Divergent total synthesis

MCRs have been recognized as valuable tools in the preparation of diversity-oriented synthesis (DOS) and divergent total synthesis (DTS), for the construction of low molecular weight compound libraries through combinatorial strategies and parallel synthesis, and for rapid access to namral product and drug-like small molecules with complex and diverse molecular structures [12], Thus, in 2011, Van der Eycken and coworkers reported a microwave-assisted diastereoselective Ugi-4C-3CR... 

Lee, Kiyoun Boger, Dale Total Syntheses of (-)-Kopsifoline D and (-)-Deoxoapodine Divergent Total Synthesis via Late Stage Key Strategic Bond Formation J. Am. Chem. Soc. 2014, DOI 10.1021/ja500548e... 

Further elaboration on the oxidation states of diene bicycle 75 provided the divergent total synthesis of corianin (78), picrotoxinin (79), and picrotin (80) in less than half the number of steps previously reported. 

SCHEME 13.30 Utilization of an axinellamine intermediate (153) for a divergent total synthesis of massadine (chloride). TFA counterions have been omitted for clarity. 

Thus, an efficient and convergent total synthesis of ( )-isocembrene has been accomplished in seven steps from the known geranylacetone through an intramolecular Stille cross-coupling reaction. The strategy is of great potential for the divergent synthesis of complex cembrane-type diterpenoids such as cembrene-C and sarcophytols. 

McDevitt, R E, Fraser-Reid, B, A divergent route for a total synthesis of cyclophellitol and epicyclophellitol from a [2.2.2]oxabicyclic glycoside prepared from D-glucal, J. Org. Chem., 59, 3250-3252, 1994. 

As described above, the divergent asymmetric total S3mtheses of cemuane- and quinolizidine-t3q)e Lycopodium alkaloids were accomplished. The first asymmetric total synthesis of cemuine (86) was achieved starting from the easily available (+)-citronellal in 9.6% overall yield in 21 steps. Furthermore, we have succeeded in the syntheses of cermizine D (90), cermizine C (87), cermizine C A-oxide (88), and senepodine G (89) from common key intermediate 91, and have established an efficient synthetic route to cemuane- and quinolizidine-t3q)e Lycopodium alkaloids. 

Although we opened this chapter by stating that total synthesis played a minimal role in modem structure elucidation, at this point it now constituted the only tool that could finally prove if the structure of diazonamide A was indeed 1. As we shall see, it took just a few months to put this problem to rest, as the Nicolaou group at The Scripps Research Institute was ultimately able to develop not one, but two, completely divergent routes to this revised structure (1) which verified its accuracy. These endeavors are the focus of the remainder of this chapter. 

Collective total synthesis has been gathering more and more attention recently. Prof Jieping Zhu s divergent synthesis toward five members of Aspidosperma alkaloids represent one of the most recent advancement (Fig. 14.14) [49]. The advantages in Prof Zhu s synthesis plan include (i) to construct the indole unit at a late stage of the synthesis instead... 

Garg NK, Caspi DD, Stoltz BM. Development of an enantio-divergent strategy for the total synthesis of (-1-)- and (—)-dragmacidin F from a single enantiome of quinic acid. J. Am. Chem. Soc. 2005 127 5970-5978. 

Also, the figures contain nephelometric curves for the product t (that is, for p + s, in the proportions formed in the synthesis) and the fraction o, which was also a thermally precipitating product and deposited onto the walls of the reaction vessel in the course of the copolymerization of NVC1 with NVIAz at their initial molar ratio of 85 15 (Table 1). One can see that the precipitation behaviour of the total product t differs, although the amount of the s-fraction is almost the same at 31-33%. Obviously, this depends on the properties of the s-fraction. For instance, the heat-induced precipitation of the sample t formed from the feed with a comonomer molar ratio of 90 10 (Fig. 3b) is suppressed by the presence of its own s-fraction to a markedly lesser extent when compared to the product t obtained at the comonomer molar ratio of 85 15 (Fig. 3a). Most likely, such differences reflect the divergent influence of the s-fractions on the coagulation processes in the thermo-precipitating fractions of the total product t. These differences, for example different surface... 

For the divergent synthesis, the reaction sequence is amidification/chlorida-tion. Once the polychloride of the acid is obtained, a partial or total amidifica-tion reaction with an amino alcohol yields a MIM, which is either ionic or nonionic, respectively. 

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