Formal total syntheses of the (-)-salicylihalamides A and B from D-glucose and L-rhamnose.
[reaction: see text] 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 C13 hydroxyl group had no significant influence on the E:Z ratio during the ring-closing metathesis reaction.
Haack
Torsten
T
Department of Medicinal Chemistry, Center for Cancer Experimental Therapeutics and Center for Drug Discovery, Higuchi Biosciences Center, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045-7582, USA.
Haack
KyoungLang
K
Diederich
Wibke E
WE
Blackman
Burchelle
B
Roy
Subho
S
Pusuluri
Srinivas
S
Georg
Gunda I
GI
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis*; D005947:Glucose; D012210:Rhamnose; D013237:Stereoisomerism
D019086:Bridged Bicyclo Compounds, Heterocyclic; C410986:salicylihalamide A; D005947:Glucose; D012210:Rhamnose