Total Synthesis of Tropoloisoquinolines:  Imerubrine, Isoimerubrine, and Grandirubrine¹

Abstract

A unified, ready access to the tropoloisoquinoline alkaloids imerubrine (1), grandirubrine (2), and isoimerubrine (3) is delineated and features sequential application of the intramolecular Diels-Alder reaction of an acetylene-tethered oxazole and the [4 + 3] cycloaddition of an oxyallyl. A regioselective synthesis of 1 was achieved by stereo- and regioselective oxidation of an 8-oxabicyclo[3.2.1]oct-6-en-3-one cycloadduct by means of the Moriarty method. Such a post-cycloaddition functionalization complements the synthetic utility of an alpha-alkoxy-substituted oxyallyl so as to broaden the scope of the oxyallyl [4 + 3] cycloaddition reaction.

Plant Troponoids: Chemistry, Biological Activity, and Biosynthesis

“…The prominence of these alkaloids in search for more biologically active and chemotherapeutically useful leads was limited by the scarcity of the natural isolates (about 0.0004 % from Cissampelos pareira). Recently, chemical synthesis of pareitropone [241], imerubrine, isoimerubrine, and grandirubrine [242] has been accomplished and may help to obtain more materials for further biological activity study.…”

Synthesis of naturally occurring tropones and tropolones

“…249 Cha applied this method to the synthesis of colchicine 250–251 and tropoloisoquinolines. 252 The key [4+3] cycloaddition between substituted furan 69-3 and silyl enol ether 69-1 was carried out in the presence of TMSOTf. Only one diastereomer ( 69-4 ) was observed with the desired regioselectivity.…”

The Cycloaddition Strategy for the Synthesis of Natural Products Containing Carbocyclic Seven‐Membered Rings

“…Although colchicine is the best known of the tropolone-containing natural products, other related targets have become of interest in recent years. Cha was able to utilize the methodology used for the colchicine synthesis in a total synthesis of imerubrine, [17] an unusual tropoloisoquinoline natural product (Scheme 10).…”