Formal total synthesis of (+)-salicylihalamides A and B: a combined chiral pool and RCM strategy.
The formal total synthesis of the (+)-salicylihalamides A and B is detailed, utilizing a chiral pool approach to generate the three stereogenic centers and a ring-closing metathesis (RCM) for the formation of the macrocyclic ring structure. Starting from a known glucose-derived alcohol, the formal total synthesis was achieved in an efficient 13-step protocol in 26% overall yield. It was found that substitution at the remote phenolic group significantly influenced the ratio of the E- and Z-double bond products in the RCM step. The introduction of phenol protecting groups provided E-isomers preferentially and also enhanced the rates of the RCM reactions.
Yang
KyoungLang
K
Department of Medicinal Chemistry, Center for Cancer Experimental Therapeutics, and the Drug Discovery Program, Higuchi Biosciences Center, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045-7582, USA.
Blackman
Burchelle
B
Diederich
Wibke
W
Flaherty
Patrick T
PT
Mossman
Craig J
CJ
Roy
Subho
S
Ahn
Yu Mi
YM
Georg
Gunda I
GI
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis*; D002384:Catalysis; D003500:Cyclization; D009941:Organomercury Compounds / Q000737:chemistry; D010636:Phenols / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry; D013237:Stereoisomerism
D019086:Bridged Bicyclo Compounds, Heterocyclic; D009941:Organomercury Compounds; D010636:Phenols; C410986:salicylihalamide A; D012428:Ruthenium