Organic Chemistry Portal
Organic Chemistry Highlights

Monday, December 24, 2018
Douglass F. Taber
University of Delaware

Diels-Alder Cycloaddition: Maoecrystal P (Luo), Sculponin R (Dong), Jerantinine C (Jiang), Phomoidride D (Wood), Azitine (Ma), Sarcophytin (Carreira)

The diterpene maoecrystal P (4), isolated from the Chinese medicinal plant Isodon eriocalyx, shows significant cytotoxic activity. A key step in the synthesis of 4 described by Tuoping Luo of Peking University was the assembly of 3 by the Diels-Alder cycloaddition of the dienophile 2 to the diene 1 (Angew. Chem. Int. Ed. 2018, 57, 760. DOI: 10.1002/anie.201711084).

The diterpene sculponin R (8) was also isolated from Isodon. The route to 8 devised by Guangbin Dong of the University of Chicago began with the diastereoselective addition of 5 to the diene 6 (Angew. Chem. Int. Ed. 2018, 57, 6333. DOI: 10.1002/anie.201803709).

Jeantinine C (12), isolated from Tabernaemontana corymbosa, also shows significant cytotoxic activity. Xuefeng Jiang of East China Normal University established a versatile route to the oxygenated aspidospermine alkaloids, including 12, starting with the addition of 10 to 9 to give 11 (Org. Lett. 2018, 20, 292. DOI: 10.1021/acs.orglett.7b03694).

John L. Wood of Baylor University assembled the triene 13. Oxidation led to the cyclohexadienone, that cyclized spontaneously to 14, with many of the elements of phomoidride B (15) already in place (Angew. Chem. Int. Ed. 2018, 57, 1991. DOI: 10.1002/anie.201712369).

Dawei Ma of the Shanghai Institute of Organic Chemistry used a similar oxidation/cyclization sequence to convert 16 to 17. All that remained to complete the synthesis of azitine (18) was the construction of the last cyclic quaternary center (Angew. Chem. Int. Ed. 2018, 57, 6676. DOI: 10.1002/anie.201803018).

Erick M. Carreira of ETH Zurich envisioned the assembly of sarcophytin (21) by the cyclization of 19 to 20. Hypothetically, either geometric isomer of either diastereomer of 19 could have been useful, but in practice only the cyclization illustrated was successful (Angew. Chem. Int. Ed. 2018, 57, 823. DOI: 10.1002/anie.201711372).

D. F. Taber, Org. Chem. Highlights 2018, December 24.