Total Synthesis of (+)-Epilupinine via An Intramolecular Nitrile Oxide-Alkene Cycloaddition

Abstract

Total synthesis of (+)-epilupinine was accomplished in nine steps and in 48% overall yield, in which INOC was used as the key step for the construction of the quinolizidine skeleton. We found that it was an extremely difficult task to prepare the key intermediates (R)-N-(3-nitropropyl)-2-vinylpiperidine or (R)-(2-vinylpiperid-1-yl)propanal by routine methods. Thus, by using Fukuyama's oxime synthesis, a general method was developed for highly efficient conversion of 3-(N,N-dialkylamino)propanols into 3-(N,N-dialkylamino)propanal oximes without using the corresponding aldehydes.

Total Synthesis of (−)‐Lepadin F based on a Stereoselective Diels–Alder Reaction Controlled by a Ketolactone‐type Dienophile

“…We then focused on advancing the cycloadduct toward the synthesis of lepadin F. The deoxygenation of ketone 8 wasa ttempted to obtain methylene product 13 first. Unfortunately, the classical methods, such as Caglioti-Wolff-Kishner reduction, [20] thioacetal-based reduction, [21] Yamamura-Clemmensen reduction, [22] and its Arimoto variant, [23] all were unsuccessful. Thus, triol 9 was employedt oa chieve the subsequents ynthesis (Scheme 3).…”

Total Syntheses of (−) Epilupinine and (−)-Tashiromine Using Imino-Aldol Reactions

“…(+)-Epilupinine has been shown to exhibit in vitro inhibitory activity against Leukaemia P-388 (LD50 = 28 μg/mL) and lymphocytic Leukaemia L1210 (LD50 = 28 μg/mL) cells . Both natural products have been the focus of considerable synthetic attention and have been prepared by total synthesis in racemic and enantiomerically enriched form. − …”

Oxidation of oximes with hypervalent iodine reagents: opportunities, development, and applications

“…An instructive example of what might happen in the absence of protonic catalysis emerges from the work of Wang, Hu, and collaborators, who found that the treatment of oxime 50 with DIB in methanol / catalytic TFA failed to produce the desired 51 (Scheme 14; decomposition of 50). 22 It is likely that the basic amine neutralized the TFA, thereby denying protonic catalysis to the process and opening the door to side reactions. A limitation of the above methodology is that the formation of isoxazoles from terminal alkynes is inefficient.…”