BIOMONITORED SYNTHESIS ROUTE FOR LARGE SCALE PREPARATION OF CARDOL (BILOBOL) AND 11?-CARDOL

摘要

The present report is about a "biomonitored synthesis route for large scale preparation of cardol (bilobol) and SUP11/SUP?-cardol" in 15 steps. The 10 first steps are related to the production of Cardol, starting from 3,5-dimethoxy benzoic acid, and having the following intermediates 3,5-dimethoxybenzoyl chloride (1), 2-(3,5-Dimethoxy­benzoyl)-cyclohexanone (2), 7-(3,5- Dimethoxy-phenyl)-7-oxo-heptanoic acid (3), 7-(3,5-Dimethoxy-phenyl)-heptanoic acid (4), 7-(3,5- Dimethoxy­phenyl)-heptanoic acid ethyl ester (5), 7-(3,5-Dimethoxy-phenyl)-heptan-1-ol (6), 1-(7-lodo-heptyl )-3,5-dimethoxy-benzene (7), 1,3-Dimethoxy-5­pentadec-8-ynyl-benzene (8), 1 ,3-Dimethoxy-5-((Z)-pentadec-8-enyl )­benzene (9), up to the target product ((Z)-5-Pentadec-8-enyl)-benzene-1,3 diol or Cardol (10). In relation to the production ofSUP11/SUP?-Cardol, it is started from the 1-(7-Iodo-heptyl)-3,5-dimethoxy-bénzene (7), by introducing specifically in this sequence the intermediates 10-(3,5-Dimethoxy-phenyl)-dec-2-yn-1-ol (11), 1 -(1 0-Iodo-dec-8-ynyl )-3,5-dimethoxy-benzene (12), 1,3-Dimethoxy-5­pentadeca-8,11-diynyl-benzene (13), 1,3-Dimethoxy-5-((8Z,I1Z)-pentadeca­8,11-dienyl)-benzene (14) and the target product ((8Z,11Z)-5-Pentadeca-8,11­dienyl)-benzene-1,3-diol (15) or SUP11/SUP?--cardol. All the intermediates and the target product had their obtaining methods generated in the concept of results optimization.