Synthesis of NP25302

Abstract

An efficient synthesis of NP25302 is presented that relies on 5-endo-dig N-cyclization to establish the bicyclic core and Curtius rearrangement to install the N-acyl vinylogous urea functionality.

Discovery of a Single Monooxygenase that Catalyzes Carbamate Formation and Ring Contraction in the Biosynthesis of the Legonmycins

“…In contrast to the widely distributed plant PAs, only 10 bacterial PAs have been discovered thus far, including the clazamycins,4 bohemamines,5 and jenamidines (Supporting Information, Figure S1) 6. Bacterial PAs possess promising antibacterial and antitumor activities6 and have attracted considerable interest from academic research groups and the pharmaceutical industry 7. However, the biosynthetic origin of bacterial PAs has not been disclosed thus far.…”

Structure, Biosynthesis, and Occurrence of Bacterial Pyrrolizidine Alkaloids

“…[1,2] More than 600 derivatives are known from over 6000 different plant species,and they are probably responsible for half of the loss of domestic livestock and countless reports on acute and chronic human food poisoning owing to their high toxicity. [1] Despite the infamous "success" of these PA toxins,o nly afew PA derivatives that originate from non-plant organisms have been described, namely the clazamycins, [3,4] jenamidines, [5,6] bohemamine, [7] and NP25302, [8] which have all been isolated from Streptomyces.W hereas PA biosynthesis in plants includes homospermidine cyclization, [9][10][11] nothing is known about bacterial PA biosynthesis.…”

Gold(I)‐Catalyzed N‐Desulfonylative Amination versus N‐to‐O 1,5‐Sulfonyl Migration: A Versatile Approach to 1‐Azabicycloalkanes

“…Under conditions reported for some heteroaryl tosylates, but without further optimization, these two compounds could be coupled to produce the arylated product 7 in good yield (Scheme , top). To further illustrate the power of the gold‐catalyzed N‐desulfonylative amination in organic synthesis, we carried out a formal synthesis of (+)‐ nor ‐NP25 302, a possible antileukemia agent (Scheme , bottom) . For this purpose, the enantiomerically pure pyrrolidine 1 p was prepared and treated with a gold catalyst and meta ‐nitrophenol under the conditions described above.…”