X-ray crystal structure of the tert-octylamine salt (RMS-431) of pravastatin.

In the course of studies to detect specific inhibitors of cholesterol synthesis from microbial products, several compounds were isolated from the culture broth of Penicillium dtrinum.^ One compound, sodium (+)-(3i?,5i?)-3,5-dihydroxy7-[(l S,2S,6S,8£,8ai?)-6-hydroxy-2-methyl8 [(£)2-methylbutyryloxy] 1 , 2, 6, 7, 8, 8a-hexahydro1naphthyl]heptanoate (CS-514) (la, pravastatin sodium) found as a minor urinary metabolite of ML-236B (Ib) in dogs was especially significant on account potency, tissue selectivity and low toxicity.2) la was also obtained by microbiral transformation of ML-236B.3) The structures of Ib (ML-236B)/ Ic (monakolin K),4) and Id (RMS-414)5) have already been studied by Xray analyses. Similar results for Ib and Ic, designated as compactin and mevinolin, were also reproted by Brown et al.96) and Alberts et aLp respectively. The aim of the present investigation was to establish the stereochemical configuration of CS-514, especially of the asymmetric carbon at the 5 position. Despite many attempts at crystallization of CS-514 as the sodium salt, a single crystal suitable for X-ray analysis could not be obtained. Thus, we decided to use for the analysis the ter/-octylamine salt (RMS-431) of CS-514, in which the sodium has been replaced by the organic amine cation. RMS-431 was prepared by means of the following procedure :