Total synthesis of (+)-macquarimicin A.
The first total synthesis of (+)-macquarimicin A (1), a novel inhibitor of neutral sphingomyelinase (N-SMase) with antiinflammatory activity, has been accomplished. The present work determined the absolute configuration of (+)-1 and revised the C(2)-C(3) geometry to be Z. The synthesis features a transannular Diels-Alder reaction, which constructed the tetracyclic framework stereoselectively, and a convergent and efficient synthetic pathway, which afforded (+)-macquarimicin A (1) in 27 steps (longest linear sequence) with 9.9% overall yield.
Munakata
Ryosuke
R
Department of Applied Chemistry, Keio University, Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
Katakai
Hironori
H
Ueki
Tatsuo
T
Kurosaka
Jun
J
Takao
Ken-ichi
K
Tadano
Kin-ichi
K
D018942:Macrolides / Q000138:chemical synthesis*; D008847:Micromonospora / Q000737:chemistry; D013237:Stereoisomerism
D018942:Macrolides; C094822:macquarimicin A