Patent GB-868475-A (GB)
Title: Improvements in or relating to reserpine and its derivatives
Filed: 1957-10-30
Abstract: The invention comprises laevo-rotatory and dextro-rotatory 18b -acetoxy-11, 17a -dimethoxy3-oxo-16b -methoxy carbonyl-2,3-seco-20a -yohimbane, (A), dextralaevo and racemic 18b -hydroxy-11, 17a -dimethoxy-3-oxo-16b -carboxy -2,3-seco-20a -yohimbane, their corresponding lactones, the lactone of 18b -hydroxy-11,17a -dimethoxy-16b -carboxy-3, 4-dehydro- 20a -yohimbane chloride (B), and a process for the production of reserpine which comprises lactonising dextro- 5b -hydroxy-8-oxo-, 1, 4, 4aa , 5, 8, 8aa hexahydronaphthalene-1b -carboxylic acid, reducing the resulting laevo lactone of 5b -hydroxy-8-oxo-1, 4, 4aa , 5, 8, 8aa -hexahydronaphthalene-1b -carboxylic acid to the 1,8-lactone of laevo-5b ,8b -dihydroxy-1, 4, 4aa , 5, 8, 8aa -hexahydronaphthalene-1b -carboxylic acid, reacting this with an N-bromoimide, N-bromoamide or N-bromo hydantoin to obtain the dextro lactone of 8b -hydroxy-2a -bromo-3b ,5b -epoxy-1, 2, 3, 4, 4aa , 5, 8, 8aa -octahydronaphthalene-1b -carboxylic acid, methoxylating the said dextro lactone in the 2a -position, brominating the methoxy lactone in the 6a -position with an N-bromoimide, bromoamide or bromo-hydantion to give the laevo 1,8-lactone of 6a -bromo-7b ,8b -dihydroxy-2a -methoxy- 3b ,5b -epoxy-4aa , 8aa -decahydronaphthalene-1b -carboxylic acid, oxidising it to give the laevo lactone of 6a -bromo-8b -hydroxy-2a -methoxy-3b , 5b -epoxy-7-oxo-4aa , 8aa -decahydronaphthalene-1b -carboxylic acid, reducing it to laevo-3b -hydroxy-2a -methoxy-7-oxo-1, 2, 3, 4, 4aa , 7, 8, 8aa -octahydronaphthalene-1b -carboxylic acid, p  esterifying to produce the laevo methyl ester of 3b -hydroxy-2a -methoxy7-oxo-1, 2, 3, 4, 4aa , 7, 8, 8aa -octahydronaphthalene-1b -carboxylic acid, acetylating the 3b -hydroxy group, ozonising the product to 1b -carboxymethyl-2b -methoxycarbonyl-3a -methoxy-4b -acetoxy-6b -formyl cyclohexane, methylating it to the laevo-methyl ester, condensing the latter with 6-methoxytryptamine, reducing, cyclising and hydrolysing the product to dextro18b -hydroxy-11,17a -dimethoxy-3-oxo-16b - carboxy-2, 3-seco-20a -yohimbane, lactonising it and then cyclising the resulting lactone (C), to the lactone of 18b -hydroxy-11,17a -dimethoxy-16b -carboxy-3, 4-dehydro-20a -yohimbane, reducing the latter to reserpic acid lactone, converting this to methyl reserpate and esterifying with a 3, 4, 5-trimethoxy benzoylating agent to give reserpine; also a process for the preparation of dextro-A by condensing the laevo methyl ester of 1b -carboxymethyl-2b -methoxy-carbonyl-3a -methoxy-4b -acetoxy-6b -formyl cyclohexane with 6-methoxy tryptamine, treating the product with sodium borohydride and then acetylating with acetic anhydride and pyridine; a process for preparing dextro C by lactonising laevo 18b -hydroxy-11, 17a -dimethoxy-3-oxo-16b -carboxy-2,3-seco-20a -yohimbane with acetic anhydride in the presence of acetic acid and lithium acetate, and also a process for preparing B by cyclising the laevo lactone C with phosphorus oxychloride.  Detailed examples illustrate the synthesis.  Specifications 799,271, 868,483, 868,484, 868,485 and 868,486 are referred to.