Synthesis of Eburnane-Type Alkaloids

Key words

(±)-eburnamonine - (±)-larutensine - (±)-melokhanine E - (±)-terengganensine B - Upjohn dihydroxylation - α-iminol rearrangement - aza-Pinacol rearrangement

Significance

Zhu and co-workers present their recent efforts to access eburnane-type alkaloids using a highly divergent approach. The presented route features an α-iminol rearrangement to access the trans-fused core in intermediate D. The conformational bias allowed to close the remaining six-membered ring of the eburnane core in a diastereoselective fashion. The divergent design of the route uses key intermediates D and E to access four different eburnane alkaloids with good yields.

Comment

α-Iminol rearrangement of C led to key intermediate D. Oxidative cleavage of the diol and reduction yielded hexacyclic aminal F as a single dia­stereomer. Lewis acid induced 1,2-alkyl shift of F furnished (±)-terengganensine B. Reduction to alcohol G and Brønsted acid mediated rearrangement allowed synthesis of (±)-larutensine. Oxidation of diol D to the corresponding diketone and subsequent oxidative bond cleavage gave pentacyclic amide I. (±)-Melokhanine E was obtained in five ­additional steps and was then converted into (±)-eburnamonine by means of an aza-pinacol ­rearrangement.