A Concise Stereoselective Synthesis of Preussin, 3-epi-Preussin, and Analogues

Abstract

[reaction: see text] A new stereoselective synthesis of the antifungal and antitumor agents Preussin and 3-epi-Preussin via a Pd-catalyzed carboamination of a protected amino alcohol is described. The key transformation leads to simultaneous formation of the N-C2 bond and the C1'-aryl bond, and allows installation of the aryl group one step from the end of the sequence. This strategy permits the facile construction of a variety of preussin analogues bearing different aromatic groups.

Palladium‐Catalyzed Carboetherification and Carboamination Reactions of γ‐Hydroxy‐ and γ‐Aminoalkenes for the Synthesis of Tetrahydrofurans and Pyrrolidines

“…[41] In order to further illustrate the scope and utility of this method, we elected to pursue a total synthesis of the alkaloid natural product (+)-preussin (3). [42] This compound was first isolated in 1988 from the fermentation extracts of Preussia sp. and Aspergillis ochraceus, [7a] and was initially reported to possess modest antifungal activity.…”

Application of a 5-endo-trig cyclisation in the total synthesis of (+)-preussin

“…We were keen to demonstrate the synthetic utility of our adapted 5-endo trig methodology, and the natural product (+)-preussin, 1 [13][14][15] appeared to be an excellent target with its 2,5-syn disubstituted pyrrolidine core. Our initial retrosynthetic analysis is illustrated in Scheme 4.…”

Synthesis of Saturated Five‐Membered Nitrogen Heterocycles via Pd‐Catalyzed CN Bond‐Forming Reactions

“…(1.15)) [36e]. This method has been applied to a stereocontrolled synthesis of ( þ )-preussin [37], and is also effective with substrates bearing disubstituted alkenes (Eq. (1.16)) [36f ].…”