Compounds for preparing immunological adjuvant
The present invention provides methods for preparing TLR-4 receptor agonist E6020: and stereoisomers thereof, which compounds are useful as an immunological adjuvants when co-administered with antigens such as vaccines for bacterial and viral diseases. Also provided are synthetic intermediates.
1. A compound of formula (17):
wherein:
R is hydrogen or a C 1 -C 6 alkyl group;
one of R 2a and R 2b is H and the other is a monovalent nitrogen protecting group, or R 2a and R 2b taken together are a divalent nitrogen protecting group;
R 4 is a C 5 -C 12 alkyl group or a C 5 -C 12 alkenyl group; and
R 5 is a C 5 -C 15 alkyl group or a C 5 -C 15 alkenyl group.
2. A compound of claim 1 , wherein the nitrogen protecting group of R 2a and R 2b is independently selected from the group consisting of Boc, Fmoc, TROC, TMS-ethylcarbonyl, cyanoethylcarbonyl, allyloxycarbonyl, (C 6 H 5 ) 2 C═, tetrachlorophthalamide, or azide.
3. A compound of claim 1 , wherein R is hydrogen; R 2a and R 2b are hydrogen; R 4 is a C 7 alkyl; and R 5 is a C 11 alkyl.
4. A compound of claim 3 , having the formula ER-819120:
5. A compound of claim 1 , wherein R is hydrogen; R 2a and R 2b is a nitrogen protecting group; R 4 is a C 7 alkyl; and R 5 is a C 11 alkyl.
6. A compound of claim 5 , having the formula ER-819302: