Pseudomonic acid, synthesis

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],... 

APPLICATION OF LEWIS ACID CATALYZED QUASMNTRAMOLECULAR DIELS-ALDER REACTION TO PSEUDOMONIC ACID SYNTHESIS. 

Figure 7. Preparation of 22, a key intermediate for pseudomonic acid synthesis, by Lewis acid catalyzed ene and quasi-intramolecular Diels-Alder reactions.

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]. 

A microwave assisted Comforth rearrangement of oxazole-4-carboxamides 106 efficiently afforded 5-aminooxazole-4-carboxylates 107. This procedure was applied to the formal synthesis of a natural antibiotic derived from pseudomonic acid <06TL4698>. 

The rearrangement provides a stereocontrolled synthesis of the C-pyranoside 2, present in pseudomonic acids.2... 

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). 

Many antibiotics, which inhibit protein synthesis, do not bind to ribosomes but block any of a variety of vital chemical processes needed for growth. Among them are pseudomonic acid, which inhibits isoleucyl-tRNA synthetase from many gram-positive bacteria.1111/VV Rapamycin, best known as an immunosuppressant (Box 9-F), inhibits phosphoinositide-3-kinase and also phosphorylation of the cap-binding protein 4G, a component of the eukaryotic initiation factor complex (Fig. 29-11 ).ww The bacterial enzyme peptide deformylase, which is absent from the human body, has been suggested as a target for design of synthetic antibiotics. 01... 

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]. 

The use of iodoetherification has been exploited in the synthesis of precursors to mono- and bis-THF acetogenins,234 potent antitumor and pesticides. Also, has been used in the synthesis of tetrahydrofuran analogs of precursors to pseudomonic acid.235 As well, N1S has been used as the iodine source, for example in the synthesis of other acetogenins.236 Other compounds synthesized via iodocyclization include ( )-(a)-multistriatin,237 ( )-velbanamine, and ( )-isovalbanamine,238 and (+)-citreoviral.239... 

Marko et al. employed an enantioselective Noyori BINAL-H reduction in the synthesis of methyl monate C (11), the methyl ester derivative of the potent antibiotic pseudomonic acid C6 (Scheme 4.3e). The a,(3-unsaturated ketone 12 underwent the Noyori reduction with the (S)-BINAL-H reagent to give the product desired (13) in 70% yield and 95% ee. The chiral alcohol was then condensed... 

The cleavage of acyclic acetals by N-bromosuccinimide was discovered in 1951.128 The reaction was subsequently extended to cyclic derivatives129 but its synthetic potential was not fully realised until Hanessian applied the method to carbohydrate benzylidene acetals to give bromo benzoate esters.130 A noteworthy feature of the transformation is that it can be performed on a 100 g (or larger) scale [Scheme 374],131-132 The reaction has been exploited in the synthesis of a number of natural products such as Monensin,133 Pseudomonic acid,134 Boromycin,135 Thienamycin.136 and Rifamycin.137 Williams and co-workers42... 

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