Synthesis of Amino Acid Conjugates and Further Derivatives of 3α-Hydroxylup-20(29)ene-23,28-dioic acid

Abstract

Triterpenes of betulinic acid type exhibit many interesting biological activities. Therefore a series of new 3α-hydroxy-lup-20(29)-ene-23,28-dioic acid derivatives 2a—22 with putative pharmacological activities were synthesized. As starting compounds 3α-hydroxy-lup-20(29)-ene-23,28-dioic acid (1a), isolated from Schefflera octophylla, or its 3-O-acetyl derivative 1b were used. Mono- and diesters (2a—b from 1a, and 4d from 4c) were prepared with CH2N2. Oxidation of the isopropenyl side chain with OsO4 yielded the 20,29-diols (4a—b from 1b, and 19 from 17), which were in the case of 4b further transformed to the 29-norketones 8a/mdash;b. Oxidation of the isopropenyl side chain with m-chloroperbenzoic acid afforded the 20,29-epoxide 12 (from 1b) and the 29-aldehydes and a-hydroxy aldehydes (13a—c from 2a, 14a—c from 2b, and 16a—c from 15a). Ring A was modified by a tosylation—elimination sequence using p-TsCl/NaOAc, which afforded diolefin 15a (from 2a) with Δ2,20(29) double bonds or 23-nor-Δ3,20(29)diolefin 17 (from 1a). Compounds 4b, 4c, and 8a were coupled with L-methionin, L-phenylalanin, L-alanin, L-serin, and L-glutaminic acid via amide bonds at positions 23 and 28 to afford the amino acid conjugates 5a—7b and 9a—11.