Abstract
The use of the intramolecular Nozaki-Hiyama-Kishi reaction to construct 10-membered lactones is described. The influence of the nature of the protecting groups at C4 and C5 on the stereochemistry of the newly formed stereogenic center at C7 was investigated. The utility of this methodology has been demonstrated in the stereoselective total synthesis of (-)-decarestrictine D from 1,3-propanediol and polyhydroxybutyrate (PHB) in 13 steps and 6.3% overall yield.
Highlights
Decarestrictine D (1) is a 10-membered lactone isolated from Penicillium corylophilum, simplicissimum1a-c and independently from the Canadian Tuckahoe fungi Polyporus tuberaster1d and named as tuckolide
A general panel of whole cell screening demonstrated that decarestrictine D inhibits cholesterol biosynthesis in HEPG2 liver cells and this beneficial effect was corroborated by in vivo studies with normolipidemic rats
It appears that decarestrictine D is highly selective in that it exhibits no significant antibacterial, antifungal, antiprotozoal, or antiviral activity
Summary
Decarestrictine D (1) is a 10-membered lactone isolated from Penicillium corylophilum, simplicissimum1a-c and independently from the Canadian Tuckahoe fungi Polyporus tuberaster1d and named as tuckolide. A general panel of whole cell screening demonstrated that decarestrictine D inhibits cholesterol biosynthesis in HEPG2 liver cells and this beneficial effect was corroborated by in vivo studies with normolipidemic rats It appears that decarestrictine D is highly selective in that it exhibits no significant antibacterial, antifungal, antiprotozoal, or antiviral activity. Recent studies[2] revealed DNA-binding activity for decarestrictine D and the corresponding bisglycosylated derivatives, disclosing new avenues of opportunities in structure-activity relationship. Such significant biological properties exhibited by decarestrictine D contributed much to the interest in devising synthetic approaches to this family of natural products. The different local conformations that might be enforced by the protecting groups at C3 and C4 were expected to impart changes on the geometry of the transition state as proposed by Kishi 13 and Schreiber[14]
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