PRACTICAL PARTIAL SYNTHESIS OF MYRICERIC ACID-A, AN ENDOTHELIN RECEPTOR ANTAGONIST, FROM OLEANOLIC ACID

Myriceric acid A (1) is an oleanane triterpene that is a potent and sp ecific endothelin A receptor antagonist. A practical procedure for lar ge-scale synthesis of myriceric acid A (1) has been developed starting from oleanolic acid 4. The conversion of oleanolic acid 4 to the key intermediate myricerone 3 was achieved in an efficient manner employin g a photochemical reaction (the Barton reaction) of nitrite 7. Our syn thetic procedure alleviated several difficulties of the original Barto n's procedure with regard to yields and large-scale operation. Myricer one 3 afforded Horner-Wadsworth-Emmons (HWE) type phosphonate 2 which has proved to be a versatile precursor of 1. The preparation of phosph onate 2 on a scale of several hundred grams is described. The synthesi s was completed by condensation of 2 with 3,4-bis[(diphenylmethyl)oxy] benzaldehyde (21), giving alpha,beta-unsaturated ester 22, which was d eprotected to afford 1. The whole synthetic sequence is efficient (14 steps, 31% yield) and requires no chromatographic purification except to obtain the final product 1.