No abstract

: Asymmetric total syntheses of Taxol and of 8-demethyltaxoids 24-27 from the 8-membered ring compounds 29 and 12 respectively were completed via successive formation of the BC ring system by intramolecular aldol reaction, then the ABC ring system utilizing an intramolecular pinacol cyclization. The conversion of the tricyclic compound 43 to 7-TES baccatin III (49) was carried out by way of a newly devised method of constructing the oxetane ring. The dehydration condensation between a derivative of Nbenzoylphenylisoserine and 49, followed by deprotection afforded the antitumor agent Taxol.Key words : Taxol; 8-demethyltaxoids; 8-membered ring compounds; intramolecular aldol reaction; intramolecular pinacol cyclization; oxetane formation; dehydration.Taxol, substance isolated from the Pacific yew tree, has been found to have an anti-cancer effect, and the synthesis of its complex structure has been a tempting challenge for synthetic chemists over the past decades. 1)In 1994, two groups succeeded in the chemical total synthesis of Taxol: in Holton's strategy, (-)-camphor was used as the starting material, and the synthesis of the complex structure of Taxol was achieved by a,sequence of many highly effective synthetic reactions,2~ whereas in Nicolaou's convergent approach, the key step of B ring closure reaction was carried out after constructing the connected A and C ring systems.3~ In 1995, Danishefsky reported a total synthesis according to a convergent strategy by way of intramolecular Heck cyclization.4~ Recently, Wender accomplished a total synthesis by a linear strategy using fragmentation of an epoxy-alcohol derived from a-pinene.5~In our strategy, the synthesis of the basic skeleton of Taxol was planned to start from the chiral B ring intermediate 29, prepared via optically active polyoxy-unit 8, and to proceed by constructing the A and C ring systems onto this framework (Fig. 2). This novel strategy offers a flexible synthesis of the B ring system of Taxol and its analogues from chiral linear precursors,6),7)Commercially available neopentyl glycol (1) was converted to aldehyde 2 via its benzylideneacetal. An asymmetric aldol reaction between 2 and the requisite ketene silyl acetal promoted by Sn(OTf)2 coordinated with chiral diamine gave the desired optically active ester 3 in good selectivity (anti/syn=79121, anti aldol; 93% ee). The ester 3 was converted to aldehyde 4 as shown in Fig. 3.The chiral aldehyde 4 was also prepared by the Antitumor agent Taxol.

A new method for the total asymmetric synthesis of antitumor agent Taxol is described. Baccatin III, a complex carbon framework, is synthesized by way of B to BC to ABC ring construction. Further, a method of forming Taxol from baccatin III and a β‐amino acid is also demonstrated.

An efficient systematic approach to the diversity-oriented synthesis of polyketides has been developed to provide both skeletal and stereochemical diversity. Each synthetic intermediate is also a desired polyketide fragment and no protecting group manipulations are required. A first-generation synthesis provides a 74-membered polyketide library comprising six different skeletal classes, each in one to five steps from propargylic alcohol precursors. A study of epoxyol opening reactions revealed unusual reactivity trends based on epoxide configuration.Polyketide natural products exhibit a tremendous variety of biological activities and chemical structures, making them attractive starting points for the synthesis of natural product-based libraries. 1 Biologically, polyketides are known to bind to a wide range of targets and, thus, can be considered an empirically 'privileged' family of structures. 2 Chemically, polyketides present significant challenges in diversity-oriented synthesis, in that flexible, highly efficient synthetic approaches are required to allow systematic modification of biologically active compounds identified from the resulting libraries. oriented synthesis would provide access to a wider range of skeletal motifs found in polyketide natural products. Indeed, generating libraries with both skeletal 5 and stereochemical diversity 6 is a key current challenge in diversity-oriented synthesis. 7 Toward these ends, we report herein a unified approach to the diversity-oriented synthesis of polyketides and a first implementation that provides 74 stereochemically diverse polyketides falling into six different structural classes.At the outset of our efforts, we noted that the polyketide skeleton arises biosynthetically from reiterative couplings of simple malonate building blocks, with tailoring reactions generating most of the structural diversity, primarily through variations in oxidation state and stereochemical configuration. 8 We envisioned a conceptually related synthetic approach in which simple precursors are transformed stereoselectively to a variety of polyketide structures through formal alterations in oxidation state, with each synthetic intermediate also representing a desired polyketide fragment. Such an approach can be considered 'biomimetic' under Breslow's original broad definition. 9 Importantly, in contrast to polyketide total synthesis, in which a variety of synthetic approaches can be interchanged as necessary, diversity-oriented synthesis requires that these various polyketide motifs be accessed in a unified, systematic fashion.Thus, we formulated the general synthetic strategy outlined in Scheme 1, using propargylic alcohols 3 as versatile synthetic precursors 10 that could be transformed to a variety of polyketide structures. These key intermediates could be generated from α-alkoxycarbonyl compounds 1and alkynes 2, potentially bearing R 1 and R 3 substituents. Terminal benzyl ether and dimethyl acetal groups were selected as functionalities that are directly compatible with...