Of pseudomonic acid

Scheme 1.13. Cationic domino process in the synthesis of pseudomonic acid C analogue.

Some older examples of this type of process include the studies of Marko on the synthesis of pseudomonic acid C analogues [118], the preparation ofindanones by Snider [119], and synthesis of the skeleton of the sesquiterpenes khusiman and zi-zaen by Wenkert and Giguere and their coworkers [120, 121]. 

Hughes, J., and Mellows, G. (1980). Interaction of pseudomonic acid A with Escherichia coli B isoleucyl-tRNA synthetase. Biochem. J. 191, 209—219. 

Analogous addition of a sugar radical to an unsaturated sulfone has been described by the same authors in the course of pseudomonic acid synthesis. For this, UV irradiation of the iodosugar was used to generate a secondary radical [120],... 

G. E. Keck and A. M. Tafesh, Free-radical addition fragmentation reactions in synthesis A second generation synthesis of (+)-pseudomonic acid C, J. Org. Chem. 54 5845 (1989). 

D. P. Curran, An approach to the enantiocontrolled synthesis of pseudomonic acids via a novel mon-Claisen rearrangement, Tetrahedron Lett. 23 4309 (1982). 

D. P. Curran and Y. Suh, Synthetic applications of a substituent controlled Claisen rearrangement. Preparation of advanced intermediates for the synthesis of pseudomonic acid, Tetrahedron Lett. 25 4179 (1984). 

Dihydropyrane synthesis." A novel synthesis of a dihydropyrane intermediate (2) for a synthesis of pseudomonic acid (3) involves an ene reaction of formaldehyde with a 1,4-diene, followed by a quasi intramolecular Diels-Alder reaction with formaldehyde as dienophile, both reactions being catalyzed by ethylaluininum dichloride. Thus, reaction of 1 with CH20 (3 equiv.) and C2H5A1C12 (4.5 equiv.) gives 2 in 35-40% yield via a number of intermediates. 

Tetrahydropyrans 182, formed by this process, proved to be highly valuable intermediates for the synthesis of 2,3,4,6-tetrasubstituted tetrahydropyrans. Indeed, the exo-methylene double bond can be easily transformed, with high stereocontrol, into a variety of useful functionalities. For example, Marko et al. used this approach during the total synthesis of pseudomonic acid analogue (Scheme 13.65) [49]. 

In a clever piece of work, Snider et al. have used a quasi intramolecular carbonyl Diels-Alder cycloaddition to produce a key intermediate for syntheses of pseudomonic acid A (175) (Scheme 20). Thus a Lewis acid catalyzed ene reaction of alkene (170) and formaldehyde afforded (171), which com-plexed with additional formaldehyde to give (172). Intramolecular [4 + 2] cycloaddition of (172) gave adduct (173) which produced dihydropyran (174) upon hydrolysis. 

Application of Claisen methodology led to a number of successful total syntheses of natural compounds. Thromboxane B2 has been synthesized from a 4,5-unsaturated sugar derived from D-glucose [126]. The Ireland-Claisen rearrangement [127] is also the key reaction used to control the introduction of the right wing of pseudomonic acids [128]. 

Fleet, G W J, Shing, T K M, Enantiospecific synthesis of (35 -hydroxy-25 -methyl) butyl triphenylphosphonium iodide a precursor for the chiral side chain of pseudomonic acid. Tetrahedron Lett., 24, 3657-3660, 1983. 

H. H. Baer and Z. S, Hanna, The preparation of amino sugars and branched-chain sugars by palladium-catalysed allylic substitution of alkyl hex-2-enopyranosides. Can. J. Chem. 59 889 (1981). D. P. Cuiran, An approach to the enantiocontrolled synthesis of pseudomonic acids via a novel mon-Claisen rearrangement. Tetrahedron Lett. 23 4309 (1982). 

The reduction of the p-acyloxy sulfone is most often carried out with sodium amalgam, as the examples below indicate. The reductive elimination can be buffered with disodium hydrogenphosphate for sensitive substrates. In certain applications it has proven advantageous to utilize lithium or sodium in ammonia. For example, Keck s synthesis of pseudomonic acid C made use of the lithium/ammonia reductive elimination to simultaneously form an alkene and deprotect a benzyl ether.In studies directed toward the same target, Williams made use of a reductive elimination procedure developed by Lythgoe, involving the formation of the xanthate ester followed by reduction with tri-n-butyltin hydride. ... 

The Julia coupling can be utilized as an alternative to the Schlosser-Wittig reaction to form ( )-al-kenes. Several reported syntheses of pseudomonic acid C (385) have provided interesting clues as to variability of tq)plications of the Julia coupling in the context of natural product synthesis. 

Keck attempted to apply the Julia coupling to the synthesis of pseudomonic acid Despite the success of the sulfone (393) in reactions with simple aldehydes, only modest yields of the desired coupling were observed. This problem was solved by reversing the aldehyde (395) and sulfone components (394), as shown in Scheme 55. The anion was formed with LDA in THF and condensed with the aldehyde. The P-hydroxysulfone was converted to the mesylate, and the reduction and simultaneous deprotection of the benzylglycoside was carried out with lithium and ammonia to produce the ( )-alkene (396), in 37% overall yield with excellent selectivity. 

The use of divergent intermediates allowed the rapid synthesis of a diverse collection of compounds, four examples of which are shown at the bottom of Figure 2. Although the best showed some inhibition of ITRS from plants, none had significant activity in the glasshouse. The left-hand side-chain of pseudomonic acid A bears some resemblance to isoleucine, and it has been speculated that it binds at the isoleucine... 

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