Total Synthesis of (−)-Agelastatin A

Abstract

A new route to (-)-agelastatin A is reported. The requisite nitrogen functionalities of the agelastatin core have been installed by intramolecular aziridination of an azidoformate and subsequent regioselective azidation, leading to net trans-diamination of the double bond. The present synthesis also demonstrates two new protocols for the preparation of an imidazolidinone hemiaminal motif from an oxazolidinone intermediate which comprise sequential N-tert-butoxycarbonylation, urea formation, hydrolysis, and oxidative cyclization, and direct aminolysis and subsequent oxidative cyclization.

Biosynthesis, asymmetric synthesis, and pharmacology, including cellular targets, of the pyrrole-2-aminoimidazole marine alkaloids

“…84 The synthesis disclosed by Tanaka and Yoshimitsu in 2008 commenced with the hetero Diels-Alder cycloaddition of cyclopentadiene and acylnitroso dienophile 139 , followed by reductive N-O cleavage and enzymatic resolution, which delivered the enantiomerically pure C ring precursor 138 . 85 The same approach was also utilized in their second generation synthesis completed the following year. 86 Also in 2009, the strategy employed by Chida featured an elegant sequential Overman/Mislow-Evans rearrangement of bis-trichloroimidate 141 followed by ring-closing metathesis that established cyclopentene 140 .…”

A Stereodivergent Strategy to Both Product Enantiomers from the Same Enantiomer of a Stereoinducing Catalyst: Agelastatin A

“…A recent synthesis by the Ichikawa group in 2007 featured the double usage of a [3,3]‐sigmatropic rearrangement of allyl cyanate 15. In 2008, Yoshimitsu–Tanaka disclosed a new asymmetric synthesis of agelastatin A using an azidoformate‐mediated aziridination reaction 16. Most recently, a racemic synthesis was reported by Dickson and Wardrop, employing a strategy based on multiple usage of the trichloroacetamide functionality 17.…”

Formal synthesis of (−)-agelastatin A: an iron(II)-mediated cyclization strategy

“…N -Tosyloxycarbamate 8 was prepared from alcohol 6 , which was obtained by a previously reported protocol (Scheme 2) [26–27]. Alcohol 6 was first treated with CDI ( N , N ’-carbonyldiimidazole) and then with hydroxylamine hydrochloric acid salt to afford N -hydroxycarbamate 7 in 67% yield [36].…”

“…The first-generation strategy employed a stereoselective thermal aziridination of azidoformate 2 and a subsequent aziridine-opening reaction to establish the vicinal trans nitrogen motif 4 [26]. The second-generation strategy involved the radical aminobromination of azidoformate 3 followed by lactamization of the resultant bromide 5a to furnish a tetracyclic compound (structure not shown), which was transformed into the natural product [27].…”