Organic Chemistry Portal
Organic Chemistry Highlights

Monday, December 26, 2022
Douglass F. Taber
University of Delaware

Other Methods for C-C Ring Construction: Melicodenine C(Swierk/Brown), Myrioneurinol (Ma), Pleuromutilin (Pronin), Isorosthin L (Liang), Merrilactone A (Shenvi), Resiniferatoxin (Inoue)

Melicodenine C (4) was isolated from the leaves of Melicope denhamii, a rutaceous shrub found in Borneo that has been used in indigenous medicine. John R. Swierk of Binghamton University and M. Kevin Brown of Indiana University constructed the cyclobutane ring of 4 by photochemical cycloaddition of the pyridone 1 with the alkenyl boronate 2 to give 3 (Angew. Chem. Int. Ed. 2022, 61, e202200725. DOI: 10.1002/anie.202200725).

Myrioneurinol (7), isolated from Myrioneuron nutans, a small tree of north Vietnam, showed significant antimalarial activity. Zhiqiang Ma of the South China University of Technology established the cyclohexenone of 6 by silver-mediated intramolecular [2+2] cycloaddition of the alkyne 5, followed by acid-mediated rearrangement (Angew. Chem. Int. Ed. 2022, 61, e202200085. DOI: 10.1002/anie.202200085).

Pleuromutilin (10) is the parent of a family of potent and commercially-important antibiotics. Sergey V. Pronin of the University of California, Irvine assembled the tricyclic ketone 9 by the radical cyclization of 8 (J. Am. Chem. Soc. 2022, 144, 10174. DOI: 10.1021/jacs.2c04708). Richmond Sarpong of the University of California, Berkeley used a similar strategy in a recent synthesis of longiborneol (not illustrated) (Nature Chem. 2022, 14, 456. DOI: 10.1038/s41557-021-00870-4).

Isorosthin L (13) was isolated from Isodon rosthornii, a perennial herb used to treat rheumatism and sore throats. En route to 13, Guangxin Liang of ShanghaiTech University cyclized the iodoalkene 11 to the pentacyclic 12 (Angew. Chem. Int. Ed. 2022, 61, e202114489. DOI: 10.1002/anie.202114489).

Although some of the Illicium sesquiterpenes promote neurite outgrowth in cortical neuron cell culture, merrilactone A (16) was recently shown to be inactive. Ryan A. Shenvi of Scripps/La Jolla closed the central cyclopentane of 16 by the oxidative cyclization of the thioester 14 to 15 (Angew. Chem. Int. Ed. 2022, 61, e202114514. DOI: 10.1002/anie.202114514).

Resiniferatoxin (19), isolated from the latex of Euphorbia resinifera, has found application as a neuroblocking agent. Masayuki Inoue of the University of Tokyo closed the central cycloheptane of 19 by the decarboxylative radical cyclization of 17 to 18 (Org. Lett. 2022, 24, 929. DOI: 10.1021/acs.orglett.1c04286).

D. F. Taber, Org. Chem. Highlights 2022, December 26.