Scientist from the Beijing and Tianjin University published recently the enantioselective total synthesis of three diterpenoids which are known as jungermannenones. This 13 step total synthesis is showcasing a rare example of photochemistry in late stage total synthesis by the working group of Prof. Xiaogung Lei.

Late stage photoinduced rearrangement and Schenk-Ene reaction

The work, which was published in Angewandte Chemie, features the total synthesis of (+)-Jungermatrobrunin (2), a diterpenoid which was isolated and reported in 2008 in the Journal of Natural Products. This antifungal compound could be synthesized out of the precursor 1 by a Schenk-Ene reaction. On the same time diacetoxyjungermannenone C (1) rearranged to the natural product 3 which was favored by UV light irradiation.

Synthesis of 9 by stereoselctive 1,4 addition of the starting materials 3 and 4.

Diacetoxyjungermannenone C (1) could be synthesized by the researchers starting from 3 and 4 which were coupled by stereoselective organometallic 1,4-addition using BINOL-based ligand (L). Alpha arylation followed by methylation led to the cis-decalin 6. The following oxidation to 7 was realized under Jones Conditions. All carbonyl groups were reduced in the following step to 8. Tautomerization with Cerchlorid of 7 led to trans-decalin system followed by reduction. Birch reduction finally delivered the ketone 9.

Finalization of the synthesis of 1.

Next, the free alcohols were protected with TMS and alpha functionalization led 10. Reduction and subsequent protection to 11 was followed by reductive cyclization. The terminal alkene was then oxidized to the ketone 12. After protecting group removal and acetylation of the former TMS protected alcohols, alpha methenylation led to the diacetoxyjungermannenone C (1).

This synthesis highlights the fast and effective construction of the tetracyclic core structure of these natural products combined with a interesting light induced skeletal rearrangement.

Published in Angew. Chem. Int. Ed. 2019, 58, 10879. (https://doi.org/10.1002/anie.201903682)