Patent GB-888420-A (GB)
Title: Reserpine derivatives and their preparation
Filed: 1959-02-10
Abstract: The invention comprises  (1) laevo-rotatory 6a-methyl reserpine and its laevo-rotatory 6b-isomer;  (2) 18 - b  - hydroxy - 11,17a  - dimethoxy - 16b  - methoxycarbonyl - 6a - methyl - 3b ,20a  - yohimbane and its 6b isomer;  (3) the lactone of the two stereoisomeric forms of 16b  - carboxy - 18b  - hydroxy - 11,17a  - dimethoxy - 6 - methyl - 3a ,20a  - yohimbane and their 3b  isomers; (4) the lactones of the two stereoisomeric forms of 16b  - carboxy - 18b  - hydroxy - 11,17a  - dimethoxy - 6 - methyl - D 3 - 20a  - yohimbane;  (5) the two stereoisomeric forms of 18b -acetoxy-11,17a - dimethoxy - 16b  - methoxycarbonyl - 6 - methyl-3a ,20a -yohimbane and their 3b  isomers;  (6) the two stereoisomeric forms of 18b -acetoxy-11,17a  - dimethoxy - 16b  - methoxycarbonyl - 6 - methyl-D 3-20a -yohimbane; and  (7) the preparation of the compounds of (1) above by reacting racemic 2-(61-methoxy-31-indolyl)-1-propylamine with the dextro-rotatory (pyridine) methyl ester of 1b -carboxymethyl-2b -methoxy - carbonyl - 3a  - methoxy - 4b  - acetoxy - 6b -formyl-cyclohexane, treating the resulting mixture of the two stereoisomeric forms of the methyl ester of 18b -acetoxy-11,17a -dimethoxy-16b  - methoxycarbonyl - 6 - methyl - 2,3 - 3,4 - diseco - D 4(21) - 20a  - yohimbene - 3 - carboxylic acid with an alkali metal borohydride in alcoholic solution to get a mixture of the two stereoisomeric forms of 18b -hydroxy-11,17a -dimethoxy-16b  - methoxycarbonyl - 6 - methyl - 3 - oxo - 2,3 - seco - 20a  - yohimbane, acetylating this mixture to yield a mixture of the two stereoisomeric forms of 18b -acetoxy-11,17a -dimethoxy-16b  - methoxycarbonyl - 6 - methyl - 3 - oxo - 2,3 - seco-20a -yohimbane, cyclising one or both of these isomers either separately or in admixture with a dehydrating agent to form one or both of the compounds of (6) above, reducing this material to one or both of the compounds of (5) above, partially saponifying this material to one or both of the compounds of (2) above, which is then trimethoxybenzoylated.  The compounds of (2) above may also be obtained by methanolysis of the compounds of (3) above, which may be obtained by reducing one or both of the compounds of (4) above, and if necessary isomerising any 3a -isomer formed to the 3b -isomer by heating with formic acid.  Compounds of (4) above may be obtained by dehydrating one or both of the stereoisomeric forms of the lactone of 16b  - carboxy - 18b  - hydroxy - 11,17a  - dimethoxy - 6 - methyl - 3 - oxo - 2,3 - seco - 20a  - yohimbane, obtained by lactonising one or both of the stereoisomeric forms of the aforesaid compound, which may be obtained by saponifying one or both of the two isomeric forms of 18b  - acetoxy - 11,17a  - dimethoxy - 16b  - methoxycarbonyl - 6 - methyl - 3 - oxo - 2,3 - seco - 20a -yohimbane, which is obtained by acetylating one or both of the stereochemical forms of 18b  - hydroxy - 11,17a  - dimethoxy - 16b  - methoxycarbonyl - 6 - methyl - 3 - oxo - 2,3 - seco-20a -yohimbane, obtainable from the stereochemical forms p  of the methyl ester of 18b -acetoxy - 11,17a - dimethoxy - 16b  - methoxy-carbonyl - 6 - methyl - 2,3 - 3,4 - diseco - D 4(21)-20a  - yohimbene - 3 - carboxylic acid. Succeeding process stages may be effected on the stereoisomers prepared at each stage either separately or in admixture or on one stereoisomer only. Specifications 868,479 and 887,915 are referred to.