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

✍ Scribed by Tran Van Loc; Tran Van Sung; C. Kamperdick; G. Adam

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 92 KB
• Volume: 342
• Category: Article
• ISSN: 1615-4150
• DOI: 10.1002/(sici)1521-3897(200001)342:1<63::aid-prac63>3.0.co;2-9

✦ Synopsis

Triterpenes of the betulinic acid type are getting more and more importance because of their interesting pharmacological activities. Especially they display anti-inflammatory [1], antitumor [2], leishmanicidal [3], and antimalarial [4] activities. Most interesting is the fact that betulinic acid, dihydrobetulinic acid, and platanic acid also exhibit anti-HIV activity . Further investigations showed that some amides of betulinic acid are potent HIV inhibitors. The presence of an amide function within the side chain was found to be important for optimal activity. Minor modifications in the lupane backbone strongly affected activity .

3α-Hydroxy-lup-20(29)-ene-23,28-dioic acid (1a) is a rare natural product isolated in surprisingly high yield (7%) from leaves of the Vietnamese plant Schefflera octophylla (Araliaceae) . It is structurally closely related to betulinic acid. Therefore, we have recently synthesized a series of amino acid conjugates of 1a with retainment of the isopropenyl side chain and of the backbone . In continuation of these studies, we now report the synthesis of further derivatives of 1a by oxidation of the isopropenyl side chain, preparation of various mono-and diesters as well as modifications at ring A. Selected derivatives were transformed to amino acid conjugates.