Total Syntheses of 3-epi-Litsenolide D₂ and Lincomolide A

Abstract

The first total syntheses of 3- epi-litsenolide D and its enantiomer lincomolide A were achieved. The synthetic highlights of our approach include olefin cross metathesis and bromine addition to the generated double bond, followed by the regioselective HBr-elimination and intramolecular carbonylation using bis(triphenylphosphine)dicarbonylnickel. This investigation also revealed that the previously reported specific optical rotation of 3- epi-litsenolide D should be revised.

Strain‐Driven Dyotropic Rearrangement: A Unified Ring‐Expansion Approach to α‐Methylene‐γ‐butyrolactones

“…3‐Hydroxyl‐α‐methylene‐γ‐butyrolactone features the core skeleton of a unique family of natural products as represented by licunolide A [32] . We envisioned that this class of natural products could be accessed through dyotropic rearrangement involving C‐O migration.…”

“…Instead, ent ‐licunolide A ( 95 b ) [33] was obtained as major product, apparently through the deprotection of TBS group followed by intramolecular transesterification reaction [13, 34] . Of note, the absolute stereochemistry of 95 b is identical to another natural product 3‐ epi ‐litsenolide D2 [32] …”

Strain‐Driven Dyotropic Rearrangement: A Unified Ring‐Expansion Approach to α‐Methylene‐γ‐butyrolactones

“…3-Hydroxyl-a-methylene-g-butyrolactone features the core skeleton of au nique family of natural products as represented by licunolide A. [32] We envisioned that this class of natural products could be accessed through dyotropic rearrangement involving C-O migration. To test this idea, the chiral a-methylene-b-lactone S94 (for its preparation, see Supporting Information) was examined under the standard conditions.Itturned out that the dyotropic reaction did work.…”

Total Synthesis of 3-<i>epi</i>-Juruenolide C

“…Our synthetic strategy for 1 was initiated using known chiral diol 2, which was derived from a commercially available ethyl sorbate via the Sharpless asymmetric dihydroxylation using 1 mol% of hydroquinine 1,4-phthalazinediyl diether ((DHQ) 2 PHAL) as the chiral ligand [10][11][12] (Chart 1). The enantiomeric purity was estimated as 82% enantiomeric excess (ee) based on its specific optical rotation observed.…”

“…The enantiomeric purity was estimated as 82% enantiomeric excess (ee) based on its specific optical rotation observed. [10][11][12] Next, the diol 2 was transformed to alkene 6 in the following 4 steps: (i) p-methoxybenzyl-(PMB-) protection of 2 using PMB imidate, (ii) diisobutylaluminium hydride (DIBAL-H) reduction of ethyl ester 3, (iii) mesylation of allyl alcohol 4, and (iv) LiAlH 4 reduction of mesylate 5.…”