Pseudomonic acid esters synthesis

Boeckman and coworkers studied the reaction of bis(thmethylsilyl) ester (361) with aldehydes to form the silyl-substituted unsaturated ester (362 equation 86). The anion was formed with potassium or lithium diisopropylamide. Other metals, such as magnesium or aluminum, were introduce by treating the lithium anion with Lewis acids. The addition step produced a single diastereomer, en ling the effects of counterion and steric bulk on the elimination to be ascertained. Excellent selectivity for the ( )-isomer (362) may be obtained by using K or Li cations and a sterically hindered aldehyde. In studies directed toward the synthesis of substituted pseudomonic acid esters, the Peterson alkenation was utilized to form a mixture of (Z)- and ( )-alkene isomers, one example of which (365) is depicted in equation (87). In this example the conditions were optimized to form the highest degree of selectivity for the (Z)-alkene. 

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... 

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. ... 

Protoporphyrin II dimethyl ester, 77 Pseudomonic acid, 115 Pseudotropane, 81 Push-pull dienes, 149 Pyrazine, 320 Pyrazole, 311 Pyrazolone, 170 Pyridazine, 313-317 Pyridine, 2, 302, 312-313 product, 310 substituted, 146, 245 synthesis, 60 Pyridinium salt, 311... 

In the total synthesis of pseudomonic acid C, Barrish et al. used the rearrangement of ester 45 as a key step [26]. With the (Z)-configured ester 45 the anti-product was obtained nearly exclusively (> 95% ds), while the corresponding ( )-ester showed a much lower diastereoselectivity. 

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