Total synthesis and structural revision of (+)-uprolide G acetate.
The first, asymmetric total synthesis of the proposed structure of (+)-uprolide G acetate (UGA) is reported, and the spectral properties of the synthetic compound clearly differed from those reported for natural UGA. On the basis of comprehensive analysis of the NMR data, two possible structures for the natural UGA were proposed and their total synthesis achieved, thus leading to the identification and confirmation of the correct structure and absolute configuration of the natural UGA. This synthesis was enabled by development of a novel synthetic strategy, which revolved around three key cyclization reactions: an Achmatowicz rearrangement, Sharpless asymmetric dihydroxylation/lactonization, and ring-closing metathesis. These synthetic studies pave the way for further studies on this class of structurally unusual cytotoxic cembranolides.
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, HK (China).
Liangyu
L
Zhu
Yuan
Y
Liu
Renze
R
Ma
Rongbiao
R
Tong
D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D003500:Cyclization; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D014961:X-Ray Diffraction
D001952:Bridged-Ring Compounds; D007783:Lactones; C416985:uprolide G
macrocycles; natural products; rearrangements; structure elucidation; total synthesis