Synthetic studies of the spirocyclic cyclohexene part of versipelostatin, a novel GRP78/Bip molecular chaperone downregulator.
The spirocyclic part consisting of an α-acylated tetronic acid and a multisubstituted cyclohexene embedded in versipelostatin, a novel GRP78/Bip molecular chaperone downregulator, has been synthesized in enantiomerically pure form. The asymmetric synthesis of the targeted spiro[4.5]-1-oxa-7-decen-2,4-dione derivative was characterized by (1) stereoselective allylation at the α-carbon of methylmalonate diester, in which one carboxylic acid was esterified with a D-glucose-derived chiral template, (2) construction of the tetrasubstituted cyclohexenone substructure by high-yielding ring-closing metathesis and (3) stereoselective construction of the spirocyclic tetronic acid part starting from the cyclohexenone obtained as the ring-closing metathesis product.
Department of Applied Chemistry, Keio University, Yokohama, Japan.
Shu
S
Sasaki
Suguru
S
Samejima
Tomoki
T
Uruga
Kai
K
Anzai
Natsumi
N
Nishi
Eriko
E
Kawakita
Ken-ichi
K
Takao
Kin-ichi
K
Tadano
D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000737:chemistry; D015536:Down-Regulation / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D003510:Cyclohexanes; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018942:Macrolides; D009844:Oligosaccharides; D013141:Spiro Compounds; C490154:versipelostatin