Baeyer-Villiger antibiotic

Erythronolide B, the biosynthetic progenitor of the erythromycin antibiotics, was synthesized for the first time, using as a key step a new method for macrolactone ring closure (double activation) which had been devised specifically for this problem. Retrosynthetic simplification included the clearance of the stereocenters at carbons 10 and 11 and the disconnection of the 9,10-bond, leading to precursors A and B. Cyclic stereocontrol and especially the Baeyer-Villiger and halolactonization transforms played a major role in the retrosynthetic simplification of B which was synthesized starting from 2,4,6-trimethylphenol. 

Baeyer-Villiger oxidation has been used to selectively oxidize one of two methyl ketones (to esters) in the final step of a stereoselective synthesis of (—)-acetomycin, an antibiotic with potential anti-leukemia activity (equation 25)135. This reaction was accomplished using MCPBA as oxidant, with an excess of sodium bicarbonate and 5-/er/-bulyl-4-hydroxy-2-melhyl phenyl sulfide as a radical inhibitor. 

In the synthesis of the following lactones, the oxygen atom has been introduced by Baeyer-Villiger rearrangement, e.g. ( )-phoracantholide I [137], ( )-lactone antibiotic A26771B [138], exaltone [139]. 

The efficiency of this method was demonstrated in a total synthesis of the antibiotic (-r)-tetrahy-drocerulenin 28 (Scheme 8) and (-h)-cerulenin [11]. Irradiation of complex 22 in the presence of the chiral iV-vinyl-oxazolidinone 24, which is easily prepared from the amino carbene complex 23 [12], leads to the cyclobutanone 25 with high diastereoselectivity. Regioselective Baeyer-Villiger oxidation followed by base-induced elimination of the chiral carbamate yields the butenolide 26 in high enantiomeric purity. This is finally converted, using Nozoe s protocol [13], to the target molecule 28 by diastereo-selective epoxidation (- 27) and subsequent aminolysis. 

Alder reaction, catalysed by dimethylaluminium chloride, has been employed in a new total synthesis of pseudomonic acids A and C from hexa-1,5-diene. In a further study of the ionophore antibiotic lasalocid (3), it has been subjected to Mannich and Baeyer-Villiger reactions. The former took an unusual course in that the carboxyl was replaced by an aminomethyl group. The natural ionophore X-14547A (4) has been synthesized from two separately prepared segments (5) and (6) of the molecule. ... 

TBS-Protected D-lactaldehyde 961 is used as the chiral source for the synthesis of jS-lactam 969, a key intermediate in the synthesis of the antibiotic monobactam Aztreonam [254] (Scheme 131). The cmcial step in the synthesis, the reaction of A/-trimethylsilylimine 962 with the lithium enolate of STABASE (963), affords ra 5-j5-lactam 964 with 98% diaster-eoselectivity. Desilylation, Jones oxidation, and Baeyer—Villiger oxidation provides acetoxy jS-lactam 968, which in itself is a useful intermediate for the preparation of j5-lactam anti-... 

Chiral a-methylene-y-butyrolactones An asymmetric synthesis of a-methylene- y-butyrolactones such as 7 utilizes the benzoate (2) of (1R,2S)-1, which on reaction with 1,1-dibromohexane and Zn-TiCL TMEDA forms the (Z)-enol ether 3. Thus this product reacts with dichloroketene to form the cyclobutanone (—)-4. Baeyer-Villiger oxidation of 4 followed by oxidation with chromium(Il) perchlorate provides the a-chlorobutenolide (+)-5. Hydrogenation and oxidation provides the 8-carboxy-y-butyrolactone (-) 6. The final step involves introduction of a methylene group to provide (-)-7, methylenolactocin, a natural antitumor antibiotic. 

L-Quebrachitol has been converted in several steps into derivative 43, a known intermediate for the synthesis of the polyene antibiotics restricticin and restric-tinol. The key step involved a Baeyer-Villiger oxidation of a ketone-containing derivative. ... 

The production of antibiotics and steroids is mainly based on the Baeyer-Villiger oxidation. This synthetic route is an oxidative transformation of carbonyl compounds using a strong oxidant such as a peroxyacid. The transformation of an acyclic ketone to an ester is shown by the following scheme ... 

Baeyer-Villiger oxidative ring expansion of myo-inositol derivatives 81 and 82 provides the -lactones 83 and 84 respectively, which are used as intermediates in a convogent synthesis of the antibiotic natural product polyoxin J (Scheme 21 - also see Chapter 19). ... 

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