Sinomenine derivatives and processes for their synthesis
View Patent ↗The invention generally provides processes and intermediate compounds useful for the production of sinomenine derivatives. In particular, the process may encompass synthetic routes for the production of (+)-sinomenine derivatives and their intermediates.
1. A compound having a Formula (I):
wherein:
R 1 is selected from the group consisting of hydrocarbyl and substituted hydrocarbyl;
R 2 and R 3 and are independently selected from the group consisting of hydrogen, halogen, OH, NH 2 , CN, hydrocarbyl, and substituted hydrocarbyl;
R 4 is independently selected from the group consisting of halogen, OH, NH 2 , CN, hydrocarbyl, and substituted hydrocarbyl;
R 5 and R 6 are independently selected from the group consisting of hydrogen, OH, NH 2 , SH, hydrocarbyl, and substituted hydrocarbyl, wherein R 5 and R 6 together may form a group selected from the group consisting of ═NOH, ═S, ═CHR 5a , and —O(CH 2 ) 2 O—;
R 5a is selected from the group consisting of hydrogen, halogen, hydrocarbyl, and substituted hydrocarbyl;
R 7 is selected from the group consisting of hydrogen and OR 7a ;
R 7a is selected from the group consisting of hydrocarbyl and substituted hydrocarbyl;
R 8 is selected from the group consisting of hydrogen, hydrocarbyl, and substituted hydrocarbyl;
R 9 and R 10 are independently selected from the group consisting of hydrogen, OH, NH 2 , SH, hydrocarbyl, and substituted hydrocarbyl, wherein R 9 and R 10 together may form a group selected from the group consisting of ═O and ═S;
R 11 and R 12 are independently selected from the group consisting of hydrogen, OH, halogen, hydrocarbyl, and substituted hydrocarbyl;
Y is selected from the group consisting of alkyl, substituted alkyl, carbonyl, and alkyl carbonyl; and,
m is an integer from 0 to 8,
and further wherein C9, C13 and C14 reference carbon numbers 9, 13 and 14, respectively, of Formula (I).
2. The compound of claim 1 , wherein:
R 1 is selected from the group consisting of an alkyl group having from 1 to 8 carbon atoms, a vinyl group, an aryl group, cyclopropyl, cyclobutyl, {—}CH(CF 3 ) 2 , {—}CH(CH 3 )CF 3 , {—}CH═CF 2 , and {—}CH 2 CF 3 ;
R 2 is selected from the group consisting of hydrogen and halogen;
R 4 is OH;
R 5 and R 6 are independently selected from the group consisting of hydrogen, OH, and NH 2 ;
R 3 and R 8 -R 12 are each hydrogen;
Y is selected from the group consisting of {—}CH 2 {—} and {—}CO{—}; and
m is 0.
3. The compound of claim 1 , wherein the compound has a Formula (Ib):
wherein:
R 2 , R 4 , R 5 , R 6 and R 7 are as defined in claim 1 .
4. The compound of claim 1 , wherein the compound has a Formula (Ic):
wherein:
R 2 , R 4 , R 5 and R 6 are as defined in claim 1 .
5. The compound of claim 1 , wherein the compound is selected from the group consisting of:
6. The compound of claim 1 , wherein the optical activity of the compound is (−) or (+) and the configuration of C13, C14, and C9, respectively, is selected from the group consisting of RRS, RSS, SRR, and SSR.
7. A process for preparing a compound of Formula (I) of claim 1 , the process comprising contacting a reactant compound with a compound selected from the group consisting of R 1 YX and R 1 Y to form a the compound of Formula (I) according to the reaction scheme:
wherein:
R 2 and R 3 and are independently selected from the group consisting of hydrogen, halogen, OH, NH 2 , CN, hydrocarbyl, and substituted hydrocarbyl;
R 4 is independently selected from the group consisting of halogen, OH, NH 2 , CN, hydrocarbyl, and substituted hydrocarbyl;
R 5 and R 6 are independently selected from the group consisting of hydrogen, OH, NH 2 , SH, hydrocarbyl, and substituted hydrocarbyl, wherein R 5 and R 6 together may form a group selected from the group consisting of ═NOH, ═S, ═CHR 5a , and —O(CH 2 ) 2 O—;
R 5a is selected from the group consisting of hydrogen, halogen, hydrocarbyl, and substituted hydrocarbyl;
R 1 is selected from the group consisting of hydrocarbyl and substituted hydrocarbyl;
R 9 and R 10 are independently selected from the group consisting of hydrogen, OH, NH 2 , SH, hydrocarbyl, and substituted hydrocarbyl, wherein R 9 and R 10 together may form a group selected from the group consisting of ═O and ═S;
X is halogen;
Y is selected from the group consisting of alkyl, substituted alkyl, carbonyl, and alkyl carbonyl; and
m is an integer from 0 to 8.
8. The process of claim 7 , wherein the reaction is conducted in the presence of an aprotic solvent; the weight ratio of aprotic solvent to compound 3 is from about 1:1 to about 20:1; the weight ratio of the reactant compound to R 1 YX or R 1 Y is from about 1:1.1 to about 1:1.5; the reaction is conducted at a temperature ranging from about 20° C. to about 100° C.; the optical activity of the reactant compound and the compound of formula (I) is (−) or (+), and the configuration of C13, C14, and C9, respectively, is selected from the group consisting of RRS, RSS, SRR, and SSR.