General strategy for the syntheses of corynanthe, tacaman, and oxindole alkaloids.
We report herein the total synthesis of the corynanthe alkaloid dihydrocorynantheol and the formal syntheses of the indole alkaloids tacamonine, rhynchophylline, and hirsutine. The strategies for assembling the corynanthe and tacaman skeletal frameworks comprised of both the classical ABD --> ABCD and ABC --> ABCD approaches wherein the variously substituted piperidinone D-rings were formed via ring-closing metathesis (RCM) followed by a 1,4-addition to introduce the requisite side chain at C(15). Since 1,4-additions to alpha,beta-unsaturated lactams represent an underdeveloped field, we conducted a series of studies with two unsaturated lactams employing organocuprates and metal enolates as the nucleophiles. These studies revealed that organocuprates derived from Grignard reagents and either stoichiometric amounts of CuCN or catalytic amounts of CuBr.DMS complex are excellent nucleophiles for such additions; TMSCl was a crucial additive for optimizing these reactions. The anion derived from ethyl 1,3-dithiolane-2-carboxylate was also an excellent nucleophile in these 1,4-additions, although the stereochemistry of such 1,4-additions to carboline-derived, unsaturated lactams was sensitive to substitution on the indole nitrogen atom. The ABD --> ABCD approach to these alkaloids featured a novel one-pot sequence of an RCM reaction and a zirconocene-catalyzed carbomagnesation followed by a second RCM to generate the D-ring.
Deiters
Alexander
A
Department of Chemistry and Biochemistry, University of Texas, Austin, Texas 78712, USA.
Pettersson
Martin
M
Martin
Stephen F
SF
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry*; D026121:Indole Alkaloids / Q000138:chemical synthesis / Q000737:chemistry; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D000078183:Oxindoles; D032068:Pausinystalia; D010880:Piperidines / Q000737:chemistry
D000470:Alkaloids; D026121:Indole Alkaloids; D007211:Indoles; D007769:Lactams; D000078183:Oxindoles; D010880:Piperidines; C520379:tacaman; C449743:tacamonine; C007398:dihydrocorynantheol; C052714:rhyncophylline; C030374:indole