Synthesis of the Enantiomers of Tedanalactam and the First Total Synthesis and Configurational Assignment of (+)-Piplaroxide

Abstract

Highlighting the recently established methodology for the direct synthesis of glycidic amides from tertiary allyl amines, the synthesis of the enantiomers of tedanalactam were completed in two steps from the corresponding chiral dihydropiperidine. Additionally, the (+)- and (-)-enantiomers of piplaroxide were obtained from their respective tedanalactam precursor, and the absolute configuration of the naturally occurring (+)-piplaroxide was determined. The present approach represents not only the shortest synthesis of (-)-tedanalactam but also the first total synthesis of (+)-piplaroxide, a repellent against the leafcutter ant Atta cephalotes.

A 5 + 1 Protic Acid Assisted Aza-Pummerer Approach for Synthesis of 4-Chloropiperidines from Homoallylic Amines

“…The reagent HCl·DMPU was prepared as reported in the literature. , Some of the starting materials and products, 1a , 1e , 1b , 1c , 1d , 1f , 1e , 1k , 1aa , 1ag , 1ab , 1ae , 1ah , 3a , 3e , 3f , 2a , 2aa , 2ae , and 2ag , are commercially available or reported compounds, and their spectroscopic data agree well with the reported literature.…”

Transition-Metal-Free Functionalization of Saturated and Unsaturated Amines to Bioactive Alkaloids Mediated by Sodium Chlorite

“…28 In contrast to these methodologies the tandem C-H oxidation-double-bond epoxidation reaction of chiral dihydropiperidine 31, which was prepared in three steps from amine 30, to the corresponding glycidic amides 32a and 32b was achieved in good yield (Scheme 7b). 29 Scheme 7 (a) Naturally occurring compounds featuring the 3,4-epoxy-2-piperidone motif; (b) five-step synthesis of both enantiomers of tedanalactam and the first total synthesis and absolute configurational assignment of (+)-piplaroxide Synthesis of (-)-27 was accomplished through debenzylation of 32a. Since the absolute configuration of naturally occurring (-)-tedanalactam 27 was known, the absolute configurational assignment of (+)-piplaroxide (28) was de-…”

“…Although the above-mentioned syntheses were nonselective by using the chiral auxiliary strategy, the synthesis of (-)-3,4-epoxy-5-pipermethystine (29) offered the possibility to develop a substrate-controlled asymmetric total synthesis and configurational assignment of an important secondary metabolite of kava [(-)-3,4-epoxy-5-pipermethystine (29)]. 30 Since the acetoxy group at C5 was proposed to be found anti-oriented to the oxirane ring within the piperidone ring of 29, the carbohydrate-derived dehydropiperidine 34 was presented as a suitable chiral precursor.…”

Transition-Metal-Free Total Synthesis and Revision of the Absolute Configuration of Pipermethystine

“…Therefore, eliminating the use of transition or precious metals would contribute to the development of a greener and more sustainable synthesis, which is desirable for the pharmaceutical production processes. In this regard, our research group has developed efficient, accessible, economical, and environmentally friendly protocols for the functionalization of simple N -heterocycle substrates into relevant bioactive alkaloids …”