Natural products total synthesis" publications

A recent publication by the group of Baran reports the total synthesis of ageli-ferin, an antiviral agent with interesting molecular architecture (Scheme 4.16) [42], Just 1 min of microwave irradiation of sceptrin, another natural product, at 195 °C in water under sealed-vessel conditions provides ageliferin in 40% yield, along with 52% of recovered starting material. Remarkably, if the reaction is performed without... 

The first total syntheses of epothilones A and B were published by the groups of Danishefsky [49] and Nicolaou [83] only shortly after publication of the absolute stereochemistry of the natural products. Various other (formal) total syntheses followed, in which many different approaches and reaction types were used. Also, a variety of analogues was synthesized and even libraries were created [9, 84]. Several reviews on the properties and synthesis of epothilones and derivatives have been published [9-13]. 

Since the first publication, amine-catalyzed Diels-Alder reactions of a,/ -unsaturated aldehydes have been investigated in much detail [15, 26-33]. Catalyst immobilization studies on solid support [26, 27], as well as in ionic liquids [29], have shown advantages for amine recycling, while partially maintaining good levels of asymmetric induction [34]. The use of this reaction in total synthesis has allowed the rapid preparation of (+)-hapalindole Q, a tricyclic alkaloid natural product containing four contiguous stereocenters (Scheme 3.2) [28]. 

To obtain a supply of this natural product for biological and preclinical development and in an attempt to develop derivatives for SAR, various groups soon began work toward the synthesis of peloruside A. This resulted in a number of notable publications on the partial synthesis250 259 and three total synthesis by De Bradander,260 Taylor261 and Ghosh.262 In addition, one review of the synthetic methods, microtubule stabilisation and computational analyses of peloruside A has been completed recently.263... 

A measure of the interest in the biological activity of these dibenzyl-butyrolactone lignans is evinced in the recent spate of publications dealing with the total synthesis of the natural optically active products. Again, the Stobbe condensation pathway (Scheme 9) has been usefully exploited for this purpose. In a series of papers, resolution of the intermediate hemisuccinate esters (433 by chiral bases has been described (54), as has asymmetric hydrogenation (55), and the optically active lignan products synthesized in the usual way (42 - 44 45). 

Alpine borane (the Midland reagent, 3) has found broad use in the synthesis of complex natural products. As early as 1980, only one year after Midland s seminal publication, Johnson and co-workers used 3 for the reduction of ketone 18 to afford alcohol 19 in 75% yield and 97% ee.12 This material was used to complete the synthesis of 20, a cyclization precursor in Johnson s total synthesis of hydrocortisone acetate. 

It is striking that Diels and Alder finally received the Nobel Prize in chemistry in 1950, more than two decades after their initial publication. The science of total synthesis of natural products was slow to advance and was hindered by World War II. These factors perhaps explain the delay in fuUy appreciating the impact of the Diels-Alder reaction. The modem era of total organic synthesis is generally considered to have started during the 1940s. In 1952, Robert Bums ( R. B. ) Woodward (1917-79) at Harvard would employ the Diels-Alder reaction to brilliant effect en route to total syntheses of the steroids cortisone and cholesterol. 

In a series of publications, Nicolaou and coworkers have demonstrated the utility of DMP for the selective oxidation of 4-substituted anilides 894 to p-quinones 895 and 2-substituted anilides 896 to < -azaquinones 897 (Scheme 3.360) [1289-1291], The first process was applied to the short, efficient total synthesis of epoxyquinomycin B [1290], while the second type of oxidation allowed rapid access to complex analogs of pseudopterosin and elisabethin natural products [1291],... 

The Total Synthesis of Natural Products, Vol. 9 Simon, J. A. Ed. Wiley-Interscience Publication, J. Wiley and Sons, New York, p. 1. 

Once the attractive structure of epibatidine and its interesting pharmacological properties became known, there appeared a plethora of publications on the synthesis of the racemic natural product. [563] Over the years, also a few enan-tioselective total syntheses have been developed, two of which are discussed here. 

Our interest in the polyoxin group of antibiotics [50] was focused on the nature of polyoximic acid [51], a deceptively simple azetidine carboxylic acid derivative which had eluded the efforts of synthetic chemists [52] since the original publication of the structure. Only recently was a synthesis reported for /rnatural product based on low field NMR stupes [51]. A total synthesis of this acid in our laboratory [54,55], and comparison of NMR spectra with a sample kindly provided by Professor Isono showed that they were different. The sample of the naturally-derived amino acid was suitable for X-ray analysis (even after 20 years of isolation and storage ), and it proved to be ci5-polyoximic acid [54]. A new synthesis of this isomer was undertaken and confirmed its structural as well as stereochemical identity (Scheme 9) [55]. TTie stereochemical revision of polyoximic acid could... 

Total Synthesis. The complexity of azadirachtin can best be illustrated by the number of academic groups, and publications, aimed at the total synthesis of this molecule (28-39). Despite this massive effort, over nearly a decade, no synthesis is near completion. At this point, the only progress has been in model studies approaching the furopyran, I (28-35), and decalin, II (36-38), portions of the molecule. Completion of this work is still years away, and when finished will furnish azadirachtin costing orders of magnitude more than the natural product. 

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