Tricolorins

The synthesis of the disaccharide subunit 85 of tricolorin A, a cytotoxic resin glycoside isolated from lpomoea tricolor, provides a unique opportunity to compare the efficiency of an RCM-based macro cyclization reaction with that of a more conventional macrolactonization strategy. Furthermore, this specific target molecule challenges the compatibility of the catalysts with various functional groups. 

Two trisaccharide macrolactones have been characterized from the aerial parts of Ipomoea tricolor Cav. (syn. Ipomoea violacea L.) (heavenly blue), namely, tricolorins... 

Fig. 3. Graphical representation of a unit cell showing the presence of 18 water molecules in the asymmetric unit in addition to the four independent tricolorin A (106) molecules...

Fig. 4. Superposition of the four independent molecules of tricolorin A (106) showing that the internal trisaccharide subunit has limited conformational freedom due to its macrolactone structure...

Fig. 5. Two different views (ca. 180°) of a single tricolorin A (106) molecule. Left, hydrophilic face. Right, hydrophobic face. Protons of hydroxyl groups are colored in cyan...

Notable in the tricolorin A (106) solid state is the presence of 18 water molecules in the unit cell, and an anisotropic repartitioning of the hydrophobic and hydrophilic sections. The water molecules form a dense network that creates a dividing layer between the hydrophilic faces (see Fig. 6). The high water content indicates that the conformation in the solid state is not dominated by intermolecular forces and could be indicative of a similar conformation in both solution and supermolecular... 

Fig. 6. Anisotropic repartitioning of the hydrophobic and hydrophilic interfaces observed m the crystal packing arrangement of tricolorin A (106)...

RCM was also employed as a key design element for the synthesis of tricolorin A (106). This novel strategy demonstrated the efficiency of macrocyclizations using the standard ruthenimum catalysis either by the classical Grubbs carbene complex or the recently developed cationic ruthenium aUenylidene complex as the... 

The cytotoxic potential of several resin glycosides has been evaluated against mammalian cancer cultured cell lines. For tricolorin A (106), the most potent cytotoxic activity (ED q 2.2 pg/cm ) was observed with human breast cancer and... 

Pereda-Miranda R, Mata R, Anaya AL, Wickramaratne DBM, Pezzuto JM, Kinghom AD (1993) Tricolorin A, Major Phytogrowth Inhibitor from Ipomoea tricolor. J Nat Prod 56 571... 

Bah M, Pereda-Miranda R (1996) Detailed FAB-Mass Spectrometry and High Resolution NMR Investigations of Tricolorins A-E, Individual Oligosaccharides from the Resins of Ipomoea tricolor (Convolvulaceae). Tetrahedron 52 13063... 

Brito-Arias M, Pereda-Miranda R, Heathcock CH (2004) Synthesis of Tricolorin F. J Org Chem 69 4567... 

Fiirstner A, Muller T (1998) Metathesis Route to Resin Glycosides Formal Total Synthesis of Tricolorin A. J Org Chem 63 424... 

Hernandez R, Vuelvas A, Garcia A, Fragoso M, Pereda R, Ibarra C, Rojas A (2008) Calcium-Dependent Effect of Tricolorin A on Intestinal and Arterial Smooth Muscle Contractility. 7th Joint Meeting of AFERP, ASP, GA, PSE and SIE. Planta Med 74 973... 

Achnrne L, Pereda-Miranda R, Iglesias-Prieto R, Moreno-Sanchez R, Lotina-Hennsen B (1999) Tricolorin A, a Potent Natural Uncoupler and Inhibitor of Photosystem II Acceptor Side of Spinach Chloroplasts. Physiol Plant 106 246... 

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