Piper amides synthesis

The chemistry of pepper has long been studied and the pungent principle of black pepper—a piperidine alkaloid, piperine 134—was isolated as early as 1877 (201). Its synthesis from the acid and piperidine was accomplished in 1882. (202). The corresponding pyrrolidine alkaloid trichostachyne (135) was isolated some 100 years later from several Piper species (see below). The cooccurence of piperidine and pyrrolidine alkaloids is a common feature of the chemistry of pepper. In many cases, the crude alkaloid extract is first cleaved with acids or bases and then each alkaloid is reconstituted by selective amidation. For the sake of unity, this chapter will be limited to comments on pyrrolidines, even in cases where they are minor alkaloids. 

Attempts to prepare l-Z-lysergoyl-4-phenylpiperazine (1, Ri, R2 = (CH2CH2)2NC6H5) were unsuccessful. The expected amide was isolated in very low yield which was insufficient for complete identification. However, bis(4-phenyl-l-piper-azinyl)phosphinic chloride (4) was obtained in 32% yield. Compound 4 was identical with the product obtained from the reaction of 2 equiv of 1-phenylpiperazine with 1 equiv of POCl3 in the presence of Et. This was the only instance where compounds of type 4 were isolated from the reaction mixture in our synthesis of numerous lysergamides. 

Vandopsis longicaulis Certain tumour-inhibitory plants of the Piperaceae and Rhizophoraceae families have yielded amides, e.g. A -dibydropiperine (9) occurs in Piper novae-hollandiae Miq. Macrocyclic alkaloids, e.g. azimine (10), have been fully defined. Further evidence for the nature of Lythrum bases has been obtained by synthesis of the overall skeleton. The key step in the synthesis involved formation of the 17-membered ring (11) (12). Directions for the isolation and degradation of piperine (9, with y,5-double bond) have been included in a unique laboratory text. ... 

This chapter aims to provide a relatively comprehensive, yet inevitably not exhaustive, compilation of structures of amides isolated from Piper species (Tables 1 and 2). The chemistry and biological activity of some of these compounds as well as new developments in their synthesis are reviewed.2... 

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