The Alkaloids

Chemistry and Biology
1. Auflage 2008
ISBN: 978-0-08-092303-1
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, Band Volume 66, 276 Seiten

Reihe: The Alkaloids

This series is world-renowned as the leading compilation of current reviews of this vast field. Internationally acclaimed for more than 40 years, The Alkaloids: Chemistry and Biology, founded by the late Professor R.H.F. Manske, continues to provide outstanding coverage of this rapidly expanding field. Each volume provides, through its distinguished authors, up-to-date and detailed coverage of particular classes or sources of alkaloids. - Up-to-date reviews on a large and very important group of natural products from both a chemical and biological perspective - Comprehensive, dynamic reviews written by leading authors in the respective fields - Broad coverage on the biological aspects

Autoren/Hrsg.

Leseproben

Chapter 1 Alkaloids of Kopsia
Toh-Seok Kam*; Kuan-Hon Lim    Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia
* Corresponding author. email address: [e-mail] Publisher Summary
This chapter presents a review on the chemistry and pharmacology of some recent Kopsia alkaloids and discusses the alkaloid structure type, in order of increasing complexity, and approximately along the lines of a progressing biosynthetic pathway. In each discussion, the aspects of structure elucidation, chemistry, synthesis, and biological activity of the alkaloids concerned explained. The occurrences of alkaloids in Kopsia species that have been chemically investigated are summarized in the chapter. The monoterpene alkaloids constitute a relatively small group of compounds and occur in several species, including K. pauciflora, K. profunda (K. macrophylla), and K. dasyrachis, from which several new monoterpene alkaloids related to skytanthine have been recently isolated. The North Borneo species K. pauciflora provided six such monoterpene alkaloids—namely, kinabalurines A–F. Kinabalurine G was isolated from the leaf extract of K. dasyrachis, another Kopsia from Malaysian Borneo. K. profunda (K. macrophylla) provided two more new monoterpene alkaloids, kopsilactone and kopsone, in addition to the known alkaloids 5,22-dioxokopsane, dregamine, akuammiline, tabernaemontanine, deacetylakuammiline, norpleiomutine, and kopsoffine. The leaves of K. dasyrachis also gave kopsirachine, which is constituted from union of the flavonoid, catechin, and two units of skytanthine. Nitaphylline was the only bisindole isolated from K. teoi, which otherwise yielded a large number of new indole alkaloids. I Introduction
Plants of the genus Kopsia (Apocynaceae) are distributed from southern China and Burma to northern Australia and Vanuatu. The genus is, however, most diverse in Peninsular Malaysia and Sarawak (Malaysian Borneo) (1). All species are shrubs or small trees, and due to their attractive appearance (the most distinguishing feature being the showy white flowers with red, pink, or yellow “eyes”), a number have become widely cultivated as garden or ornamental plants. The genus was first published in 1823 by Blume in honor of the Dutch botanist J. Kops, with one species K. arborea (2). Later botanical studies include a preliminary partial revision by Markgraf (3) and a chemotaxonomic study by Sévenet et al. (4). The most recent and comprehensive revision of the genus, however, is that of Middleton in which 24 species are recognized and four new species are described (1,5). In this review, we shall follow the classification according to Middleton (1), with the species attributed in the original reports cited in parenthesis. The first Kopsia alkaloid isolated was kopsine (1) (6). The structure was, however, only solved in the 1960s after considerable classical degradation studies coupled with the introduction of high-resolution mass spectrometry (7–17). Additional confirmation was later provided by chemical correlation of kopsine with minovincine (18), as well as by X-ray crystallographic analysis of the methyl iodide salt of (-)-kopsanone (19,20). Other notable examples of early Kopsia alkaloids include fruticosine (2) and fruticosamine (3) from K. fruticosa (14,21–25), and kopsingine (4) from K. singapurensis (26). These alkaloids have also been discussed in previous volumes of this, as well as other, series (27–31). In more recent times, plants of this genus have proven to be fertile sources of many alkaloids with unusual and fascinating molecular structures, as well as interesting biological activities, and a review chapter devoted exclusively to the Kopsia alkaloids appears timely. The present review shall therefore focus on the chemistry and pharmacology of these more recent Kopsia alkaloids. The organization of the chapter will be based on the alkaloid structure type, in order of increasing complexity, and approximately along the lines of a progressing biosynthetic pathway. Under each section, aspects of structure elucidation, chemistry, synthesis, and biological activity of the alkaloids concerned will be addressed. Finally, the occurrence of alkaloids in Kopsia species which have been chemically investigated will be summarized. II Monoterpene Alkaloids
The monoterpene alkaloids constitute a relatively small group of compounds and occur in several species, including K. pauciflora, K. profunda (K. macrophylla), and K. dasyrachis, from which several new monoterpene alkaloids (5–13) related to skytanthine have been recently isolated. The North Borneo species K. pauciflora provided six such monoterpene alkaloids, namely, kinabalurines A–F (5–10), which are hydroxyskytanthine derivatives (32,33). The first alkaloid isolated was kinabalurine A (5), which was obtained as colorless plates. The mass spectrum showed a molecular ion at m/z 183 (C11H21NO) accompanied by fragments due to loss of H, Me, and OH, and other fragments at m/z 84, 58, and 44, characteristic of skytanthine-type alkaloids. The IR spectrum indicated the presence of a hydroxyl group (3357 cm-1), and this was supported by the presence of an OH resonance ca. d 3.27 in the 1H NMR spectrum. The 13C NMR spectrum accounted for all 11 carbon atoms and the presence of an oxymethine was confirmed by the resonance at d 80.0. Other significant peaks in the 1H NMR spectrum included a pair of three-H doublets at d 0.97 and 1.06, corresponding to two CH3CH– groups, and an N-methyl singlet at d 2.25. The spectral data thus suggested that kinabalurine A is a hydroxyskytanthine derivative, and COSY and HETCOR experiments confirmed that hydroxy substitution was at C(7) and allowed the full assignments of the NMR spectral data. In addition, the observed J1–9 value of 10 Hz required a trans ring junction. The NMR data, however, were insufficient to establish the stereochemistry completely and unequivocally and for this purpose X-ray diffraction analysis was undertaken, which established the structure of kinabalurine A. Kinabalurine A was the second 7-hydroxyskytanthine reported, the first being incarvilline (14) isolated from the Chinese plant Incarvillea sinensis. The structure of incarvilline was also established by X-ray analysis (34). Kinabalurine A differs from incarvilline in having a trans ring junction, a 7ß-OH substituent, and a 4a-methyl group. Kinabalurine B (6) is the 7-oxo derivative of kinabalurine A as shown by the spectral data, as well as by its ready formation via oxidation of kinabalurine A. Similarly, kinabalurine C (7) was readily shown to be the N-demethyl derivative of kinabalurine B from the spectral data (loss of the N-methyl signal in the 1H and 13C NMR, and the presence of a secondary amine absorption in the IR at 3400 cm-1). The trans ring junction in kinabalurine C was clearly shown in the 600 MHz 1H NMR spectrum, which showed the H(9) signal as a quartet of doublets (J5ß–9a=J1ß–9a=J8ß–9a=12 Hz, J1a–9a=4 Hz). The spectral data for kinabalurine D (8) showed it to be yet another 7-hydroxyskytanthine diastereomer, but proved inadequate for definitive assignment of stereochemistry. To this end, kinabalurine D was converted to the quaternary ammonium salt, which provided suitable crystals for X-ray analysis. Kinabalurine D differs from kinabalurines A–C in having a 4ß-methyl group and a trans ring junction in which the stereochemistry of H(5) and H(9) are now reversed. Kinabalurine E (9) is the 7-oxo derivative of kinabalurine D, as shown by the spectral data and by chemical correlation (PCC oxidation) with 8. Kinabalurine F (10) was obtained in minute amounts, and its structure elucidation relied mainly on analysis of the 600 MHz NMR data and by comparison with 5, 8, and incarvilline (14). The orientation of the 7-hydroxy group of kinabalurine F was deduced to be ß based on comparison of the observed C(7) shift (d 81) with those of 5 (d 80) and 8 (d 81), which also have a 7ß-OH. The C(7) shift in incarvilline, which has a 7a-OH, was shifted upfield to about d 73. The observed NOE interactions from H(7a) to the 8-methyl and from...