Rahman Studies in Natural Products Chemistry

1. Auflage 2015
ISBN: 978-0-444-63470-2
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, Band Volume 44, 552 Seiten

Reihe: Studies in Natural Products Chemistry

Natural products in the plant and animal kingdom offer a huge diversity of chemical structures that are the result of biosynthetic processes that have been modulated over the millennia through genetic effects. With the rapid developments in spectroscopic techniques and accompanying advances in high-throughput screening techniques, it has become possible to isolate and then determine the structures and biological activity of natural products rapidly, thus opening up exciting opportunities in the field of new drug development to the pharmaceutical industry. The series also covers the synthesis or testing and recording of the medicinal properties of natural products, providing cutting edge accounts of the fascinating developments in the isolation, structure elucidation, synthesis, biosynthesis and pharmacology of a diverse array of bioactive natural products. - Focuses on the chemistry of bioactive natural products - Contains contributions by leading authorities in the field - Presents sources of new pharmacophores

Atta-ur-Rahman, Professor Emeritus, International Center for Chemical and Biological Sciences (H. E. J. Research Institute of Chemistry and Dr. Panjwani Center for Molecular Medicine and Drug Research), University of Karachi, Pakistan, was the Pakistan Federal Minister for Science and Technology (2000-2002), Federal Minister of Education (2002), and Chairman of the Higher Education Commission with the status of a Federal Minister from 2002-2008. He is a Fellow of the Royal Society of London (FRS) and an UNESCO Science Laureate. He is a leading scientist with more than 1283 publications in several fields of organic chemistry.

Autoren/Hrsg.

Rahman, Atta-Ur

Leseproben

Chapter 1

Terpenoids and Sterols from Mushrooms

Yasunori Yaoita*,† [e-mail]

Masao Kikuchi†

Koichi Machida*,†
*    Pharmaceutical Education Center
†    Department of Molecular Structural Analysis, Tohoku Pharmaceutical University, Sendai, Miyagi, Japan

Abstract

Sterols and triterpenoids occur in all major groups of organisms, from fungi to humans, as secondary metabolites. It has been reported that various sterols and triterpenoids isolated from mushrooms to possess inhibitory activities on inflammation induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a well-known tumor promoter, and for tumor promotion in two-stage carcinogenesis in mice. Therefore, these compounds may possibly prove useful for producing cancer chemopreventive agents. Over the past 20 years, our research group has been involved in the phytochemical study of sterols and triterpenoids from mushrooms. From 18 species, namely, Amanita pantherina, Amanita virgineoids, Daedaleopsis tricolor, Flammulina velutipes, Grifola frondosa, Hypsizigus marmoreus, Lentinula edodes, Lyophyllum shimeji, Naematoloma sublateritium, Omphalia lapidescens, Panellus serotinus, Pholiota nameko, Pleurotus eryngii, Pl. ostreatus, Polyporus umbellatus, Sarcodon aspratus, Tricholoma matustake, and T. portentosum, we isolated 28 new sterols and 3 new triterpenoids. In this review, structural features of a sterol having 5,8 structure (1), six sterols having 5a,6a-epoxy group (2–7), five sterols having 5a,9a-epidioxy group (8–12), six sterols having enone, diene, and ketone (13–18), four sterols having 3,5,6,9-tetrol and 3,5,6,7-tetrol structures (19–22), a sterol having 1,2,3,4,5,10,19-heptanor structure (23), five 23-methylergostane-type sterols (24–28), and three lanostane-type triterpenoids (29–31) are discussed. The structures of compounds 1–31 are shown below. Among these, compounds 2–4 are the first examples of a naturally occurring 5a,6a-epoxy-3ß,7ß-dihydroxy-8-sterol, a 5a,6a-epoxy-3ß,7ß,14a-trihydroxy-8-sterol, and a 5a,6a-epoxy-3ß,7a-dihydroxy-8,14-sterol, respectively. 5a,6a;8a,9a-Diepoxy-3ß,7a-dihydroxy (6) and 5a,6a;8a,9a-diepoxy-3ß,7ß-dihydr-oxy moieties (7) are unprecedented in the natural sterols previously known. Compounds 8–12 are the first example of a naturally occurring 5a,9a-epidioxy sterol. Compounds 15 and 16 are the first examples of a naturally occurring 3ß,5a,9a,14a-tetrahydroxy-7-en-6-one sterol and a 3ß,5a,9a,14ß-tetrahydroxy-7-en-6-one sterol, respectively. Compounds 17 and 18 are the first examples of a naturally occurring 3ß,5a,6ß-trihydroxy-7,9(11)-sterol and a 3ß,5a,6ß-trihydroxy-7-keto sterol, respectively. Although a sterol with the (22E,24R)-23,24-dimethyl-22-side chain has been detected in marine organisms, the isolation of a sterol with this side chain (24–28) from terrestrial sources is rare.

Keywords

Mushrooms

Sesquiterpenoids

Triterpenoids

Sterols

Meroterpenoids

Introduction

Terpenoids are widespread natural products that are formed by C5 isoprene units leading to their characteristic branched chain structure. Terpenoids are divided into families based on the number of isoprene units from which they are formed. Thus, there are monoterpenoids (C10), sesquiterpenoids (C15), diterpenoids (C20), sesterterpenoids (C25), triterpenoids (C30), and tetraterpenoids (C40). Higher polymers (polyterpenoids) are encountered in materials such as rubber. Sterols, essential eukaryotic constituents, are biosynthesized through triterpenoids [1]. Fungi are widespread, nonphotosynthetic microorganisms that play a vital role in the environment, particularly in the biodegradation of organic material. The higher fungi, the mushrooms, develop complex and readily observable structures known as fruiting bodies, which sprout from their mycelium, particularly in the autumn, and produce spores. Mushrooms are widely consumed both as foods and alternative medicines. Some fungus-specific constituents of mushrooms are thought to be effective against cancer and other lifestyle-related diseases [2]. Mushrooms have proven to be one of the most important sources of bioactive compounds such as flavonoids, alkaloids, terpenoids, and sterols, with intriguing structures [2]. In continuation of our studies on the chemical constituents from mushrooms, 44 new compounds have been obtained and characterized from 18 species of mushrooms, namely, Amanita virgineoides, Grifola frondosa, Hericium erinaceum, Hypsizygus marmoreus, Lactarius piperatus, Lentinula edodes, Lyophyllum connatum, Naematoloma sublateritium, Omphalia lapidescens, Panellus serotinus, Pholiota nameko, Pleurotus eryngii, Polyporus umbellatus, Russula delica, R. sanguinea, Sarcodon aspratus, Tricholoma matsutake, and T. portentosum.

In this chapter, we described our studies on the isolation and structure elucidation of the new terpenoids and sterols from the above mushrooms. This chapter also presents a brief overview of the subject, highlighting some major contributions during the past 15 years, and not intended to be a comprehensive review.

Sesquiterpenoids

Lactarane-Type Sesquiterpenoids

The family Russulaceae is one of the largest in the subdivision Basidiomycotina in Whittaker's Kingdom of Fungi [3] and the representative genera are Lactarius and Russula. Although secondary metabolites occurring in the fruiting bodies of Lactarius species have been well investigated [4], the Russula mushrooms have received less attention, notwithstanding the larger number of existing species [5].

Three new lactarane-type sesquiterpenoids, sangusulactones A–C (1–3) were isolated from the methanol extract of the fruiting bodies of R. sanguinea (Fig. 1.1) [6]. The structures of the new compounds were established by spectroscopic methods, especially 2D-COSY, NMR and MS analyses.

Figure 1.1Structures of lactarane-type sesquiterpenoids 1–11.

The molecular formula of 1 was determined to be C15H22O4 by high-resolution electron ionization mass spectrometry (HREIMS). The 1H- and 13C-NMR spectra showed signals due to a tertiary methyl group, a secondary methyl group, four methylenes, five methines, a trisubstituted double bond and a carbonyl group. These NMR data were very similar to those of blennin A (4) (Fig. 1.1) [7] with the exception that the resonances due to one of the methyl groups at C-11 in 4 were replaced by hydroxymethyl group signals in 1. The hydroxymethyl group was assigned to C-14 on the basis of the 1H-detected heteronuclear multiple bond connectivity (HMBC) correlations of 2H-14 with C-1, C-10, and C-15. The relative configuration of 1 was determined from the nuclear Overhauser effect correlation spectroscopy (NOESY) spectrum, in which cross peaks were observed between H-2 and H-9, and H-7 and H-9, implying a cis-junction for the A/B rings, and that H-2, H-7, and H-9 occurred on the same face (ß) of the ring system (Fig. 1.2). The NOESY cross peak observed between H-3 and H-8 suggested that the methyl group at C-3 and the hydroxyl group at C-8 both are of ß and ß orientation, respectively (Fig. 1.2). The absolute configuration of 1 was elucidated by applying the helicity rule [8]. The circular dichroism (CD) spectrum of 1 showed a negative Cotton effect by the left-handed (M) helicity of the C(3)– C(4)=C(6) bond system at 205.1 nm (-1.02). Thus, the absolute configuration at C-3 was assigned as R, indicating the 2R, 7R, 8S, 9R, and 11S configurations (Fig. 1.2).

Figure 1.2NOEs (full-line arrows) and M helicity of the C(3)– C(4) = C(6) bond system in lactarane-type sesquiterpenoid 1.

The 13C-NMR...