Total Synthesis of a Marine Alkaloid from the Tunicate Dendrodoa grossularia

Abstract

A short synthesis of an indole marine alkaloid (1) from the tunicate Dendrodoa grossularia is described. The key step in the synthesis involves a novel twist on an underutilized oxazole rearrangement, which produces the quaternary stereocenter in the molecule.

Muscarine, imidazole, oxazole, and thiazole alkaloids

“…138 By applying a Claisen-type oxazole rearrangement, the quaternary imidazolone scaffold of 147, a unique marine-derived alkaloid from the tunicate Dendrodoa grossularia, was efficiently produced. [139][140][141] Diterpene alkaloids sarcodictyins A 148 and B 149, and eleutherobin 150, isolated from the soft corals Sarcodictyon roseum and Eleutherobia sp., respectively, have a common oxatricyclic ring system of the 4,7-oxaeunicellane skeleton. Synthesis of the central 10-membered ring system of these alkaloids has been achieved by the NiCl 2 /CrCl 2 -mediated intramolecular Nozaki-Hiyama-Kishi coupling reaction.…”

The preparation of (4H)-imidazol-4-ones and their application in the total synthesis of natural products

“…The first total synthesis of compound 1 was completed by Hupp and Tepe in 2008 (Scheme 35). 140,141 In this synthesis, the quaternary carbon was formed via a oxazole rearrangement reaction, which produced an hydantoin product. The hydantoin was then converted into a thiohydantoin, which was reacted to form a 2-aminoimidazolone through standard conditions.…”

Reactivity of Oxazol-5-(4H)-ones and Their Application toward Natural Product Synthesis

“…[59][60][61][62][63][64] Our group has recently reported the total synthesis of a marine alkaloid from the tunicate Dendrodoa grossularia 65 via a novel oxazole rearrangement. 66 The substituted hydantoin intermediate could serve as the building block to the desired imidazolone scaffold, and act as a synthetic handle with which we could replace the carbonyl in the 2-position of the hydantoin with potentially any amine, giving access to various analogues.…”

“…As a result, four indole alkaloids were isolated and tested, with variable results. 75,76 As part of our laboratory's focus on the syntheses of pharmacologically significant scaffolds, we have recently reported the first total synthesis of the indole alkaloid 15, 66 as well as two additional analogues. 73 The synthetic route The versatility of the synthetic pathway developed for the natural product was illustrated by the synthesis of two analogues that required no major modification of the original synthetic route.…”

“…The same deprotection method that was previously used with the natural product, was used to produce imidazolone 37. After oxidation of the terminal alkene by previously determined conditions, 66 the synthesis of 38 was completed. 73…”