Synthesis of amino acid conjugates and further derivatives of 3 alpha-hydroxylup-20(29)ene-23,28-dioic acid

Triterpenes of betulinic acid type exhibit many interesting biological acti vities. Therefore a series of new 3 alpha-hydroxy-lup-20(29)-ene-23,28-dioi c acid derivatives 2a - 22 with putative pharmacological activities were sy nthesized. As starting compounds 3 alpha-hydroxy-lup-20(29)-ene-23,28-dioic acid (1a), isolated from Schefflera octophylla, or its 3-O-acetyl derivati ve 1b were used. Mono- and diesters (2a-b from 1a, and 4d from 4c) were pre pared 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-b. Oxidation of the isoprope nyl side chain with m-chloro-perbenzoic acid afforded the 20,29-epoxide 12 (from 1b) and the 29-aldehydes and alpha-hydroxy aldehydes (13a -c from 2a, 14a-c from 2b, and 16a-c from 15a). Ring A was modified by a tosylation-el imination sequence using p-TsCl/NaOAc, which afforded diolefin 15a (from 2a ) with Delta(2,20(29)) double bonds or 23-nor-Delta(3,20(29))diolefin 17 (f rom 1a). Compounds 4b, 4c, and 8a were coupled with L-methionin, L-phenylal anin, 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.