Syntheses of natural products and biologically active compounds

6 Syntheses of Natural Products and Biologically Active Compounds 

Applications of the Heck reaction in natural-product syntheses were rather limited in the first 20 years, in spite of the great potential of this reaction for a wide scope of arylations 

Since the Heck reaction tolerates a variety of functionalities, extensive use of protecting groups can be avoided, and thus many highly functionalized target molecules can be assembled in just a few highly efficient steps. The frequently employed elevated reaction temperatures, which may be detrimental to the yield, can be avoided, if necessary, by an appropriate choice of special additives and/or leaving groups (cf. Sections 3.2.4 and 3.2.5). 

A total synthesis of morphine (240) employing a palladium-catalyzed coupling in a key step started from the hydroisoquinoline derivative 238 to give dihydrocodeinone 239 

Although a reasonable working hypothesis has been established for the mechanism of the palladium-catalyzed arylation and alkenylation of alkenes (the Heck reaction), individual 

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The addition of doubly deprotonated HYTRA to achiral4 5 as well as to enantiomerically pure aldehydes enables one to obtain non-racemic (3-hydroxycarboxylic acids. Thus, the method provides a practical solution for the stereoselective aldoi addition of a-unsubstituted enolates, a long-standing synthetic problem.7 As opposed to some other chiral acetate reagents,7 both enantiomers of HYTRA are readily available. Furthermore, the chiral auxiliary reagent, 1,1,2-triphenyl-1,2-ethanediol, can be recovered easily. Aldol additions of HYTRA have been used in syntheses of natural products and biological active compounds, and some of those applications are given in Table I. (The chiral center, introduced by a stereoselective aldol addition with HYTRA, is marked by an asterisk.)... 

Syntheses of natural products and biologically active compounds. .. 139... 

The remarkable efficiency of Shiina lactonization, which was mediated by acyl-transfer catalysts with MNBA, has been already demonstrated in a variety of successful total syntheses of natural products and biologically active compounds by other researchers (totaling over 370 citations to date). Furthermore, over 900 successful reactions using MNBA have been reported for the preparation of a variety of substrates including ester, amide, and lactone moieties. 

Total Syntheses of Natural Products and Biologically Active Compounds by Transitlon-Metal-Catalyzed C-C Cleavage... 

Since the first report on aldol additions of the chiral acetate 173, the reagent has been applied frequently in syntheses of natural products and biologically active compounds. In the course of these synthesis, it was noticed by several research groups that the extremely low temperatures are not always necessary and the diastereoselectivity in the aldol addition is only slightly diminished when the reactions are run at -78 °C or higher temperature. Among the applications of the acetate S) or (5 )-174 are inter alia y-amino-P-oxy-butanoic acid ( GABOB )... 

Modem acetylene chemistry plays a critical role in the current world-wide efforts to synthesize new molecular and polymeric carbon allotropes as well as carbon-rich nanomaterials. It is rapidly becoming clear that the preparative challenges in this interdisciplinary research area at the interface between materials science and chemistry are formidable and rival those in the more established synthesis of natural products and biologically active compounds. Modern materials research strongly relies on advanced synthetic methodology, and it is hoped that the field will attract many synthetically oriented chemists into its ranks their efforts will be rewarded by the development of materials with unique properties and unprecedented applications. 

In this chapter, applications of amidine, guanidine and phosphazene superbases to the synthesis of natural products have been discussed. Many structurally complex natural products have been synthesized efficiently and elegantly by making use of the reactions described. Currently, much attention is focussed on the development of chiral superbases and their application to asymmetric reactions. Such catalytic asymmetric reactions are expected to offer exciting and efficient new approaches to the synthesis of natural products and biologically active compounds. 

Table 3-9 Syntheses of important natural products and biologically active compounds involving the Heck reaction (HR) (Figures 3.2 and 3.3)...

Natural products and biologically active compounds synthesized by use of the HYTRA aldol method. 

Baxendale [53]. As such, complex natural products and biologically active compounds could be obtained in a fully automated sequence without the use of conventional workup procedures examples are the flow syntheses of several casein kinase I inhibitors [54], imatinib base (Gleevec) [55], oxomaritidine [56], and grossamide [57]. One limitation of this strategy is the need to replace the cartridges after the reagents have been consumed. 

This review summarizes advances in the chemistry of acridines pubfished mainly in the last decade. As more than 1000 pubhcations on acridines appear every year, this review cannot be comprehensive. It presents recent, selected examples of acridines as natural products, as biologically active compounds, some apphcations of technically or biotechnicahy interesting acridines, examples of recendy described syntheses of acridines, and some reactions on the acridine ring. 

The transition metal cross-couplings of allenes described here offer practical solutions for the modification of 1,2-dienes and access to the preparation of highly functionalized 1,3-dienes, alkynes and alkenes, which are often not easily accessible in a regio- and stereoselective manner by classical methods. Some of the prepared alkynes or functionalized allenes serve as important intermediates in syntheses of natural products, biologically active compounds, e.g. enynes and enyne-allenes, and new materials. It can be predicted that further synthetic efforts will surely be focused on new applications of allenes in transition metal-catalyzed cross-coupling reactions. 

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