Synthesis of enantiomerically pure mimulaxanthin and of its (9Z,9′Z)- and (15Z)-isomers

Article abstract of DOI:10.1002/hlca.19910740303

We present the details of a synthesis of optically active, enantiomerically pure stereoisomers of mimulaxanthin ( = (3S,5R,6R,3′S,5′R, 6′R)-6,7,6′,7′-tetradehydro-5,6,5′,6′-tetrahydro- β,β-carotin-3,5,3′,5′-tetrol) either as free alcohols 1a and 24a or as their crystalline (t-Bu)Me₂Si ethers 1b and 24b. Grasshopper ketone 2a, a presumed synthon, unexpectedly showed a very sluggish reaction with Wittig-Horner reagents. Upon heating with the ylide of ester phosphonates, an addition across the allenic bond occurred. On the contrary, a slow but normal 1,2-addition took place with the ylide from (cyanomethyl) phosphonate but, unexpectedly, with concomitant inversion at the chiral axis. So a mixture of (6R,6S,9E,9Z)-isomers 69 was produced (Scheme I ). However, a fast and very clean 1,2-addition occurred with the ethynyl ketone 12 to yield the esters 13 and 14 (Scheme 2). DlBAH reduction of the separated stereoisomers gave the allenic alcohols 15 and 16 in high yield. Mild oxidation to the aldehydes 17 and 18 followed by their condensation with the acetylenic C ₁₀-bis-ylide 19 led to the stereoisomeric 15,15′- didehydromimulaxanthins 20 and 22, respectively (Schemes 3 and 4). Mimulaxanthins 1 and 24 were prepared by partial hydrogenation of 20 and 22 followed by a thermal (Z/E)-isomerization. As expected, the mimulaxanthins exhibit very weak CD curves, obviously caused by the allenic bond that insulates the chiral centers in the end group from the chromophor. On the contrary , some of the C₁₅-allenic synthons showed not only fairly strong CD effects but also a split CD curve which, in our interpretation, results from an exciton coupling between the allene and the C(9)=C(10) bond. We postulate a rotation around the C(8)-C(9) bond, presumably caused by an intramolecular H-bond in 16 or by a dipol interaction between the polarized double bonds in 6, 7,8, and 17.