Sarcodictyin libraries

One of the first reported solid-phase syntheses of a nonoligomeric natural product was that of lavendustin A.31 This compound is a potent tyrosine kinase inhibitor. Fortunately, the structure of this material is highly amenable to synthesis and elaboration on a solid phase. In fact, the synthesis was reported by a researcher working alone on this project (Green).31 

The indolyl diketopieprazine family of natural products includes the fu-mitremorgins, verruculogens, and cyclotryprostatins 68. A solid-phase syn- 

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Structure/activity relationship studies on the sarcodictyin library are performed by induction of tubulin polymerization and by cytotoxicity studies with three cancer cell lines, including Taxol-resistant lines. Derivatives that induce tubulin polymerization more strongly than the natural product sarcodictyin have been determined, and can show higher cytotoxicity even as far as Taxol-resistant tumor cells are concerned. The results of the structure/... 

Nicolaou, K.C. et ah, Solid and solution phase synthesis and biological evaluation of combinatorial sarcodictyin libraries, J. Am. Chem. Soc., 120, 10814, 1998. 

For building up a library around a given core structure many examples have been given, e.g. an Indolactam library by Waldmann et al. [11], a Sarcodictyin-based library by Nicoloau et al. [12] and a Taxoid library by Xiao et al. [13]... 

One of the earliest researchers in the area of natural product-like libraries is K.C. Nicolaou. Inspired by the total synthetic efforts of his group on many important natural product targets and coupled with his interest in synthetic methodology and chemical biology, Nicolaou reported a number of elegant examples (see Chapter 11) that include natural product-like libraries based upon Taxol, " sarcodictyins, epothiolones, vancomycin, muscone, and psammaplin a. ... 

Jagtap, P.G. et al.. Design and synthesis of a combinatorial chemistry library of 7-acyl, 10-acyl, and 7,10-diacyl analogs of pacUtaxel (taxol) using solid phase synthesis, J. Nat. Prod., 65, 1136, 2002. D Ambrosio, M., Guerriero, A., and Pietra, R, Sarcodictyin A and sarcodictyin B, novel diterpenoidie alcohols esterified by ( l-Alll-methylurocanic acid isolation from the Mediterranean stolonifer... 

Nicolaou et al. have prepared a library of 22 Sarcodictyin-analogs by attaching core structure 2 onto solid phase using polymer-bound Wittig-ylide 1 (Scheme 1) [74]. The OH-groups of the core scaffold were decorated by alkylation or converted to carboxylic acid or amino functionalities which could be derivatized as esters, carbamates, or secondary amines. Cleavage off the soUd phase was performed via trans-ketalization, a reaction step which was exploited to increase the diversity by using different kind of alcohols. 

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