (DeLuca, 1974), the biological significance of 24-hydroxylation of vitamin D3 metabolites remains unknown. Yet an abundant amount of 24, 25-dihy-droxyvitamin D3 (24, 25-(OH) 2D3)'is found in normal rats (Boyle et al., 1971). Additionally, when 1-hydroxylation of 25-hydroxyvitamin D3 (25-OH-D3) is suppressed, 24-hy-droxylation is stimulated, illustrating that its synthesis is regulated (Boyle et al., 1971, 1972; Omdahl et al., 1972; Holick et al., 1972). The 24, 25-(OH) 2D3 can undergo 1-hydroxylation to form 1, 24, 25-trihydroxyvitamin D3 (l, 24, 25-(OH) 3D3)(Holick et al., 1973), an active metabo-lite on intestinal calcium transport, but so far only trace amounts of this substance have been found in normal ani-mals (Holick et al., 1973; Kleiner-Bossaller and DeLuca, 1974). Thepossibility that 24, 25-(OH) 2D3 is an intermedi-ate in the elimination of vitamin D compounds cannot be excluded, although its persistence in animals would not sup-port this belief (Boyle et al., 1973). There remains, there-fore, the lingering idea that 24-hydroxylation of vitamin D3 t From the Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin—Madison, Madison, Wis-consin 53706, and Laboratory of Chemistry for Natural Products, Tokyo Institute of Technology, Tokyo, Japan. Received February 10. 1975. Supported by a grant from the National Institutes of Flealth (AM-14881), a contract from the Atomic Energy Commission (AT (11-1)-1668), the Food Research Institute of the University of Wisconsin—Madison, and the Ministry of Education of Japan. 1 Abbreviations used are: 24, 25-(OH) 2D3, 24, 25-dihydroxyvitamin D3; 25-OH-D3, 25-hydroxyvitamin D3; l, 24, 25-(OH) 3D3, 1, 24, 25-trihydroxyvitamin D3; 24-OH-D3, 24-hydroxyvitamin D3. vation of serum phosphorus of rachitic rats, or in the calcifi-cation of bone. On the other hand, the 24 (7?)-hydroxyvitamin D3 is almost as active as 25-hydroxyvitamin D3 in all of these systems, although its activity is notalways of equal duration to that of 25-hydroxyvitamin D3. The selectivity of these systems for only one of the 24-hydroxy stereoisomers supports the idea that in vivo 24-hydroxylation of vitamin D compounds is of functional importance. compounds has physiological or functional significance especially since the many functions of the vitamin have not been elucidated.

During the course of our search for a function for this metabolite of vitamin D, the two isomeric forms of 24-hy-droxyvitamin D3 (24-OH-D3) were synthesized, namely 24 (S)-OH-D3 and 24 (7?)-OH-D3 (Ikekawa et al., 1975). In studying their biological activity we were impressed with the marked selectivity for one of these isomers, 24 (/?)-OH-