Synthesis Nicolaou

Nicolaou s Synthesis. Nicolaou s synthesis also involves a B-ring closure to connect the A and C rings.33 The retro synthetic approach is depicted in Scheme 7-59. 

Uemura, T., Zhang, X.Y., Matsumura, K., Sayo, N., Kumobayashi, H., Ohta, T., Nozaki, K. and Takaya, H. J. Org. Chem., 1996, 61, 5510 a classical example is the Monsanto synthesis of (l)-DOPA using ruthenium complexed with the diphosphine DIPAMP, see Classics in Total Synthesis, Nicolaou, K.C. and Sorensen, E.J. VCH, Weinheim, 1996. 

Palladium-Catalyzed Cross-Coupling Reactions in Total Synthesis Nicolaou, K.C. Bulger, P.G. Sarlah, D. Angew. Chem. Int. Ed. 2005, 44, 4442. 

In what can only be regarded as a marathon of oligosaccharide synthesis, Nicolaou et al. have achieved a synthesis of six rhynchosporosides (217), which are members of a family of fungal... 

Unlike most Grob fragmentations, reactions in which the nucleofuge and electrofiige are not tethered yield three product molecules. Several groups have exploited this strategy in synthesis. Nicolaou designed a novel... 

In his second synthesis, Nicolaou used a chiral enolate of type 10 which contained the (S)-configuration at C3 and the required oxidation level at Cl. However, again almost no selectivity was observed in the aldol coupling... 

As an instance of the use of unusual elements in synthesis, Nicolaou etal. have applied selenium chemistry to the preparation of sulphur-containing analogues (21 X = S) of prostaglandin I2 as shown in Scheme 4. This group has also synthesized the carba-analogues (21 X = CH2) of prostaglandin I2. 

Joys of molecules. 1. Campaigns in total synthesis. Nicolaou, ICC. (2005), J. Org. Chem., 70, 7007-7027. Chasing molecules that were never there Misassigned natural products and the role of chemical synthesis in modern structure elucidation. Nicolaou, K.C., Snyder, S. A. (2005), Angew. Chem. Int. Ed., 44, 1012-1044. Recent advances in natural product synthesis by using intramolecular Diels-Alder reactions. Takao, K.-I., Munakata, R., Tadano, K.-I. (2005), Chem. Rev., 105, 4779-4807. 

In the last fifteen years macrolides have been the major target molecules for complex stereoselective total syntheses. This choice has been made independently by R.B. Woodward and E.J. Corey in Harvard, and has been followed by many famous fellow Americans, e.g., G. Stork, K.C. Nicolaou, S. Masamune, C.H. Heathcock, and S.L. Schreiber, to name only a few. There is also no other class of compounds which is so suitable for retrosynthetic analysis and for the application of modem synthetic reactions, such as Sharpless epoxidation, Noyori hydrogenation, and stereoselective alkylation and aldol reactions. We have chosen a classical synthesis by E.J. Corey and two recent syntheses by A.R. Chamberlin and S.L. Schreiber as examples. 

Nicolaou and co-workers established the severely strained A-ring oxazole (21) in their total synthesis of antitumor agent diazonamide A through initial oxidation of the hindered alcohol of intermediate 20 with TPAP and subsequent Robinson-Gabriel cyclodehydration of the resultant ketoamide with a mixture of POCI3 and pyridine (1 2) at 70°C. ... 

The generality of the dioxahorolane method makes it well-suited for synthesis of complex natural products. For example, Nicolaou et al. have successfully used... 

Nicolaou group initiated a program directed towards their total synthesis.2. ... 

Through a display of a series of electrocyclization reactions, the Nicolaou group demonstrated the biomimetic , one-step synthesis of the endiandric acids involving the cascade of reactions proposed by Black. The polyunsaturated compounds 37 and 38 (Scheme 7) were designed for their relative stability and potential to serve as... 

Nicolaou, K.C. Petasis, N. A. Selenium in Natural Products Synthesis, CIS Philadelphia, 1984. 

A distinguishing feature of the Nicolaou synthesis of rapamycin is the use of a palladium-mediated tandem inter-/intramolecular Stille coupling to construct rapamycin s 31-membered macrolide ring and conjugated triene moiety. This maneuver was unprecedented in the macrolide field,9 and it can be applied to a fully deprotected seco substrate (vide infra). 

Scheme 19. The Sonogashira coupling in Nicolaou s synthesis of (12S)-HETE (78).

Using Kishi s modification of the Suzuki coupling procedure,45 Nicolaou et al. accomplished the convergent union of compounds 112 and 113 (see Scheme 28).38b 46 This coupling is the key step in a synthesis of (55,6/ )-dihydroxyeicosatetraenoic acid [(55,6/ )-diHETE] methyl ester (115). Importantly, the configurations of the two coupling partners are reflected in the Suzuki coupling product 114. 

Scheme 28. Nicolaou s synthesis of (5S,6fi)-diHETE methyl ester (115).

Our general survey of palladium in organic synthesis must now come to an end. At the very least, we hope that our brief foray into this fascinating area conveys some of the vitality that characterizes research in this area. The remainder of this chapter will address the first total synthesis of rapamycin by the Nicolaou group. This work is predicated on a novel variant of the Stille reaction. 

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