Abstract
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.
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This paper is dedicated to Professor Kuniaki Tatsuta with respect and admiration for his achievement of the total syntheses of more than 100 natural products including important antibiotics.
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Sasaki, S., Samejima, S., Uruga, T. et al. Synthetic studies of the spirocyclic cyclohexene part of versipelostatin, a novel GRP78/Bip molecular chaperone downregulator. J Antibiot 66, 147–154 (2013). https://doi.org/10.1038/ja.2012.124
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DOI: https://doi.org/10.1038/ja.2012.124
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