Isolation, structure, and synthesis of combretastatin A-2, A-3, and B-2

1987 ◽  
Vol 65 (10) ◽  
pp. 2390-2396 ◽  
Author(s):  
George R. Pettit ◽  
Sheo Bux Singh
Keyword(s):  
South African ◽  
Wittig Reaction ◽  
Lymphocytic Leukemia ◽  
Tubulin Polymerization ◽  
Synthetic Route ◽  
Methyl Gallate ◽  
Total Syntheses ◽  
Active Constituents ◽  
Mass Spectral ◽  
Growth Inhibitory

Further investigation of the South African tree Combretumcaffrum (Combretaceae) for murine P388 lymphocytic leukemia (PS) cell-growth inhibitory substances has led to discovery of three new active constituents designated combretastatins A-2 (5a, PS ED50 0.027 μg/mL), A-3 (5b, PS ED50 0.026 μg/mL), and B-2 (3b, PS ED50 0.32 μg/mL). Both combretastatins A-2 and A-3 were found to markedly inhibit tubulin polymerization. The structure of each combretastatin was firmly established by a combination of high resolution (400 MHz) 1H and 13C nuclear magnetic resonance and mass spectral analyses followed by total syntheses. The conversion of methyl gallate (7b) to combretastatin A-2 via intermediates 7c → 7d → 7e → 7a and 6a → 5a illustrates the practical synthetic route utilized for obtaining these substances. The Wittig reaction employed as the penultimate step in obtaining combretastatins A-3, afforded predominantly the natural Z isomer.

Cell growth inhibitory dihydrophenanthrene and phenanthrene constituents of the african tree Combretum caffrum

1988 ◽  
Vol 66 (3) ◽  
pp. 406-413 ◽  
Author(s):  
George R. Pettit ◽  
Sheo Bux Singh ◽  
Margaret L. Niven ◽  
Jean M. Schmidt
Keyword(s):  
Leukemia Cell ◽  
Crystal Structure Analysis ◽  
Lymphocytic Leukemia ◽  
Leukemia Cell Line ◽  
Spectral Studies ◽  
Mass Spectral ◽  
Growth Inhibitory ◽  
The Family ◽  
Lymphocytic Leukemia Cell ◽  
Combretum Caffrum

Combretum caffrum, a tree in the family Combretaceae, has been found to contain three 9,10-dihydrophenanthrenes (6,7-dihydroxy-2,3,4-trimethoxy; 7-hydroxy-2,3,4,6-tetramethoxy; and 2,7-dihydroxy-3,4,6-trimethoxy) that inhibit (ED50 2.2, 2.8, and 2.6 μg/mL) growth of the murine lymphocytic leukemia cell line. One phenanthrene (7-hydroxy-2,3,4,6-tetramethoxy) was also isolated with similar (ED50 2.0 μg/mL) activity. Structures for each of these substances, including a dihydrophenanthrene (2-hydroxy-3,4,6,7-tetramethoxy-9,10-dihydrophenanthrene), were determined by detailed high resolution nuclear magnetic resonance and mass spectral studies and (or) X-ray crystal structure analysis.

An Elegant Synthetic Route to 3-Cyano-5,6-dihydro-2-ethoxy-4-phenyl-pyrido[2,3-a]carbazoles

2004 ◽  
Vol 59 (1) ◽  
pp. 106-108 ◽  
Author(s):  
Isravel A. Danish ◽  
Karnam J. R. Prasad
Keyword(s):  
Elemental Analysis ◽  
Spectral Methods ◽  
Title Compound ◽  
Sodium Hydride ◽  
Synthetic Route ◽  
Mass Spectral ◽  
Plausible Mechanism

Abstract 2-Benzylidene-1-oxo-1,2,3,4-tetrahydrocarbazoles (1a - e) obtained from the corresponding 1- oxo-1,2,3,4-tetrahydrocarbazoles on reaction with malononitrile in dry benzene with sodium hydride afforded 3-cyano-5,6-dihydro-2-ethoxy-4-phenyl-pyrido[2,3-a]carbazoles (2a - e) in good yields. A plausible mechanism for the formation of the title compound has been proposed and all the compounds were characterised by IR, NMR, mass spectral methods and elemental analysis.

scholarly journals The Efficient Synthesis of Azasugars from Pentoses

2021 ◽  
Author(s):  
◽  
Michael Meijlink
Keyword(s):  
Clinical Trials ◽  
Biological Properties ◽  
Protecting Groups ◽  
Synthetic Route ◽  
Efficient Synthesis ◽  
Atom Economy ◽  
Total Syntheses ◽  
Structural Analogues ◽  
Original Procedure ◽  
Synthetic Routes

<p>Azasugars [e.g., 1-deoxy-aza-xylopyranose (1) Figure 1] are structural analogues of sugars [e.g., α-D-xylopyranose (2)] where the ring oxygen is substituted by a nitrogen atom. The resemblance of azasugars to their carbohydrate counterparts gives them various biological properties, such as the inhibition of glycosidase and glycosyltransferase enzymes, and as such, these compounds have been in clinical trials for the treatment of AIDS, diabetes,and cancer. Synthetic routes to azasugars have often involved the use of protecting groups, and therefore have generally reduced efficiency by requiring additional steps to apply or remove protecting groups or requiring adjustment of stereochemistry during the synthesis. This thesis presents the first example of a synthesis of four sterochemically different piperidine triols through a four-step methodology minimising the use of protecting groups starting from pentoses. The synthesis of D-xylose derived (3R,4r,5S)-piperidine triol was previously obtained in 40% yield over five steps, but was afforded in 45% overall yield over four steps using the methodology described within this thesis. Next, D-ribose derived (3R,4s,5S)-piperidine triol was obtained in 40% overall yield over four steps, which afforded a vast improvement on the previous most efficient synthetic route obtaining the azasugar in 24% yield over four steps. This four-step three-pot methodology has thus allowed for the synthesis of these piperidine triols in overall yields ranging from 4-69%, surpassing previous total syntheses in efficiency and improving overall atom economy. To further probe the applicability of the methodology, N-alkyl analogues (such as butyl-, phenylethyl-, and hydroxyethyl-analogues) of all four different piperidine triols were synthesised in comparable or greater overall yields compared to literature reports without any required adaptation to the original procedure. Included in these N-alkyl analogues are seven novel azasugars which were obtained in overall yields ranging from 6-35%.</p>

scholarly journals New Galloyl Derivative from Winged Sumac (Rhus copallinum) Fruit

2012 ◽  
Vol 7 (1) ◽  
pp. 1934578X1200700 ◽  
Author(s):  
Hang Ma ◽  
Tao Yuan ◽  
Antonio González-Sarrías ◽  
Liya Li ◽  
Maxwell E. Edmonds ◽  
...  
Keyword(s):  
Malic Acid ◽  
Betulinic Acid ◽  
Dimethyl Ester ◽  
Human Colon ◽  
Methyl Gallate ◽  
Mass Spectral Data ◽  
Antiproliferative Effects ◽  
Mass Spectral ◽  
Rhus Copallinum ◽  
Hct 116

Twelve compounds were isolated from Winged Sumac ( Rhus copallinum) fruit and their structures were elucidated on the basis of NMR and mass spectral data. The isolates included a new galloyl derivative, (R)-galloyl malic acid dimethyl ester (1), and eleven known compounds, gallic acid (2), methyl gallate (3), glucogallin (4), methyl m-digallate (5), methyl p-digallate (6), quercetin (7), myricetin (8), rhamnazin (9), kaempferol (10), betulinic acid (11), and oleanolic acid (12). All of the compounds were evaluated for antiproliferative effects against human colon tumorigenic (HCT-116, Caco-2) and non-tumorigenic (CCD18-Co) cell lines.

scholarly journals Antimitotic effect of the retinoid 4-oxo-fenretinide through inhibition of tubulin polymerization: a novel mechanism of retinoid growth–inhibitory activity

2009 ◽  
Vol 8 (12) ◽  
pp. 3360-3368 ◽  
Author(s):  
Valentina Appierto ◽  
Paola Tiberio ◽  
Elena Cavadini ◽  
Patrizia Casalini ◽  
Graziella Cappelletti ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Tubulin Polymerization ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Antimitotic Effect

Isolation and structure of rolliniastatin 1 from the South American tree Rolliniamucosa

1987 ◽  
Vol 65 (6) ◽  
pp. 1433-1435 ◽  
Author(s):  
George R. Pettit ◽  
Gordon M. Cragg ◽  
Judith Polonsky ◽  
Delbert L. Herald ◽  
Animesh Goswami ◽  
...  
Keyword(s):  
Crystal Structure ◽  
West Indies ◽  
Lymphocytic Leukemia ◽  
Life Extension ◽  
South American ◽  
The West ◽  
Medical Practices ◽  
American Variety ◽  
X Ray ◽  
Mass Spectral

Rolliniamucosa (Annonaceae), known in primitive medical practices of Indonesia and the West Indies as a treatment for tumors, has been investigated employing the seeds from a South American variety and the murine P388 lymphocytic leukemia (PS) for bioassay. The principal antineoplastic constituent (PS, 28% life extension, at 0.25 mg/kg and ED504.5 × 10−5 μg/mL) was found to be a new bis-tetrahydrofuran designated rolliniastatin 1. Structural elucidation of rolliniastatin 1 was accomplished by a combination of high resolution nuclear magnetic resonance (300 MHz), mass spectral, and X-ray crystal structure techniques.

scholarly journals Synthesis of Natural Products and the Development of Synthetic Methodology: The Case Study of (–)-Atrop-abyssomicin C

2017 ◽  
Vol 12 (8) ◽  
pp. 1934578X1701200
Author(s):  
Filip Bihelovic ◽  
Bojan Vulovic ◽  
Radomir N. Saicic
Keyword(s):  
Natural Products ◽  
Synthetic Route ◽  
Synthetic Methodology ◽  
General Applicability ◽  
Total Syntheses ◽  
New Methods ◽  
Naturally Occurring

During our attempt to follow the planned synthetic route to the naturally occurring antibiotic (–)- atrop-abyssomicin C, we encountered two shortcomings, which forced us to reconsider our tactics and find new methods to overcome the problems. These methods turned out to be of general applicability, as demonstrated later in total syntheses of two other natural products: (+)-allokainic acid and (-)-gabosine H. The paper provides a brief account of these endeavors.

A Synthetic Route to the MT1-MMP Inhibitor Ancorinoside D

Synthesis ◽  
2018 ◽  
Vol 51 (03) ◽  
pp. 730-738
Author(s):  
Rainer Schobert ◽  
Markus Petermichl ◽  
Christine Steinert
Keyword(s):  
Methyl Ester ◽  
Uronic Acid ◽  
Wittig Reaction ◽  
Synthetic Route ◽  
Acid Metabolite ◽  
Keto Ester ◽  
Mmp Inhibitor ◽  
Dieckmann Condensation ◽  
Neutral Conditions ◽  
Mediated Oxidation

A methyl ester of ancorinoside D, a 3-acyltetramic acid metabolite of a sponge Penares sollasi, was synthesised in ten steps starting from a protected β-d-glucopyranosyl-(1→4)-d-galactopyranosyltrichloroacetimidate donor. Its attachment to the left half of the 3-acyl spacer by a Schmidt glycosylation, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation to the uronic acid, introduction of the Z-alkene via Wittig reaction, and functionalisation of the spacer terminus with Meldrum’s acid gave a β-keto ester that reacted with dimethyl N-methyl-d-aspartate under neutral conditions to afford a fully protected ancorinoside D as the product of an unusual domino N-acylation–Dieckmann condensation. Global deprotection left a methyl ester of ancorinoside D, which resisted all saponification attempts.

Total Syntheses of (−)- and (+)-Boronolide and Their Plant Growth-Inhibitory Activity

2012 ◽  
Vol 76 (9) ◽  
pp. 1708-1714 ◽  
Author(s):  
Satoshi YAMAUCHI ◽  
Yasuyoshi ISOZAKI ◽  
Hiroki NISHIMURA ◽  
Tomoko TSUDA ◽  
Hisashi NISHIWAKI ◽  
...  
Keyword(s):  
Plant Growth ◽  
Inhibitory Activity ◽  
Total Syntheses ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

Isolation and structure of the unusual Indian Ocean Cephalodiscusgilchristi components, cephalostatins 5 and 6

1989 ◽  
Vol 67 (10) ◽  
pp. 1509-1513 ◽  
Author(s):  
George R. Pettit ◽  
Yoshiaki Kamano ◽  
Claude Dufresne ◽  
Masuo Inoue ◽  
Nigel Christie ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Indian Ocean ◽  
Cell Line ◽  
South African ◽  
Inhibitory Activity ◽  
Lymphocytic Leukemia ◽  
Two Dimensional ◽  
P388 Cell ◽  
The Indian Ocean

The Indian Ocean (South African) marine worm Cephalodiscusgilchristi (Hemichordata phylum) has been found to contain a series of unusual disteroidal alkaloids, designated the cephalostatins, that possess exceptionally potent lymphocytic leukemia (murine P388) cell line inhibitory activity (to ED50 10−9 μg/mL). Two of the less prominent members with P388 ED50 10−3–10−2 μg/mL, cephalostatins 5 (2) and 6 (3), were isolated and assigned structures based on rigorous interpretation of two-dimensional 400-MHz 1H and 13C nuclear magnetic resonance. Keywords: cephalostatins 5 and 6, disteroidal alkaloids, lymphocytic leukemia, cytostatic, Cephalodiscusgilchristi.

Sign in / Sign up

Export Citation Format

Share Document