Natural products synthetic analogues from

The stereoselective synthesis of carbohydrates from acyclic precursors is a research topic that has attracted considerable attention over the past decadeT Efforts in this area are easily justified and have maximum impact particularly when directed toward rare sugars or other polyhydroxylated molecules that are not conveniently accessed via classical "chiron" approaches.2 An underlying theme of such efforts, of course, is the development of practical synthetic methodology that will find broad application in the enantio- and diastereoselective synthesis of natural products, their analogues, and other compounds of biological interest. 

M. Elliott, Synthetic Insecticides Related to Natural Pyrethrins , in Crop Protection Agents from Nature natural products and analogues , ed. L.G. Copping, Royal Society of Chemistry, Cambridge, UK, 1996, pp. 254-300. 

Whitney, J.M., Parnes, J.S., and Shea, K.J. (1997) Total synthesis of a Plocamium monoterpene marine natural product - synthetic applications of bridgehead allylsdanes./. Org. Chem., 62, 8962-8963. Mohan, S.K. and Meryala, H. (2001) Synthesis of acyclic marine halogenated natural product analogues from myrcene. Asian J. Chem., 13, 881-886. 

The main challenge for chemists in this area is to provide an analogue from DHA in the shortest number of chemical steps to make the drug economically viable for the treatment of malaria. The following section will describe the chemistry behind the synthesis of semi-synthetic analogues of the natural product, some of which have much improved pharmacological profiles. 

Since the discovery of triazole formation from phenyl azide and dimethyl acetylenedicarboxylate in 1893, synthetic applications of azides as 1,3-dipoles for the construction of heterocychc frameworks and core structures of natural products have progressed steadily. As the 1,3-dipolar cycloaddition of azides was comprehensively reviewed in the 1984 edition of this book (2), in this chapter we recount developments of 1,3-dipolar cycloaddition reactions of azides from 1984 to 2000, with an emphasis on the synthesis of not only heterocycles but also complex natural products, intermediates, and analogues. 

Several compounds of this type, formally derived from aldoses by oxidation of the terminal CH2OH group to -CHO, have been prepared. Dialdoses arise as intermediates in structural studies, but they are also valuable starting materials for synthetic conversions, in particular for natural-product synthesis. A branched-chain dialdose, streptose (167), occurs as a component of the antibiotic streptomycin. The structure of streptose was elucidated after extensive investigations of its derivatives and transformation products.371 The 2,5-dimethoxytetrahydrofuran fulvanol (168), an analogue of apiose, has been isolated from the plant Hemerocallis fulva 12... 

Fig. 2. Analogues of the spirotryprostatins from Danishefsky s synthetic program, with cytotoxicities 5000 times higher than those of the natural products.

The antitumor activity displayed by camptothecin (28) and its analogues has led to a great deal of interest in such compounds.36 Camptothecin is a complicated alkaloid to isolate, and analogues, which are of biological interest, are synthesized from the natural product itself.37 This need to access a wide range of analogues has led to a need for synthetic studies directed toward the development of a concise, yet inexpensive, total synthesis of camptothecin. 

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