The carbohydrate-sesquiterpene interface. directed synthetic routes to both (+)- and (-)-fomannosin from D-glucose.
An enantiodivergent strategy for the total chemical synthesis of both naturally occurring (+)-fomannosin (1) and its (-)-antipode (ent-1) from alpha-D-glucose has been developed and successfully implemented. The key steps in the overall pathway include the following: (i) application of the zirconocene-mediated ring contraction of vinyl furanosides for the construction of highly substituted cyclobutanols; (ii) the use of ring-closing metathesis to form the pendant five-membered ring; (iii) making recourse to a monothio malonic ester to allow for chemoselective reduction to sensitive lactone intermediate 45; (iv) hydroxyl-directed dihydroxylation with OsO(4) to generate 48; and (v) sequential elimination via a cyclic sulfite and a cyclobutyl triflate. The bridge between the enantiomeric series consisted of a six-step linkup involving the structural modification of 22 so as to generate ent-30b. Optical activity was fully preserved throughout.
Paquette
Leo A
LA
Evans Chemical Laboratories, The Ohio State University, Columbus, OH 43210-1185, USA. paquette@chemistry.ohio-state.edu
Peng
Xiaowen
X
Yang
Jiong
J
Kang
Ho-Jung
HJ
D003500:Cyclization; D005947:Glucose / Q000737:chemistry*; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
D007783:Lactones; D012717:Sesquiterpenes; C524830:fomannosin; D005947:Glucose