Synthesis challenges

The novel structure of cylindrospermopsin, with a guanidine embedded in a tricyclic system, six chiral centers, and polar sulfate, uracil and guanidine functional groups, makes its synthesis challenging. Its potent toxicity makes the synthesis of cylindrospermopsin an important problem that has been the subject of intense interest.1,7 8... 

Though the mode of action of bromethalin [61] is not known, it has been determined that it is not an anticoagulant as flocoumafen is. The presence of four bulky groups ortho to the tertiary nitrogen makes its synthesis challenging. Bromethalin synthesis involves introducing one or more of the ortho bulky groups after the formation of diphenylamine (Fig. 16) [62],... 

This section describes the early history leading to creation of the steroid industry, provides an account of key processes used in the manufacture of the oral contraceptives and anti-inflammatories currently marketed in the United States and highlights the creation of diverse biological activities by molecular manipulation of the steroid molecule. The section concludes with an outline of a few of the synthesis challenges faced and overcome in the manufacture of betamethasone anti-inflammatories. 

Bile acids were the logical starting point for the manufacture of cortisone in the late 1940s, but steroids from plant sources, and particularly diosgenin ex yams, were gaining credibility as time passed. The chemical synthesis challenges associated with each of these raw materials are outlined in Scheme 7. 

Organic Synthesis Challenging Natural Products and New Frontiers... 

Figure 3. Synthesis challenges facing the use of polypeptides as biomaterials.

Jeon I, Lee D, Krauss U et al (2009) A new model for the presentation of tumor-associated antigens and the quest for an anticancer vaccine a solution to the synthesis challenge via ring-closing metathesis. J Am Chem Soc 131 14337-14344... 

This thesis focuses on the total synthesis of Maoecrystal V. Maoecrystal V, a natural product with potent biological activity, is a novel diterpenoid which was isolated from the leaves of Chinese medicinal herb, Isodon eriocalyx, by Prof. Handong Sun and co-workers. The synthesis challenge exists in the novel pentacyclic ring system and six chiral centers, including four continuous chiral centers, three all quaternary carbon centers. 

Historically, the stimulus for the development of a particular reaction has been interconnected vith a class of natural products vhose synthesis vould be greatly facilitated by the use of that particular bond construction. For example, the steroid synthesis challenges proved instrumental in the development of the Diels-Alder reaction. So too the synthesis challenges associated vith the macrolide antibiotics have provided the motivation for the development of the full potential of the aldol addition reaction. R. B. Wood vard s 1956 quote on the hopelessly complex architecture of the erythromycins vas probably stimulated, in part, by the fact that the aldol reaction existed in a completely underdeveloped state five decades ago. 

What makes this particular synthesis challenging to analyze To construct a cyclic product, we must connect the malonate a-carhon to two functionalized atoms of a single substrate molecule, in this case the l-bromo-5-chloropentane. The five carbon atoms of this compound combine with the a-carbon of the malonate to furnish the desired six-memba-ed ring. 

Actinides. Monocyclopentadienyl derivatives are less common and the majority of the reported complexes are Lewis-base adducts of the type CpAnXs-Ln (X = halide). Their steric and electronic unsaturation make their synthesis challenging. The first CpUCl3 2L compounds in ethereal solvents (DME or THF) were prepared by reacting UCI4 with thallium cyclopentadienide (Marks and Ernst 1982). 

Lend, E., Menchi, G., Trabocchi, A., 2016. Carbohydrates in diversity-oriented synthesis challenges and opportunities. Org. Biomol. Chem. 14 (3), 808-825. 

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