Enantioselective total synthesis of (+)-dibromophakellstatin.
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.
Poullennec
Karine G
KG
Department of Chemistry, Texas A&M University, College Station, Texas 77842-3012, USA.
Romo
Daniel
D
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D007093:Imidazoles; C104805:dibromophakellstatin