Synthesis Of Triterpenes Research Articles

Biochemical analysis of a multifunctional cytochrome P450 (CYP51) enzyme required for synthesis of antimicrobial triterpenes in plants

Members of the cytochromes P450 superfamily (P450s) catalyze a huge variety of oxidation reactions in microbes and higher organisms. Most P450 families are highly divergent, but in contrast the cytochrome P450 14α-sterol demethylase (CYP51) family is one of the most ancient and conserved, catalyzing sterol 14α-demethylase reactions required for essential sterol synthesis across the fungal, animal, and plant kingdoms. Oats (Avena spp.) produce antimicrobial compounds, avenacins, that provide protection against disease. Avenacins are synthesized from the simple triterpene, β-amyrin. Previously we identified a gene encoding a member of the CYP51 family of cytochromes P450, AsCyp51H10 (also known as Saponin-deficient 2, Sad2), that is required for avenacin synthesis in a forward screen for avenacin-deficient oat mutants. sad2 mutants accumulate β-amyrin, suggesting that they are blocked early in the pathway. Here, using a transient plant expression system, we show that AsCYP51H10 is a multifunctional P450 capable of modifying both the C and D rings of the pentacyclic triterpene scaffold to give 12,13β-epoxy-3β,16β-dihydroxy-oleanane (12,13β-epoxy-16β-hydroxy-β-amyrin). Molecular modeling and docking experiments indicate that C16 hydroxylation is likely to precede C12,13 epoxidation. Our computational modeling, in combination with analysis of a suite of sad2 mutants, provides insights into the unusual catalytic behavior of AsCYP51H10 and its active site mutants. Fungal bioassays show that the C12,13 epoxy group is an important determinant of antifungal activity. Accordingly, the oat AsCYP51H10 enzyme has been recruited from primary metabolism and has acquired a different function compared to other characterized members of the plant CYP51 family--as a multifunctional stereo- and regio-specific hydroxylase in plant specialized metabolism.

Overexpression of the Trichoderma brevicompactum tri5 Gene: Effect on the Expression of the Trichodermin Biosynthetic Genes and on Tomato Seedlings

Trichoderma brevicompactum IBT 40841 produces trichodermin, a trichothecene-type toxin that shares most of the steps of its biosynthesis with harzianum A, another trichothecene produced by several Trichoderma species. The first specific step in the trichothecene biosynthesis is carried out by a terpene cylcase, trichodiene synthase, that catalyzes the conversion of farnesyl pyrophosphate to trichodiene and that is encoded by the tri5 gene. Overexpression of tri5 resulted in increased levels of trichodermin production, but also in an increase in tyrosol and hydroxytyrosol production, two antioxidant compounds that may play a regulatory role in trichothecene biosynthesis, and also in a higher expression of three trichothecene genes, tri4, tri6 and tri10, and of the erg1 gene, which participates in the synthesis of triterpenes. The effect of tri5 overexpression on tomato seedling disease response was also studied.

ChemInform Abstract: Synthesis, Biology and Clinical Significance of Pentacyclic Triterpenes: A Multi‐Target Approach to Prevention and Treatment of Metabolic and Vascular Diseases

AbstractReview: 335 refs.

Synthesis, biology and clinical significance of pentacyclic triterpenes: a multi-target approach to prevention and treatment of metabolic and vascular diseases

This review (with 335 references cited) is devoted to pentacyclic triterpenes. The total synthesis, semi-synthesis, structural modification, and metabolic behavior of naturally occurring pentacyclic triterpenes are described. We also cover the in vivo evidence, mechanistic studies, and clinical significance of pentacyclic triterpenes as multi-target therapeutic agents for the prevention and treatment of metabolic and vascular diseases.

ChemInform Abstract: An Exceptionally Short and Simple Enantioselective Total Synthesis of Pentacyclic Triterpenes of the β-Amyrin Family.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Efficient synthesis of morolic acid and related triterpenes starting from betulin

Morolic acid ( 1) is a naturally occurring pentacyclic triterpene whose derivatives exhibit promising anti-HIV and other biological activities. An efficient synthesis of 1 has been accomplished in 11 steps with a total yield of 24% starting from betulin. Some related natural triterpenes including moradiol ( 4), acridocarpusic acid D ( 5), acridocarpusic acid E ( 6), and moronic aldehyde ( 7) have also been synthesized. Biological assay results showed that 1, 5, and 6 exhibited moderate inhibitory activity against glycogen phosphorylase.

Enzymatic synthesis of cyclic triterpenes

This review covers recent advances in the chemistry and enzymology of squalene cyclase and oxidosqualene cyclase. The enzymatic cyclizations of squalene and oxidosqualene are the most remarkable steps in the biosynthesis of sterols and triterpenes. The polyenes are converted to various polycyclic triterpenes by different enzyme systems employing only small modification of the active-site. Recent crystallographic and structure-based mutagenesis studies as well as utilization of chemically synthesized active-site probes have begun to reveal intimate structural details of the enzyme-templated cyclization reactions. 126 References are cited.

Reductive Coupling of Terpenic Allylic Halides Catalyzed by Cp2TiCl: A Short and Efficient Asymmetric Synthesis of Onocerane Triterpenes

[reaction: see text] Titanocene chloride catalyzes the regioselective alpha,alpha'-homocoupling of terpenic allylic halides. This process has been employed in the short and effective synthesis of terpenoids such as beta-onoceradiene (1), beta-onocerin (2), and squalene (3). Evidence is presented for eta1-allyltitanium species being involved in the coupling.

Unravelling triterpene glycoside synthesis in plants: phytochemistry and functional genomics join forces

Plants produce a vast array of secondary metabolites, many of which have important ecological functions. The ability to perform in vivo combinatorial chemistry by mixing, matching and evolving the genes required for different secondary metabolite biosynthetic pathways is likely to have been critical for survival and diversifica tion of the members of the plant kingdom. The terpenes form one of the largest and most diverse groups of plant natural products. This group of compounds includes sterols and triterpenes, which can accumulate as glyco side conjugates (saponins) in substantial quantities in plants. Saponins have a diverse range of properties, includ ing antimicrobial, anti-insect and allelopathic activity (Hostettmann and Marston 1995; Oleszek and Marston 2000). They also have pharmacological applications, for example as anti-cancer agents (Hanausek et al. 2001). This review is concerned with recent developments in our understanding of the synthesis of the triterpene glycoside family of saponins (Fig. la). Triterpene sapo nins occur predominantly in dicotyledonous plants (Hostettmann and Marston 1995). Monocots appear to lack these compounds with the notable exception of oats, which produce defence-related triterpenoid sapo nins known as avenacins in the roots (Osbourn 2003). In higher plants, 2,3-oxidosqualene is a common precursor in the synthesis of both triterpenes and sterols. The first committed step in sterol biosynthesis in plants is the conversion of 2,3-oxidosqualene to cycloartenol, catalysed by the oxidosqualene cyclase cycloartenol synthase. Synthesis of triterpenes involves cyclisation of 2,3-oxidosqualene into various triterpene skeletons,

Synthesis of a pentacyclic lactone related to quinovaic acid and emmolactone using an anionic polycyclization strategy

In an effort to discover a versatile and convergent synthesis of pentacylic triterpenes, we have synthesized a tetracyclic enone via a highly stereocontrolled cycloaddition between a Nazarov precursor and a cyclohexenone followed by an aldol condensation. Introduction of a C14 nitrile was made by hydrocyanation on a protected derivative of this tetracyclic enone. Reduction and subsequent hydrolysis of the latter intermediate concluded this expedient synthesis of a pentacyclic lactone.

Molecular cloning and expression in yeast of 2,3-oxidosqualene-triterpenoid cyclases from Arabidopsis thaliana.

A vast array of triterpenes are found in living organisms in addition to lanosterol and cycloartenol, which are involved in sterol biosynthesis in non-photosynthetic and photosynthetic eukaryotes respectively. The chemical structure of these triterpenes is determined by a single step catalysed by 2,3-oxidosqualene-triterpene cyclases. The present study describes cloning and functional expression in yeast of several OS-triterpene cyclases. Three Arabidopsis thaliana cDNAs encoding proteins (ATLUP1, ATLUP2, ATPEN1) 57%, 58% and 49% identical to cycloartenol synthase from the same plant were isolated. Expression of these cDNAs in yeast showed that the recombinant proteins catalyse the synthesis of various pentacyclic triterpenes. Whereas ATLUP1 is essentially involved in the synthesis of lupeol, ATLUP2 catalyses the production of lupeol, beta- and alpha-amyrin (in a 15:55:30 ratio). ATLUP2 is therefore a typical multifunctional enzyme. Under the same conditions, ATPEN1 did not lead to any product. Systematic sequencing of the Arabidopsis genome has led to genomic sequences encoding proteins identical to the above triterpene synthases. ATLUPI and ATLUP2 are representative of a small subfamily (A) of at least five genes, whereas ATPEN1 is representative of a subfamily (B) of at least seven genes. The number of introns is characteristic of each subfamily. Whereas genes of family A possess 17 exons and 16 introns, genes of the subfamily B contain 14 exons and 13 introns. The size of each exon is remarkably conserved within each subfamily whereas that of each intron appears to be highly variable. Organization of the genes, sequences and functions of the deduced proteins are discussed in evolutionary terms.

Intramolecular [3 + 2]-Hetero-Annulation of Allylsilanes with 1,3-Cyclohexanediones and its Application in the Synthesis of Hexacyclic Hopane Triterpenes

Intramolecular [3 + 2]-Hetero-Annulation of Allylsilanes with 1,3-Cyclohexanediones and its Application in the Synthesis of Hexacyclic Hopane Triterpenes

An Exceptionally Short and Simple Enantioselective Total Synthesis of Pentacyclic Triterpenes of the β-Amyrin Family

A new and very direct enantioselective total synthesis of members of the β-amyrin family of pentacyclic triterpenes has been developed starting with acylsilane 5, 2-propenyllithium, and cyclohexenylmethyl bromide 6, which were assembled to form tetraene 7. Cationic cyclization of 7 and silylation afforded 8, which after vinyl triflate formation was cyclized via a Cu(I) intermediate (Scheme 2) to form the TBS ether of aegiceradienol 10, a versatile intermediate that is readily converted into natural β-amyrins such as β-amyrin (1) and oleanolic acid (2). The C(14)-diastereomer (13) of aegiceradienol was also synthesized from the C(14)-diastereomer of 8 using an intramolecular Stille reaction for the closure of ring D (Scheme 4).

Studies towards the total synthesis of pentacyclic triterpenes of the arborane and fernane family

Stereo and regrochemcal variations in conjugate addition reactions leading to isoarborinal and fernenol-Hke interpenes via a five-step protccol are described. The Gngnard addition on 9, 10, 15, 18 served lo establish the relative stereoehemicul details.

Mobilization of Reserves and Synthesis of Sterols and Triterpenes in Seedlings of Two Canarian Euphorbia Species

Mobilization of Reserves and Synthesis of Sterols and Triterpenes in Seedlings of Two Canarian Euphorbia Species

ChemInform Abstract: Approaches to the Synthesis of Triterpenes. Part 9. Diethylaluminum Ethoxide as a Reagent for the Intramolecular Aldol Condensation.

ChemInformVolume 19, Issue 16 Preparative Organic Chemistry ChemInform Abstract: Approaches to the Synthesis of Triterpenes. Part 9. Diethylaluminum Ethoxide as a Reagent for the Intramolecular Aldol Condensation. J. W. APSIMON, J. W. APSIMON Ottawa-Carleton Chem. Inst., Carleton Campus, Carleton Univ., Ottawa, Ontario, Canada K1S 5B6Search for more papers by this authorR. F. LAWUYI, R. F. LAWUYI Ottawa-Carleton Chem. Inst., Carleton Campus, Carleton Univ., Ottawa, Ontario, Canada K1S 5B6Search for more papers by this author J. W. APSIMON, J. W. APSIMON Ottawa-Carleton Chem. Inst., Carleton Campus, Carleton Univ., Ottawa, Ontario, Canada K1S 5B6Search for more papers by this authorR. F. LAWUYI, R. F. LAWUYI Ottawa-Carleton Chem. Inst., Carleton Campus, Carleton Univ., Ottawa, Ontario, Canada K1S 5B6Search for more papers by this author First published: April 19, 1988 https://doi.org/10.1002/chin.198816086Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume19, Issue16April 19, 1988 RelatedInformation

ChemInform Abstract: A Novel Stereospecific Synthesis of 22‐Hydroxylated Triterpenes and Steroids: Syntheses of (22R)‐Hydroxyanosterol and (22R)‐Hydroxydesmosterol.

ChemInformVolume 19, Issue 1 Natural Products ChemInform Abstract: A Novel Stereospecific Synthesis of 22-Hydroxylated Triterpenes and Steroids: Syntheses of (22R)-Hydroxyanosterol and (22R)-Hydroxydesmosterol. A. AMANN, A. AMANN Shanghai Inst. Org. Chem., Acad. Sin., Shanghai, ChinaSearch for more papers by this authorG. OURISSON, G. OURISSON Shanghai Inst. Org. Chem., Acad. Sin., Shanghai, ChinaSearch for more papers by this authorB. LUU, B. LUU Shanghai Inst. Org. Chem., Acad. Sin., Shanghai, ChinaSearch for more papers by this author A. AMANN, A. AMANN Shanghai Inst. Org. Chem., Acad. Sin., Shanghai, ChinaSearch for more papers by this authorG. OURISSON, G. OURISSON Shanghai Inst. Org. Chem., Acad. Sin., Shanghai, ChinaSearch for more papers by this authorB. LUU, B. LUU Shanghai Inst. Org. Chem., Acad. Sin., Shanghai, ChinaSearch for more papers by this author First published: January 5, 1988 https://doi.org/10.1002/chin.198801321AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume19, Issue1January 5, 1988 RelatedInformation

Approaches to the Synthesis of Triterpenes. IX. Diethylaluminum Ethoxide as a Reagent for the Intramolecular Aldol Condensation

Abstract The use of diethylaluminum ethoxide as a reagent for some extremely hindered intramolecular aldol condensations is described, providing substrates of used in the synthesis of pentacyclic triterpenes.

Mobilisation of reserves and the earliest synthesis of sterols and latex triterpenes during germination and early seedling growth of Euphorbia lathyris

Seedlings of Euphorbia lathyris L. were grown in the dark at 25°C. Levels of amino acids, sugars and soluble phosphate in the endosperm increased upon germination after 4 days of imbibition, while the amounts of mineral reserves Mg2+ and K+ started decreasing. Ca2+ was not translocated from the endosperm to the seedling. Maximum values for amino acids were found on day 7, and the highest amounts of sugars were present on day 10. The endosperm was completely depleted by day 12.Before germination (days 1–3) a low level of sterol synthesis in the embryo was detected with labeled sucrose and serine and to a lesser extent with labeled pyruvate. The label of [2‐14C]‐mevalonate proceeded exclusively to squalene. Laticifers started the synthesis of their triterpenes upon germination (day 4), using sucrose as a main substrate. A concurrent increase of sterol synthesis outside the laticifers was traced with labeled serine. Radioactive triterpenes, 4 α‐methylsterols and sterols were detected in growing seedlings after [14C]‐mevalonate uptake, but most of its label accumulated in squalene. The use of labeled mevalonate in sterol synthesis in growing seedlings is discussed.

Total synthesis of tetracyclic triterpenes 2 an efficient synthesis of 1,4-dimethoxy-14α-methyl-11-oxoestra-1,3,5(10)-triene

Diels-Alder cycloaddition of 1,4-benzoquinone with diene 2 gave the α-endo adduct 6 in good yield. Acid catalyzed aromatization of 6 was controlled, so as to give either the unconjugated hydroquinone derivative 7 or the conjugated Δ 9(11) isomer 9. The dimethoxy derivative 12 gave acid-labile epoxides 17 and 18, which were assigned the β and α configuration respectively on the strength of their characteristic 1 Hnmr spectra. Acid-catalyzed rearrangement of these epoxides yielded the stereoisomeric 11-ketones 19 and 20. A comparison of 1Hnmr data for 19 and 20 with previously-reported analogs in which either the 11-carbonyl function or the 14α-methyl group are absent led to assignment of the 9β-conflguratlon (BC-cis) to the former and the 9α-configuratlon to 20. X-ray analysis has confirmed the configurations of 19 and 20. Significant distortion of ring C Is found In both isomers, and is attributed to dipole repulsion between the 1-methoxyl substituent and the carbonyl function. The common enolate anion derived from these ketones gave only 0-methylatlon, and on protonation gave a mixture of enol 21 and 19. Dehydrogenation reactions of 7 and its bis-methyl ether 10 yielded naphthoquinone derivatives 13 and 14, and the dimethoxy naphthalene 15.