Highly Diastereoselective Desymmetrizations of Cyclo(Pro,Pro):  An Enantioselective Strategy toward Phakellstatin and Phakellin

Abstract

[reaction: see text] Monoenolates of C(2)-symmetric, proline-derived piperazine-2,5-diones were generated and trapped with a variety of electrophiles to produce, in a highly diastereoselective fashion, functionalized diketopiperazines (DKPs). These reactions provide the basis for an asymmetric, desymmetrization strategy toward the marine alkaloids phakellstatin and phakellin. The relative stereochemistry of the functionalized DKPs was confirmed by single-crystal X-ray analysis and/or NOE experiments. Bis-functionalization of the DKPs was also found to proceed with high levels of diastereoselectivity.

From anti-fouling to biofilm inhibition: New cytotoxic secondary metabolites from two Indonesian Agelas sponges

“…39a The phakellins, one of the unique members of pyrrole imidazole metabolites (4 and 5), exhibit a unique array of functionalities including a cyclic guanidine, a pyrrole carboxylic acid, a pyrrolidine, and a congener with vicinal diaminal stereocenters. 62 Oroidin is structurally related to (À)-dibromophakellin by a complex cyclisation of oroidin that formally connects the pyrrole nitrogen atom (N-1) to the unalkylated aminoimidazole carbon (C-12) and the amino nitrogen atom (N-7). Whereas in dibromohydroxyphakellin (5) and dibromophakellin HCl (4), the linear chain is cyclised to form a pyrrolopyrazinone ring, in agelanesins, the imidazole ring is replaced with a halogenated tyramine.…”

New Hope on Drug Leads Development From Deep Ocean: Halogenated Alkaloids of Agelas Sponges

“…(Fedoreyev et al, 1989). The phakellins itself exhibit a unique array of functionality including a cyclic guanidine, a pyrrole carboxylic acid, a pyrrolidine, and a congener with potentially delicate vicinal diaminal stereocenters (Poullennec et al, 2002).…”

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

“…Multiplying Eqns (7), (8), (9), (10), and (11) by a factor of 10 and Eqns (12), (13), (14), and (15) by a factor of five and Eqn (16) by a factor of two, and then summing them with each other results in the overall reaction with the stiochiometry satisfied. In agreement with the above scheme, assuming a steady state approximation for X þ 1 , the rate equation obtained for the uncatalysed process is…”