The Neutral Constituents of the Cactus Lophocereus schottii. The Structure of Lophenol--4α-Methyl-Δ<sup>7</sup>-cholesten-3β-ol--A Link in Sterol Biogenesis<sup>1-3</sup>

Djerassi, Carl; Krakower, Gerald W.; Lemin, A. J.; Liu, Liang H.; Mills, John; Villotti, R.

doi:10.1021/ja01556a031

Cited by 70 publications

(6 citation statements)

References 10 publications

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“…The key step in the synthesis is the PtO 2 -catalyzed isomerization of the 7(8)-double bond of lophenol ( Scheme 1 , part 1) to the more stable 8 (14) isomer (Scheme 1, part 2) (22).…”

Section: Synthesis Of 4-␣ -Methyl-5-␣ -Cholest-8(14)-en-3 ␤ -Olmentioning

confidence: 99%

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Sterol effects and sites of sterol accumulation in Caenorhabditis elegans

Merris

Wadsworth

Khamrai

et al. 2003

Journal of Lipid Research

118

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Caenorhabditis elegans requires sterol, usually supplied as cholesterol, but this is enzymatically modified, and different sterols can substitute. Sterol deprivation decreased brood size and adult growth in the first generation, and completely, reversibly, arrested growth as larvae in the second. After one generation of sterol deprivation, 10 ng/ml cholesterol allowed delayed laying of a few eggs, but full growth required 300 ng/ml. C. elegans synthesizes two unusual 4 ␣ -methyl sterols (4MSs), but each 4MS supported only limited growth as the sole sterol. However, addition of only 10 ng of cholesterol to 1,000 ng of 4MS restored full growth and egg-laying, suggesting that both a 4MS and an unmethylated sterol are required for development. Filipin stained sterols in only a few specific cells: the excretory gland cell, two amphid socket cells, two phasmid socket cells and, in males, spicule socket cells. Sterols were also present in the pharynx and in the intestine of feeding animals in a proximal-to-distal gradient.This non-random sterol distribution, the low concentration requirements, and the effects of 4MSs argues that sterols are unlikely to be used for bulk structural modification of cell membranes, but may be required as hormone precursors and/or developmental effectors. Dietary sterol is required by Caenorhabditis elegans (1, 2) because, like insects, C. elegans is incapable of synthesizing the four-ring sterol nucleus, but its functions remain largely unknown. The existence of sterol-based hormones in C. elegans has recently been suggested, but no hormone has yet been identified (3, 4). Cholesterol is known to be extensively metabolized by C. elegans to form several other sterols, including two unusual 4 ␣ -methyl sterols (4MSs), which are present in substantial amounts (5-8, 9). These sterols might thus be functional, instead of or in addition to cholesterol itself.Insects resemble these nematodes in requiring sterols but being unable to synthesize them. Two functions for cholesterol are known in insects: as the metabolic precursor of the molting hormone ecdysone (10), and as the moiety required for activation by covalent attachment to the morphogen protein hedgehog (11). Insect cells, unlike vertebrate cells, grow normally under sterol-free conditions, and thus do not need cholesterol in their plasma membranes (12)(13)(14).We have now characterized the sterol requirements of C. elegans in some detail. Conditions for stringent sterol deprivation were developed, and the consequences are described. The use of these conditions allowed us to investigate minimum cholesterol requirements, and the ability of other sterols to substitute. Partial and synergistic effects were found, suggesting that different sterols have diverse effects mediated by several pathways. The accumulation of sterol in the intestinal tract and in a few specific cells in C. elegans was also demonstrated by filipin staining, which stains all 3 ␤ -hydroxy sterols.These observations provide a basis for a comprehensive study of ster...

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“…The key step in the synthesis is the PtO 2 -catalyzed isomerization of the 7(8)-double bond of lophenol ( Scheme 1 , part 1) to the more stable 8 (14) isomer (Scheme 1, part 2) (22).…”

Section: Synthesis Of 4-␣ -Methyl-5-␣ -Cholest-8(14)-en-3 ␤ -Olmentioning

confidence: 99%

“…Egg-laying thus occurred at cholesterol levels that profoundly retarded overall growth, suggesting that these properties are independently regulated by sterols. (22), they have no known function in any organism.…”

Section: Quantitation Of the Cholesterol Requirementmentioning

confidence: 99%

Sterol effects and sites of sterol accumulation in Caenorhabditis elegans

Merris

Wadsworth

Khamrai

et al. 2003

Journal of Lipid Research

118

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“…Although many investigators have contributed to our knowledge of the chemistry of columnar cacti, two individuals stand out: Carl Djerassi and Henry Kircher. Djerassi's work in the 1950s and 60s includes some of the original chemical descriptions of cactus alkaloids and triterpenes (Djerassi and Lippman, 1955;Djerassi et al, 1953aDjerassi et al, , b, 1954aDjerassi et al, , b, 1955Djerassi et al, , 1957Djerassi et al, , 1958Djerassi et al, , 1962. Kircher was a collaborator of Bill Heed and was specifically involved in the chemistry of the cactus-microorganism-Drosophila model system from its inception in the early 1960s (Kircher, 1977(Kircher, , 1980(Kircher, , 1982Kircher and Bird, 1982).…”

Section: Allelochemistry Of Columnar Cactimentioning

confidence: 99%

Chemical Interactions in the Cactus-Microorganism-Drosophila Model System of the Sonoran Desert1

Fogleman

Danielson

2001

American Zoologist

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SYNOPSIS. The Cactus-Microorganism-Drosophila Model System of the Sonoran Desert represents an excellent paradigm of the role of chemistry in plant-animal interactions. In this system, four species of endemic Drosophila feed and reproduce in necrotic tissue of five species of columnar cacti. Studies over the past 35 yr have characterized a myriad of interactions between the three major components of the model system. The cacti contain a variety of allelochemicals which are primarily responsible for the highly specific pattern of host plant utilization exhibited by the desert Drosophila. Plant chemistry, through its effect on the microbially produced volatile patterns, is further involved in host specificity because the flies use the volatile pattern to cue in on necroses in the appropriate species of cactus. The metabolic activities of microorganisms (bacteria and yeasts) living in the necrosis can affect the substrate chemistry in both positive and negative ways (i.e., acting to increase or to decrease the toxicity of the substrate). Finally, cactus chemistry may affect drosophilid mating behavior since larval rearing substrate has been shown to influence adult hydrocarbon epicuticular composition. In D. mojavensis, adult hydrocarbon profile has been implicated as a determinant of mate choice leading to premating isolation between geographically isolated populations that use chemically different cactus substrates. Current research is focused on the evolution and regulation of genes whose products (cytochrome P450 enzymes) are involved in the specific insect-host plant relationships which exist between the Drosophila species and the cactus species.There are many reasons why investigators choose to focus their research efforts on what are referred to as ''model systems.'' Typically included among these would be the idea that model systems are easier to study because they are less complex than other scientific situations. At the same time, model systems should be representative of more complex, natural systems so that information that is obtained from their study is broadly applicable. For almost a century, the fruit fly, Drosophila melanogaster, has served as a model organism for the study of genetics. As a genetic paradigm, Drosophila is more tractable to scientific investigation than most organisms and has provided important insights into a wide variety of human maladies from alcohol abuse to neurological brain disorders (Bellen, 1998). Similarly, the interrelationships of the columnar cacti and the cactophilic Drosophila species of the Sonoran Desert have, for the past 35 yr, provided an excellent model system with which to study relevant questions in evolution, ecological genetics, and chemical ecology. The intent of this article is to briefly review and characterize the chemical interactions between the plants (cacti) and animals (Drosophila) of this model system, and, in addition, provide some thoughts on possible future directions for integrative approaches in this research area.

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“…THIQ alkaloids with an isobutyl group at C-1 (lophocereine) have been isolated from L. schotti, a desert cactus [49,50]. No other naturally-occurring THIQs with an aliphatic group at the C-1 position have been identified.…”

Section: Putative Pictet-spenglerase From Lophocereus Schottiimentioning

confidence: 99%

Pictet–Spenglerases in alkaloid biosynthesis: Future applications in biocatalysis

Roddan

Ward

Keep

et al. 2020

Current Opinion in Chemical Biology

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Pictet-Spenglerases provide a key role in the biosynthesis of many biologically-active alkaloids. There is increasing use of these biocatalysts as an alternative to traditional organic synthetic methods as they provide stereoselective and regioselective control under mild conditions. Products from these enzymes also contain privileged drug scaffolds (such as tetrahydroisoquinoline or b-carboline moieties), so there is interest in the characterisation and use of these enzymes as versatile biocatalysts to synthesize analogues of the corresponding natural products for drug discovery. This review discusses all known Pictet-Spenglerase enzymes and their applications as biocatalysts.

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The Neutral Constituents of the Cactus Lophocereus schottii. The Structure of Lophenol--4α-Methyl-Δ⁷-cholesten-3β-ol--A Link in Sterol Biogenesis^1-3

Cited by 70 publications

References 10 publications

Sterol effects and sites of sterol accumulation in Caenorhabditis elegans

Sterol effects and sites of sterol accumulation in Caenorhabditis elegans

Chemical Interactions in the Cactus-Microorganism-Drosophila Model System of the Sonoran Desert1

Pictet–Spenglerases in alkaloid biosynthesis: Future applications in biocatalysis

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The Neutral Constituents of the Cactus Lophocereus schottii. The Structure of Lophenol--4α-Methyl-Δ7-cholesten-3β-ol--A Link in Sterol Biogenesis1-3

Cited by 70 publications

References 10 publications

Sterol effects and sites of sterol accumulation in Caenorhabditis elegans

Sterol effects and sites of sterol accumulation in Caenorhabditis elegans

Chemical Interactions in the Cactus-Microorganism-Drosophila Model System of the Sonoran Desert1

Pictet–Spenglerases in alkaloid biosynthesis: Future applications in biocatalysis

Contact Info

Product

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About

The Neutral Constituents of the Cactus Lophocereus schottii. The Structure of Lophenol--4α-Methyl-Δ⁷-cholesten-3β-ol--A Link in Sterol Biogenesis^1-3