X‐Ray Crystal Structure Analysis of Oxindole Alkaloids

Abstract

The single-crystal X-ray structures of speciophylline, mitraphylline, and rhynchophylline, oxindole alkaloids from the Peruvian climbing vine Uncaria tomentosa (Rubiaceae), were determined. The three compounds show N ¥¥¥ HÀN hydrogen bonding, which has not been observed in the crystal structures of the related alkaloids pteropodine and isopteropodine. In the tetracyclic alkaloid rhynchophylline, the side chain is rotated out of the ring plane into a position perpendicular to it. This is in contrast to the situation of the pentacyclic analogue mitraphylline, which possesses a conformationally rigid tricyclic core. This conformational difference possibly causes the competitive antagonism of these two types of alkaloids.Introduction. ± The genus Uncaria (Rubiaceae) is a rich source of oxindole alkaloids. During recent years, pharmacological activities of some of these alkaloids were investigated. The tetracyclic oxindole alkaloid rhynchophylline (1) blocks the release of calcium from intracellular storage and possesses hypotensive potency [1]. Effects of 1 on contraction of isolated rat uterus, contraction of rabbit aorta, and myocardial contractility in dogs and cats were reported [2]. Negatively chronotropic and inotropic effects of rhynchophylline (1) and isorhynchophylline were observed [3]. In contrast, pentacyclic oxindole alkaloids affect the cellular immune system. They stimulate endothelial cells in vitro to produce a lymphocyte-proliferation-regulating factor [4] and stimulate interleukin-1 and -6 production by alveolar macrophages [5]. Isopteropodine (2) and pteropodine (3) enhance the phagocytic activity of granulocytes [6]. A recent study showed that the tetracyclic alkaloids antagonize the stimulating effect of the pentacyclic alkaloids [7]. Therefore, it seemed to be of interest to examine their three-dimensional structures in detail. The results of single-crystal Xray structure determinations of rhynchophylline (1), speciophylline (4), and mitraphylline (5), isolated from Peruvian U. tomentosa (Willd.) DC root [8] are presented. Crystal structures were reported earlier for pteropodine hydrate [9], isopteropodine, and the CHCl 3 solvate of pteropodine [10], and the related isorhynchophyllic acid from U. sinensis (Oliv. ) Havil. [11]. Mitraphylline was also detected in leaves of U. quadrangularis Geddes ( U. homomalla Miq.), U. attenuata Korth., U. orientalis Guill., U. velutina Havil., U. perrottetii (A. Rich. ) Merr., in the root of U. guianensis (Aubl.) Gmel., and in the bark of U. elliptica R. Br. [12] [13]. Speciophylline, pteropodine, and isopteropodine were also identified in the leaves of U. homomalla, U. lanosa var. glabrata (Bl.) Ridsd., U. sinensis, and U. orientalis [12] [14]. Rhynchophylline (1) was also found in the leaves of U. borneensis Havil., U. longiflora (Poir.) Merr., U. guianensis, U. macrophylla Wall., in aerial parts of U. rhynchophylla Miq., and in the stem bark and hooks of U. attenuata [12] [15].

A New 9-Methoxyyohimbine-Type Indole Alkaloid from Mitragyna africanus

“…From the aqueous methanolic extract of the stem bark of M. africanus collected in Nigeria, seven Corynanthetype oxindole alkaloids, i.e., rhynchophylline, 7) isorhynchophylline, 7) corynoxeine, 8) isocorynoxeine, 8) ciliaphylline, 8) rhynchociline, 8) and isospecionoxeine, 8) were isolated. In addition, three lignans, i.e., (ϩ)-dihydrodehydrodiconiferyl alcohol, 9) (ϩ)-isolariciresinol, 10) and (ϩ)-isolariciresinol-3a-O-b-D-glucopyranoside, 11) two secoiridoids, i.e., sweroside 12) and dihydroepinaucledal 2 13) (first example as natural product), scopoletin, and quinovic acid 3b-O-b-6-deoxy-D-glucopyranosyl-28-b-D-glucopyranosyl ester 14) were obtained.…”

New heteroyohimbine-type oxindole alkaloid from the leaves of Thai Mitragyna hirsuta

“…From the methanol (MeOH) extract of the leaves of Mitragyna hirsuta collected in Thailand one new heteroyohimbine-type oxindole alkaloid, isomitraphyllinol (1), was isolated, together with four heteroyohimbinetype oxindole alkaloids, i.e., mitraphylline (2) [12,13], isomitraphylline (3) [12], isomitraphylline N-oxide (4) [14], and isopteropodine (5) [12], and one Corynanthetype oxindole alkaloid, rhynchophylline (6) [13,15] (Fig. 1).…”

Chemistry of Indole Alkaloids Related to the Corynanthe-Type from Uncaria, Nauclea and Mitragyna Plants

“…(8). Comparison of those spectra with those of known alkaloids, rhynchophylline (6) with C7(R) [25] and isorhynchophylline (8) with C7(S), indicated that the spiro center of 31 and 32 had the S configuration. The C3 stereochemistry was elucidated by NOE experiments.…”