STUDY OF LACTONIZATION PROCESS IN DEOXYCHOLIC-ACID ANALOGS BY MODELING - STRUCTURE OF -ACETOXY-24-NOR-5-BETA-CHOLANO-12-ALPHA,24-LACTONE

The title compound was synthesized from 3 alpha-acetoxy-1 2 alpha-hydr oxy-24-nor-5 beta-cholan-23-oic acid by treating it with dichloroethyl phosphate and triethylamine. The crystals are orthorhombic, space grou p P2(1)2(1)2(1), a = 19.166(2) Angstrom, b = 14.109(2) Angstrom, c = 8 .246(1) Angstrom, V = 2229.9(6) Angstrom(3), Z = 4, D-c = 1.189 g cm(- 3) lambda(CuKalpha) = 1.5418 Angstrom, mu = 0.55 mm(-1), F(000) = 880, T = 298 K. The structure was solved by direct methods and refined to R = 0.049 for 894 observed reflections collected on a CAD-4 diffractom eter. The molecules in the crystal are in their monolactone form. Ener gy calculations, based on molecular modeling were carried out for simi lar molecules containing 6- to 11-membered monolactone and 12- to 22-m embered bislactone rings. The relative minimum energy values, obtained by MMX calculations, show a considerable decrease for monolactone rin gs with less than eight members, and a considerable increase for the b islactones with less than sixteen atoms. The MMX calculations are in a greement with current experimental results which indicate that the mon olactonization occurs only in cases where the number of atoms forming the lactone ring is less than eight.