Enantioselective Total Synthesis of (+)-Dibromophakellstatin

Abstract

The first enantioselective total synthesis of (+)-phakellstatin and (+)-dibromophakellstatin was achieved. Key steps in the synthesis were a desymmetrization of the diketopiperazine (S,S)-cyclo (Pro, Pro) via a diastereoselective acylation, an intramolecular Mitsunobu reaction to introduce the C6 aminal, and a tandem Hofmann rearrangement/cyclization to simultaneously introduce the C10 quaternary aminal center and deliver the cyclic urea. The synthesis also demonstrates the unusual stability of pyrrolo aminals. Importantly, this strategy has the potential for producing phakellstatin derivatives, derived from (R,R)-cyclo (Pro, Pro), necessary for biological studies. A similar annulation protocol is also expected to be applicable to the synthesis of palau'amine.

Kinetics and Mechanism of the Kmn04-Oxidative Catalysed Condensation Reaction of L-Proline to a Diketopiperazine: Evidence for Delayed Autocatalytic Behaviour

“…13 C NMR spectrum shows five types of carbons, while the MS spectrum verifies that the compound mass is equal to proposed proline-derived DKP. All the above data corroborate those reported elsewhere [7,13,43].…”

Omphalotins E–I, Five Oxidatively Modified Nematicidal Cyclopeptides from Omphalotus olearius

“…[9] Whereas neither omphalotin A, tryptophan nor 1 gave any reaction, 2 produced the same vermillion colour as hydroxylamine hydrochloride even at low concentrations. When an analytical sample of 2 was reduced with TiCl 3 in methanolic solution, [10] the formation of 1 could be detected by TLC, [11] 1 H NMR spectroscopy and HPLC-MS, further confirming the presence of the Nhydroxylated tryptophan derivative in omphalotin F (2).…”

Biomimetic Synthesis of Marine Pyrrole‐2‐Aminoimidazole and Guanidinium Alkaloids

“…In 2008, Romo [36], and later Nagasawa [37], reported the enantioselective syntheses of (+)-phakellin starting from l-proline to construct the pyrrole-proline ketopiperazine moiety of dibromophakellin (7). The same strategy was employed for the first asymmetric synthesis of the close (+)-phakellin derivative (+)-phakellstatin by Romo in 2003 [38]. The synthesis confirmed the absolute configuration of the natural product, which is (−)-phakellstatin (hydrolyzed phakellin).…”