Steroid alkaloids biosynthesis

An alternative sequence of functionalization and ring-closure in steroidal alkaloid biosynthesis has been reported, proceeding via 26-amino-furostanols for, e.g., the biosynthesis of solasodine. In the light of the new evidence it has been concluded that such a pathway must be a minor one. ... 

Pollinastanol (9p,19-cyclopropane-/C27-type), 5a-cholest-8-en-3P-ol, and isofucosterol (substituent at C-24 =C-CH3 ci g) were accumulated in discs of potato tubers when treated with synthetic inhibitors of the steroidal alkaloid biosynthesis (Bergenstraahle et al. 1996). 

Saponins are glycosylated secondary metabolites that are widely distributed in the Plant Kingdom.3,4 They are a diverse and chemically complex family of compounds that can be divided into three major groups depending on the structure of the aglycone, which may be a steroid, a steroidal alkaloid, or a triterpenoid. These molecules have been proposed to contribute to plant defense.3 6 Saponins are also exploited as drugs and medicines and for a variety of other purposes.4 Despite the considerable commercial interest in this important group of natural products, little is known about their biosynthesis. This is due in part to the complexity of the molecules, and also to the lack of pathway intermediates for biochemical studies. 

McCue, K. F., Shepherd, L. V. T., Allen, P. V, Maccree, M. M., Rockhold, D. R., Corsini, D. L., Davies, H. V, Belknap, W. R. (2005). Metabolic compensation of steroidal glycoalkaloid biosynthesis in transgenic potato tubers using reverse genetics to confirm the in vivo enzyme function of a steroidal alkaloid galactosyltransferase. Plant science, 168, 267-273. 

B-79MI10405)) and to attempt to present a comprehensive list would be a mammoth task. A number of general introductory texts are available which provide an overview of the subject and an entrance to the more specialist literature (e.g. B-78MI10401, B-78MI10402, B-81MI10402, B-81MI10403). A more comprehensive view of the literature from 1971 to 1978 is provided by The Royal Society of Chemistry series Biosynthesis (Specialist Periodic Reports), volumes 1 to 6, and by various chapters of the companion series Terpenoids and Steroids , Alkaloids and Peptides and Proteins . 

The biosynthesis of alkaloids has been extensively studied, and although for a time it was thought that alkaloids arose primarily from amino acid precursors, strong evidence now is available that ethanoate also is involved. The mode of alkaloid biosynthesis is not yet as well understood as that of the terpenes and steroids. One experimental problem is the difficulty of feeding suitably labeled precursors to plants. 

This chapter discusses some of the more important natural products terpenes, steroids, alkaloids, fats, and prostaglandins. (Fats are primary natural products, but it is convenient to include them in this chapter.) The structures and various aspects of their biosynthesis and chemical reactions are presented in subsequent sections. Because entire books have been written on each of these groups of compounds, the coverage here is necessarily incomplete. However, the intent is to present some of the flavor of their chemistry. Many other classes of naturally occurring organic compounds are not included for reasons of space. 

Further exploration125 of the stereochemistry associated with modification of the steroidal side-chain into that of steroidal alkaloids such as solanidine (139) and tomatidine (140) has revealed that on formation of the furan ring in (140) tritium in the 16/8-configuration of cholesterol [as (143)] is retained but appears now in the 16a-configuration. Retention of the tritium excludes a C-16-oxo-intermediate, and the fact that an inversion of configuration is observed excludes hydroxylation with normal retention of configuration. Examination of the fate of the cholesterol 16/S-proton on incorporation into solanidine (139) revealed that during solanidine biosynthesis this proton is lost. 

Steroidal Alkaloids.—In the biosynthesis of alkaloids such as solasodine (128), from cholesterol (129), it appears that the cholesterol side-chain is first functionalized at C-26 with the introduction of a hydroxy-group (cf. Vol. 8, p. 28 Vol. 7, p. 32). The 26-amino-compound, (25i )-26-aminocholesterol (130), has been found to act as a significant precursor for solasodine (128) in Solarium laciniatum, whereas (25i )-26-aminocholest-5-ene-3/ ,16/ -diol (131) was poorly utilized.105 This indicates that replacement of the hydroxy-group at C-26 by an amino-group may occur before further oxygenation elsewhere in the steroid nucleus (particularly at C-16). It may also be concluded from this and other evidence (cf. Vol. 9, p. 27) that oxidation at C-22 precedes hydroxylation at C-16. 

Plant sterols are products of primary metabolism, but they may also be regarded as direct precursors of many secondary plant metabolites, such as the cardiac glycosides, saponins and steroid alkaloids. All of the compounds mentioned share the same basic skeleton therefore, the accumulation of a particular compound can only be achieved if (1) enzymes with a high degree of substrate specificity are involved in their biosynthesis, (2) metabolites can be channelled efficiently to the respective pathways and (3) products can be transported, sequestered and/or stored in specific compartments. 

Steroidal and Terpenoid Alkaloids.—Following upon earlier work on the biosynthesis of steroidal alkaloids it has been shown that (255)-5a -cholestan-3/8,26-diol (159), but not the corresponding furostan derivative (160), is a precursor for tomatidine (162) in Lycopersicon pimpinellifolium [This contrasts with the observation that the (255)-sapogenin, neotigogenin (163), was labelled by both precursors in these experiments.] If these results are taken together with the observation that... 

It is now apparent, however, that the Specialist Periodical Reports on "The Alkaloids", "Biosynthesis", "Terpenoids and Steroids" and "Aliphatic and Related Natural Product Chemistry" are not financially viable in their present book format and in 1984 they are to be replaced by a review journal to be called "Natural Product Reports". The new journal is to be published every two months and will continue to give comprehensive annual surveys of the four areas of natural product research additional articles on subjects not covered by existing Specialist Periodical Reports on topics such as chemotaxonom.y and enzymology and on advances in physical techniques will be included periodically and author and subject indices are to be provided. The flexible production timetable should ensure more rapid publication of manuscripts compared with S.P.R. s. In order to maintain continuity the S.P.R. Senior Reporters are members of the Editorial Board of Natural Products Reports and in the case of the alkaloid chapters it is expected that the present authors will contribute to the Journal. We all hope that the support we have received over the years from alkaloid chemists will be extended to this new and exciting venture. As always comments and suggestions will be much appreciated. 

Steroidal Alkaloids.—Further study on the biosynthesis of Veratrum alkaloids has been published (for earlier work see refs. 224 and 225). The results obtained with dormant rhizome slices of V. grandiflorum were that (a) labelled verazine (207) gave rise to radioactive rubijervine (211) and hakurirodine (210), a new alkaloid isolated from dormant tuber slices, and (b) labelled etioline (208), a probable progenitor of solanidine (209), was not incorporated into either alkaloid. It was concluded that the biosynthetic pathway to solanidine (209) branches from that to rubijervine (211) at verazine (207) (see Scheme 25). 

Study of the biosynthesis of ergot and steroidal alkaloids continues. The biosynthesis of the necic acid components of the pyrrolizidine alkaloids has been elucidated,and attention has turned to the biosynthesis of the pyrrolizidine nucleus, which is largely unknown (see this Report, p. 13). 

Biosynthesis These alkaloids are formed by the usual plant steroid biosynthetic pathway via cycloartenol and cholesterol. The Solanum steroid alkaloids and procevine (22/J,255)-18,22,26-nitrilocholest-5-en-3/S-ol, CAS [468-24-6] also present in Liliaceae are important intermediates in these processes and furnish all the other types of compounds by carbon skeleton rearrangement and ring closure reactions. ... 

Salamander contains lot of alkaloids. Samandarine (C19H31NO2) and samandarone (C19H29NO2) are two major alkaloids from European fire salamander (Salamandra salamandra terrestris). These alkaloids are secreted from both the skin and internal organs of the salamander. Other alkaloids are samandaridine, samandinine, cycloneosamandione, samandenone, and samanine. They are steroidal alkaloids and their precursor in the biosynthesis pathway is considered to be cholesterol. Samanine is possible to synthesize synthetically. " ... 

Steroid and Triterpenoid Alkaloids Solanum Alkaloids Biosynthesis... 

The above-mentioned types of Solanum alkaloids are derived from the same pathways as most other steroids in plants. For more information on the formation of the various precursors involved, see Chapters 23 and 24. The biosynthesis and metabolism of the C27 sapogenins and alkaloids are closely related (Ripperger and Schreiber, 1981 Gross et al, 1985). Acetate and mevalonate are incorporated into all types of steroid alkaloids. 

C. is biosynthesized from acetyl-CoA via the tri-terpene lanosterol (see Steroids, Figs. 7 8) and zymosterol. In turn, it is a key intermediate in the biosynthesis of many other steroids, including steroid hormones, steroid sapogenins and steroid alkaloids. 

The biochemistry, especially the biosynthesis, of plant steroids in general and of steroid alkaloids in particular, has been reviewed occasionally in the last decade for instance, see Heftmann (276-278), Schreiber (55, 279), Schiitte (280, 281), and Roddick (56). 

In other investigations, radioactivdy labeled (25/l)-26-aminocholesterol (306) administered to S. laciniatum was incorporated to a high extent into solasodine (1), whereas the corresponding 16/S-hydroxy derivatives (25/ )-26-aminocholest-5-ene-3/ ,16jS-diol and its 7V-acetyl derivative (306) show only small incorporations (307). These results suggested that in the biosynthesis of C27 steroid alkaloids the introduction of nitrogen occurs imme-... 

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