Prostratin and structural or functional analogs thereof
This invention concerns product and process to convert a hydroxyl group (bold in R 3 C—OH) in a tigliane-type compound to a hydrogen (bold in R 3 C—H) to obtain deoxytigliane-type compounds or structural or functional analogs thereof. The process has wide application particularly to produce specific biologically active compounds in quantity for use as pharmaceuticals. In particular the process can be used to convert phorbol to a 12-deoxytigliane (prostratin), which is a therapeutic lead for the treatment of AIDS. New compositions of matter are also disclosed.
1. A compound according to the formula
wherein
R 3 is selected from the group consisting of OR, halo, SeR, SR, SOR, SO 2 R, aryl, NHR, NR 2 , NHCOR, where R is lower alkyl of 1-15 C;
R 4 is selected from the group consisting of hydrogen, alkyl (C1 to C20), cyclic alkyl (C3 to C15) aromatic ring (C4 to C6), hydroxyl, alkyl carbonate, carbamate, ester, ether, thiol, amine, phosphine, phosphate, phosphoramide, phosphoramidite, phosphoramidate, phosphite, phosphonate, sulfate, sulfonate, sulfonamide, sulfone, sulfite, amide, guanidine, and urea; and
R 5 is selected from the group consisting of hydrogen, alkyl (C1 to C20), cyclic alkyl (C3 to C15) aromatic ring (C4 to C6), hydroxyl, alkyl carbonate, carbamate, ester, ether, thiol, amine, phosphine, phosphate, phosphoramide, phosphoramidite, phosphoramidate, phosphite, phosphonate, sulfate, sulfonate, sulfonamide, sulfone, sulfite, amide, guanidine, and urea.
2. The compound as set forth in claim 1 , wherein at least one of R 3 , R 4 , and R 5 have a heteroatom selected from the group consisting of boron, nitrogen, oxygen, phosphorous, sulfur, silicon and selenium.
3. The compound as set forth in claim 1 , wherein R 4 and R 5 are each lower alkyl of 1-15C.
4. The compound as set forth in claim 1 , wherein R 4 and R 5 are each methyl.
5. The compound as set forth in claim 1 , wherein R 4 is selected from the group consisting of OR, OCOR, halo, SeR, SR, SOR, SO 2 R, aryl, NHR, NR 2 , NHCOR, where R is lower alkyl of 1-15 C.
6. The compound as set forth in claim 5 , wherein R 5 is lower alkyl of 1-15C.
7. The compound as set forth in claim 5 , wherein R 5 is methyl.
8. The compound as set forth in claim 1 , wherein R 4 is selected from the group consisting of OR, OCOR, halo, SeR, SR, SOR, SO 2 R, aryl, NHR, NR 2 , NHCOR, where R is lower alkyl of 1-15 C, and
wherein R 3 is selected from the group consisting of OR, halo, SeR, SR, SOR, SO 2 R, aryl, NHR, NR 2 , NHCOR, where R is lower alkyl of 1-15 C.
9. The compound as set forth in claim 8 wherein R 5 is methyl.
10. A pharmaceutical composition comprising a compound according to one of claim 1 - 2 or 3 - 9 .