Protoverbine, the Parent Member of a Class of Macrocyclic Spermine Alkaloids

Abstract

The 17‐membered macrocyclic spermine alkaloids protoverbine ((8S)‐8‐phenyl‐1,5,9,13‐tetraazacycloheptadecan‐6‐one, 1) and its N(9),N(13)‐methylene‐bridged derivative protomethine ((2S)‐2‐phenyl‐1,5,9,14‐tetraazabicyclo[12.3.1]octadecan‐4‐one, 2) were isolated from Verbascum pseudonobile Stoj. et Stef. (Scrophulariaceae) and characterized. The synthesis of their racemates is described. The possible role of (S)‐protoverbine (1) and (S)‐protomethine (2) as precursors in the biogenesis of the whole class of N(1),N(9)‐ and/or N(13)‐substituted alkaloids, the groups of verbamethine ((S)‐3a – f), verbacine ((S)‐4a – f), incasine B′/verdoline ((S)‐5a – f), verbamedine ((S)‐6a – f), and verbascenine ((S)‐7a – f), is discussed.

Biogenesis and function of macrocyclic spermine alkaloids

“…1), which are analogous to the here expected terminal precursor 8 of aphelandrine (9). 14,15 This fact suggests that this metabolic reaction sequence, occurring in different plant families, is widely spread in nature. For this reason aphelandrine is proposed to be formed from 8.…”

“…The similarly constituted alkaloids protoverbine (6) (4′-unsubstituted analogue of prelandrine, 5) and buchnerine (7) (O-methylated analogue of prelandrine, 5) were isolated earlier from different Verbascum species (Scrophulariaceae) 14,15 and Clerodendrum buchneri (Verbenaceae). 24 Subsequently enzymatic studies led to the detection of spermine (3) and spermidine (2) hydroxycinnamoyl transferases in the cell free extract from the stems of Aphelandra tetragona.…”

Functionalisation of Macroheterocycles with Preserving and Changing Their Sizes

“…The presence of additional functional groups at one or several nitrogen atoms broadens chelating properties and allows regulating solubility and behaviour in solutions. [22][23][24][25][26][27] N-Functionalized triazamacrocycles that are prepared mostly by N-alkylation reaction [28][29][30][31] are especially attractive compounds to prepare selective ligands that coordinate transition metals.…”

Phenol oxidative coupling in the biogenesis of the macrocyclic spermine alkaloids aphelandrine and orantine in Aphelandra sp.

“…et Stef. (Scrophulariaceae; Guggisberg et al 2000) and buchnerine (the 4¢-methoxylated analog of prelandrine, 4) from Clerodendrum buchneri (Verbenaceae; Lumbu and Hootele 1993). The di-O-methylated analog of the here-postulated terminal precursor (S)-dihydroxyverbacine (3) is an (E)-isomer of (S)-(Z)-4-methoxycinnamoyl buchnerine, which is a naturally occurring alkaloid identi®ed in C. buchneri (Verbenaceae; Lumbu and Hootele 1993).…”