A New Stereocontrolled Total Synthesis of the Mast Cell inhibitory Alkaloid, (+)-Monanchorin, via the Wittig Reaction of a Stabilized Ylide with a Cyclic Guanidine Hemiaminal

Abstract Image

An asymmetric total synthesis of the mast cell inhibitor (+)-monanchorin is reported in which a Sharpless AD on 11 and a cyclic sulfate ring opening with an azide feature as key steps. After further manipulation, a novel guanidine-controlled ester reduction provided the guanidine-hemiaminal 25 which underwent Wittig olefination to give 27. Hydrogenation and a second guanidine-controlled reduction of the ester in 28, to obtain aldehyde 29, then set up a trifluoroacetic acid mediated cyclization to give (+)-monanchorin TFA salt.

Total Synthesis of the Antitumor Macrolides, (+)-Brefeldin A and 4‑Epi-Brefeldin A from D‑Glucose: Use of the Padwa Anionic Allenylsulfone [3+2]-Cycloadditive Elimination To Construct Trans-Configured Chiral Cyclopentane Systems

A new synthesis of (+)-brefeldin A is reported via Padwa allenylsulfone [3+2]-cycloadditive elimination. Cycloadduct 13 was initially elaborated into iodide
27, which, following treatment with Zn, gave aldehyde 28 whose C(9) stereocenter was epimerized. Further elaboration into enoate 38 and Julia−Kocienski olefination with 5 subsequently afforded 39, which was deprotected at C(1) and O(15). Yamaguchi macrolactonization of the seco-acid thereafter afforded a macrocycle that underwent O-desilylation and inversion at C(4) to give (+)-brefeldin A following deprotection