A non-iterative, flexible, and highly stereoselective synthesis of polydeoxypropionates—synthesis of (+)-vittatalactone

Abstract

A short sequence comprising an oxy-Cope rearrangement, iridium-catalyzed hydrogenation, and enolate methylation provides trideoxypropionates with excellent diastereocontrol. A straightforward synthesis of the cucumber beetle pheromone (+)-vittatalactone illustrates this new strategy.

The use of the lactone motif in chemical communication

“…A chiral auxiliary aldol condensation to form 15 set the stage for a nal auxiliary cleavage and tosyl chloride mediated lactonization to give 9. 11,12 Norvittatalactone 16 was obtained via the same route ( Fig. 3).…”

Strategies for the Synthesis of Deoxypropionates

“…This methodology could also be applied to the total synthesis of (+)-vittatalactone [(+)-7]. 69,70 In a somewhat related approach, Altmann accomplished the total synthesis of the marine cyclodepsipeptide, doliculide (15). 71 The deoxypropionate unit of doliculide (15) was synthesized as shown in Scheme 21.…”

Stereoselective Hydrogenation ofCCBonds: Application to Drug and Natural Product Synthesis

“…353 Acalymma vittatum can be synthesized in a short sequence employing two Ircatalyzed diastereoselective hydrogenations. 354 The latter was converted into corresponding hydroxy ester through transesterification with NaOMe and further converted into iodide 253 (Scheme 29.32). A chemoselective copper-catalyzed alkylation of iodide 253 was performed using i-PrMgCl and catalytic amounts of Li 2 CuCl 4 in the presence of N-methyl-2-pyrrolidinone without affecting the ester moiety, and further reduction with DIBAL-H at À90 C furnished aldehyde 254 in good overall yield.…”

“…Aldehyde 254 was finally converted into (þ)-vittatalactone 255 via reaction sequence: boron aldol reaction/hydrolysis/lactonization. 354 HMG-CoA reductase inhibitors (statins) are a class of drugs that improve blood cholesterol levels by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is responsible for the production of cholesterol in the liver. Statins are widely used medicines in patients with lipid disorders and in the prevention of cardiovascular diseases, 355 and they may also lower the risk of certain cancers 356,357 (e.g., reduce inflammation and hindering cancer growth in prostate tumors).…”