Abstract
Two formal total syntheses of the (-)-salicylihalamides, based on chiral pool approaches, are reported. D-Glucose and L-rhamnose were used to prepare advanced intermediates 23 and 54, which can be converted in three or four steps, respectively, to the target compounds. The synthesis of 23 from a known D-glucose-derivative was accomplished in 12 steps and 17% overall yield, and the synthesis of 54 from a known L-rhamnose-derivative was done in nine steps and 6% overall yield. A key step in the synthesis was a ring-closing metathesis reaction to prepare the macrocyclic ring system. It was demonstrated that the phenolic protecting group was critical for inducing the preferential formation of the desired E isomer. It was further shown that the protecting group at the CIS hydroxyl group had no significant influence on the E:Z ratio during the ring-closing metathesis reaction.
Original language | English (US) |
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Pages (from-to) | 7592-7604 |
Number of pages | 13 |
Journal | Journal of Organic Chemistry |
Volume | 70 |
Issue number | 19 |
DOIs | |
State | Published - Sep 16 2005 |