Asymmetric total syntheses of (-)-jorumycin, (-)-renieramycin G, 3-epi-jorumycin, and 3-epi-renieramycin G.
The total synthesis of (-)-jorumycin (1) and (-)-renieramycin G (2) has been accomplished in 25 and 23 steps, respectively, from 5-benzyloxy-2,4-dimethoxy-3-methyl-benzyl alcohol. The synthesis features a substrate-tunable stereoselective intramolecular Pictet-Spengler-type reaction for the construction of the key pentacyclic core of both targets, bearing either the natural configuration or the epimeric configuration at C-3. With access to a C-3 epi-pentacyclic framework, 3-epi-jorumycin (32) and 3-epi-renieramycin G (34) were also successfully synthesized. Furthermore, preliminary biological evaluation of 3-epi-jorumycin (32), in addition to relevant synthetic intermediates, revealed that significant cytotoxicity had been retained in these compounds. Therefore, these early studies constitute the basis for a new structure activity relationship (SAR) investigation for this class of antitumor antibiotics.
Lane
Jonathan W
JW
Department of Chemistry, and University of Colorado Cancer Center, Colorado State University, Fort Collins, Colorado 80523, USA.
Chen
Yuyin
Y
Williams
Robert M
RM
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000145:classification; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis*
C507299:3-epi-jorumycin; C507298:3-epi-renieramycin G; D000903:Antibiotics, Antineoplastic; D044005:Tetrahydroisoquinolines; C507297:jorumycin; C507294:renieramycin G