Concise asymmetric synthesis of (R)-(+)-tanikolide

A highly stereoselective total synthesis of (R)-(+)-tanikolide, a δ-lactonic marine natural product, was accomplished in seven steps from easily available starting materials with a 51% overall yield. An asymmetric synthesis of an α-hydroxy aldehyde having a stereogenic quaternary center, by the use of (S)-2-(anilinomethyl)pyrrolidine as a chiral auxiliary, was employed in a key step.

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(2R,5S)-2-Dodecanoyl-3-phenyl-1,3-diazabicyclo-[3,3,0]-octaneC24H38N2O[α]D23=−29.3(c1.0,CHCl3)Absolute configuration: (2R,5S)

Methyl (R)-4-formyl-4-hydroxyhexadecanoateC18H34O4[α]D24=+5.9(c1.0,CHCl3)Absolute configuration: (R)

Methyl (R)-4-hydroxy-4-hydroxymethylhexadecanoateC18H36O4[α]D24=−1.1(c1.0,CHCl3)Absolute configuration: (R)

Methyl (R)-5-tert-butyldiphenylsiloxymethyl-5-hydroxyhexadecanoateC34H54O4SiEe >99%[α]D28=−2.7(c0.25,CHCl3)Absolute configuration: (R)

(R)-4-Hydroxy-4-hydroxymethylhexadecanoic acidC17H34O4[α]D27= −0.8 (c 1.0, CHCl3)Absolute configuration: (R)

(+)-TanikolideC17H32O3Ee >99%[α]D23= +2.85 (c 0.65, CHCl3)Absolute configuration: (R)